To assess the safety profile, pharmacokinetics, pharmacodynamics andpreliminary antitumour activity of fixed-dose SHR-1210, a novel anti-PD-1antibody, in advanced solid tumours.A total of 36 patients with advanced solid tumours receivedintravenous SHR-1210 at 60 mg, 200 mg and 400 mg  until disease progression or intolerable toxicity.The concentration of SHR-1210 was detected for pharmacokinetics, and receptoroccupancy on circulating T lymphocytes was assessed for pharmacodynamics.No dose-limiting toxicities were observed. Maximum administered dosewas not reached. Most adverse events were grade 1 or 2. Treatment-related severeadverse events were found in two patients. No treatment-related death wasreported. Two complete responses  and sevenpartial responses were seen. In responders, the median follow-up time was 16.0months (range 8.3–19.5), and the median duration of response was not reached(range 2.7–17.5+ months). The half-life of SHR-1210 was 2.94 d, 5.61 d and 11.0 dfor 3 dose levels, respectively.Our results demonstrated a promising antitumour activity and amanageable safety profile of SHR-1210, displayed an explicit PK evidence of thefeasibility of fixed dose, and established the foundation for furtherexploration. To the best of our knowledge, there are no phase 1 clinicaltrials evaluating the efficacy of anti-PD-1 antibodies at fixed dose.Monoclonal antibodies are usually given based on the body weight,which has recently been re-evaluated because of the specific properties, and theincreased convenience and improved safety of the administration paradigm of fixeddose.Based on this consideration, we initiated this phase 1 trial(NCT02742935) of PD-1 blockade with a novel humanised high-affinity IgG4-kappamonoclonal antibody SHR-1210 in 36 patients with advanced solid tumours, assessingthe safety profile, preliminary antitumour activity, PK and receptor occupancy (RO)rate at fixed doses, establishing the feasibility of this dosing strategy and thebasis for further clinical expansion.Eligible patients had documented advanced solid tumours; an agebetween 18 and 75 years old; an Eastern Cooperative Oncology Group (ECOG)performance status of 0 or 1 ; had experienced PD orrecurrence after at least one systemic treatment for advanced or metastaticdisease; at least one measurable lesion according to Response Evaluation Criteriain Solid Tumors (RECIST) (version 1.1); adequate haematologic, hepatic and renalfunction. Patients with brain metastasis were enrolled only when the lesions hadbeen stable for at least 3 months. Patients with a history of or active autoimmunedisease, a concomitant secondary cancer, history of organ transplantation orPD-1/PD-L1 treatments, active hepatitis B or C viral infection, or ongoingsystemic immunosuppressive therapy were excluded. Previous cancer treatment,radiotherapy or radiosurgery must have been completed at least 4 weeks before theenrolment. All patients provided written informed consent before theenrolment.This multicenter, single-arm, open-label, phase 1 clinical trial wasapproved by the institutional review board and independent ethics committee of theNational Cancer Center, Cancer Hospital, Chinese Academy of Medical Sciences. Itwas conducted in accordance with the Declaration of Helsinki and the internationalstandards of good clinical practice. Informed consents had been obtained frompatients.This study consisted of an initial dose-escalation and subsequentexpansion phase. During dose-escalation, patients were treated with SHR-1210 at afixed dose of 60 mg every 2 weeks, with escalation to 200 and 400 mg. We chosethese dose levels mainly based on the PK and toxicity properties of SHR-1210 givenin previous phase 1 study conducted in Australia in 2015. Meanwhile, 200 mg Q3W ofother anti-PD-1 antibodies, such as Pembrolizumab and Nivolumab, have both beenconfirmed to have promising efficacy and tolerability in several tumours and havebeen approved in worldwide. Based on these information and significant efficacysignal in the 60 mg cohort, the dose escalation did not proceed beyond 400. Aquantity of 400 mg was the preplanned maximum administered dose. The drug wasadministered as an intravenous infusion at week 1, week 5, and then every 2 weeks.The first cycle  was designed for observation of dose-limitingtoxicity (DLT), which was defined as ≥grade 2 uveitis, ≥grade 2 interstitialpneumonia, ≥grade 3 non-haematologic and ≥grade 3 haematologic adverse events(AEs) related to study medications occurring during the first cycle. Doseescalation proceeded when 3 patients had completed the safety observation periodat a given dose level without any DLT, otherwise 3 extra patients were required atthis dose level, and if the 3 extra patients developed DLT, the dose escalationterminated, the dose prior to which was defined as maximum-tolerated dose (MTD).Intra-patient dose escalation was not permitted. A modified definition of DLT wasincorporated in the study’s protocol. Delayed DLT such as severe immune-relatedAEs was also recorded for safety analysis after the first 4 weeks, but notinfluencing the dose escalation. No escalation was continued after 400 mg groupeven if no DLT was observed.On the basis of initial signals of activity, subsequent expansioncohorts of extra 9 patients each were enrolled at 60, 200 and 400 mg. Alltreatments were to continue until intolerable toxicity, confirmed diseaseprogression, death or withdrawal of consent. Treatment beyond initial diseaseprogression (PD) was allowed in clinically stable patients  at the discretion of the investigator.Safety evaluation, including clinical examination and laboratoryassessments were conducted for all patients treated with SHR-1210 at baseline andregular intervals. Notably, the laboratory assessments for endocrine function wererepeated every 4 weeks, while the liver and kidney function tests repeated every 2weeks. SHR-1210 administration could be interrupted or delayed forprotocol-defined reasons, but dose modification was not permitted. The severity ofall AEs was graded according to the National Cancer Institute Common TerminologyCriteria for Adverse Events (NCI CTCAE), version 4.03. General AEs were handledbased on established safety guidelines. Specific AEs, such as immune-related AEswere handled according to the study protocol, as well as those clinical routinelyused guidelines. Patients could receive the treatment again after the AEsrecovered to initial state or grade 1. Severe adverse event (SAE) was defined asany event lead to death, life threaten, hospitalisation or prolongedhospitalisation, forever or severe deformity or dysfunction, innate abnormalitiesor birth defect and other vital medical events deteriorating the patient’sdisease.Independent radiologic evaluation by CT or MRI was done at baselineand every 8 weeks during the first 6 months, and every 12 weeks thereafter.Overall response rate (ORR) was summarised as the proportion of response-evaluablepatients who had a best response of complete response (CR) or partial response(PR), based on RECIST, version 1.1, as assessed by independent radiologists.Disease control rate (DCR) was defined as the proportion of CR, PR and stabledisease (SD) patients.The concentration of SHR-1210 was detected for PK studies. Plasmasamples for SHR-1210 PK analysis were collected at −0.5 h, 5 min (±2 min), 2 h(±5 min), 6 h (±5 min), 24 h (±5 min), 48 h (±30 min), day 8 (±60 min), day 15(±60 min), day 22 (±60 min) from the initiation of drug in Cycle 1, and −0.5 h,5 min (±2 min) from drug administration on day 1 and day 15 from Cycle 2. Sampleswere stored at −80 °C until measurement. Serum concentrations of SHR-1210 weredetermined using a validated enzyme-linked immunosorbent assay (ELISA) by Covance(Shanghai) with a lower limit of quantification (LLOQ) of 157 ng/mL. Thebioanalytical method validation of the ELISA was performed based on the FDA’srecommendation, including the validation of “Calibration Standards”, “QualityControls Intra and Inter Assay Bias and Precision”, “Quality Control Samples”,“Selectivity”, etc. Anti-PD-1 antibody was obtained from Sino Biological andanti-human IgG (Fab specific) peroxidase antibody produced in goat was obtainedfrom Sigma-Aldrich. RO on circulating T lymphocytes was assessed forpharmacodynamics studies. The plasma samples for pharmacodynamics studies werealso collected at above-mentioned time points expect for 5 min (±2 min) from drugadministration on day 1 and 15 from Cycle 2. RO of SHR-1210 was determined as theratio of CD45+/CD3+ cells after incubation with control IgG4 (in vivo bindingsites of SHR-1210) to that observed cells after incubation with SHR-1210 .11 For cases in which the tissue sample had notbeen optimally collected or prepared or in which PD-L1 expression could not beassessed, the PD-L1 status was categorised as unevaluable.We measured PD-L1 expression in pretreatment, archival tumoursamples with an investigational version of the Human PD-L1 ImmunohistochemistryKit using the 6E8 antibody .For each sample, the membrane expression of PD-L1 in tumour cells was determinedby two independent pathologists blinded to the clinical data. PD-L1 cell scoreswere generally based on a single section. All the neoplastic cells were scorable.PD-L1 positivity was defined as ≥5% of tumour cell membranestaining.All statistical tests for PK and correlative studies analyses useda two-sided significance level 0.05, adjusted for multiple comparisons. TheClopper-Pearson method was used to calculate the 95% CI for ORR. Theprogression-free survival (PFS) were estimated with the Kaplan–Meier method. PKand pharmacodynamics parameters of SHR-1210 were calculated usingnon-compartmental approaches by WinNonlin 5.3 software. SPSS statistics version 22software was used for all analyses.A total of 36 patients with advanced solid tumours, includingoesophageal squamous cell carcinoma (ESCC), gastric cancer, triple-negative breastcancer (TNBC), colorectal cancer, non-small-cell lung cancer (NSCLC),nasopharyngeal cancer (NPC), hepatocellular cancer, bladder cancer and cervicalcancer, were included between April 26, 2016 and December6, 2016. The median treatment duration was 3.2months (range 0.5–19.3), and eight patients remained on study treatment. A totalof 28 (77.8%) patients discontinued SHR-1210. The most common reason for treatmentdiscontinuation was disease progression (24/28). Two patients stopped SHR-1210because of lung infection that may not related to the study treatment. One patientdied from upper gastrointestinal haemorrhage, which thought to be related totumour progression. The other patient stopped SHR-1210 because of grade IVneutropaenia.The MTD was not reached, and no DLT (including delayed DLT) wasobserved in three dose groups. At the date of analysis, 35 patients 97.2%) hadexperienced at least one AE, and 32 (88.9%) of them were treatment-related AE(TRAE) (Table % hadexpTwo patients (5.6%) had treatment-related SAE. One patient withcervical cancer (200 mg) developed grade IV neutropaenia and thrombocytopenia,leading to the termination of treatment. The grade 4 neutropaenia appeared 12 daysafter the first dose of SHR-1210. The results of autoimmune antibodies tests wereall negative. Patient refused bone marrow aspiration. After continuous treatmentof granulocyte colony-stimulating factor and thrombopoietin, neutropaeniapersisted for 3 weeks and patient recovered without any signs of infection. Theother patient with ESCC (60 mg) experienced grade 1 elevation of troponin, leadingto hospitalisation and suspending of treatment. After coronary angiographyexcluding the possibility of myocardial infarction, he resumed SHR-1210 andresulted in sustained partial response.12 All the patients with hypothyroidism had nosymptoms and were successfully treated with replacement therapy. irAEs greaterthan grade 3 were observed in 2 patients (5.6%): grade 4 neutropaenia, anaemia andthrombocytopenia in one patient (2.8%); and grade 3 diarrhoea in the other patient(2.8%).Immune-related AEs (irAEs) were observed in 31 patients (86.1%),the most of which were reactive capillary hemangioma, pruritus, hypo- orhyperthyroidism, abnormal liver function test, diarrhoea and skin rash, etc. Mostof the irAEs were grade 1 or 2. The incidence of hypothyroidism in patients whohad normal thyroid function at baseline was 12.1% (4/33), which was similar tothat of other anti-PD-1 antibodies.Based on independent central review assessment, antitumour activitywas observed at all doses Fig. . TwopatAt the time of the data cutoff, 28 patients (77.8%) had diseaseprogression and 22 patients had died. The median PFS as assessed by independentreview and median OS were 1.8 months (95% CI: 1.6–2.0) and 9.8 months (95% CI:7.3–12.3), respectively. The Kaplan–Meier analysis estimated a 6-month PFS rate of38.4% (95% CI: 22.3–54.5) and a 6-months OS of 80.6% (95% CI: 67.7–93.5). Amongthe 28 patients who had progressive disease, progression occurred in preexistingtarget lesions (10 patients), new metastatic sites (3 patients), or both (15patients). There are no significant differences among 3 dose groups in terms ofPFS or OS.  of SHR-1210increased in a dose-dependent manner from 60 to 400 mg, ranging from 2.94 to 11.0days; similarly, Cmaxand AUC were also directly dose-dependent. After repeated doses, the accumulationratio of SHR-1210 at Cmin from C1D1 to C5D1 was 2.54–3.07 atsteady state (1st infusion in Cycle 5); whereas, the accumulation index at the endof infusion (Ceoinf)ranged from 1.08 to 1.53  after 1st infusion of Cycle 5 was 67,77 and 76% for 60, 200 and 400 mg, respectively.The PD-1 RO results indicate that SHR-1210 has high affinity toPD-1after a single-intravenous infusion, which is dose-dependent and with a meanpeak occupancy of 85%  , and progressivedisease for nine patients (six ESCC and two gastric cancer). Notably, the PD-L1expression of tumour-infiltrating mononuclear cells in the patient with gastriccancer who experienced complete response was relatively high (30%).To the best of our knowledge, this is the first study reporting theantitumour activity, safety and PK of SHR-1210, a novel anti-PD-1 antibody at afixed dose in heavily-treated patients with advanced solid tumours, indicating theclinical potential of SHR-1210 due to its promising antitumour activity and amanageable toxicity profile.4 The data of this phase I clinicaltrial demonstrated that 25% of the patients treated with all doses of SHR-1210 haddurable objectives responses. The ORR and DCR of ESCC was 21.4 and 42.9%, slightlyhigher than those treated with nivolumab reported in a phase II clinical trial .13 The ORR of stomach cancer, lung cancer, NPC, livercancer, bladder cancer was 20, 33.3, 33.3, 50, 100%, respectively, not completelyconsistent to the previous reported data,4 which may be explained by the limited samplesize, yet still providing a comparative clinical efficacy with other checkpointinhibitors. Notably, no responses or disease control could be observed intriple-negative breast cancer and cervical cancer. In the previously reportedclinical trials on immunotherapy in patients with breast cancer, immune checkpointinhibition like pembrolizumab and atezolizumab demonstrated a response rate of 18.5and 24%, respectively.15In terms of cervical cancer, the ORR of pembrolizumab in PD-L1 positive patients was17%, and the responses were long-lasting with a mean duration of 26weeks.16All these results should be interpreted with caution due to the unselected patientsregardless of PD-L1 expression and the small sample size in this study.The inhibition of PD-1 displays a wide spectrum of clinicalantitumour activity among multiple tumours.18Interestingly, two patients experienced PD after treatment of SHR-1210, followed bysubsequent remission or stable status after continuous treatment with the immunecheckpoint inhibitor. Response after initial progression, which would otherwise beclassified as PD by RECIST 1.1, is described as “pseudo-progression”. This achallenging phenomenon during immune checkpoint inhibitor treatment, as severalstudies had reported,20and that is why we need to confirm the response at least 4 weeks after the firstevaluation of PD, in order to avoid the premature termination of treatment becauseof pseudo-progression, offering the necessity of the combination or alteration ofresponse evaluation criteria from conventional RECIST 1.1 to immune-related responsecriteria (iRECIST).21In addition to the responses, durable objective responses were alsonoteworthy in multiple types of tumours. Within the median follow-up time of 10.1months, the median duration of response was not reached. The longest duration hasreached 17.5+ months, and the response was still lasting. The relativelylong-lasting duration of response was similar with those treated with pembrolizumaband nivolumab.22 suggesting this therapy could be delivered in anoutpatient setting. The most commonly reported AE was reactive capillary hemangioma, which appeared after the initiation of treatment and regressedspontaneously both during and after treatment. Despite the notably high incidence,no patients discontinued or postponed the treatment due to this AE. Although,immune-related skin events were not unexpectedly, reactive capillary hemangioma is arare phenomenon and has never been reported in other anti-PD-1 antibodiespreviously. The mechanism of capillary hemangioma was still under investigation,with a possible explanation of the imbalance between enhancers and inhibitors ofangiogenesis as several reports suggested.24 The investigation of the mechanism of capillaryhemangioma induced by SHR-1210 is ongoing.Most of the toxicities reported in this study were grade 1 or 2,which could be resolved with appropriate supportive treatment, and were consistentwith other previously reported anti-PD 1 antibodies,7 Aquantity of 200 mg Q3W of pembrolizumab has been confirmed to have comparableefficacy and tolerability in melanoma and NSCLC clinical trials. Based on PKproperties of given pembrolizumab either in weight-based or fixed doses, studiesdemonstrated that both dosing strategies were appropriate.25 With a similar maximal efficacyand acceptable tolerability, the administration of pembrolizumab at fixed dose wasapproved in NSCLC and head and neck squamous cell carcinoma in the UnitedStates,27 and is continuing to beinvestigated in trials for various indications. For SHR-1210 in patients withadvanced solid tumours, our results showed some correlation trends of patients’ bodyweight with PK properties of SHR-1210, but not with receptor occupancy rate.Meanwhile, the CV% for the exposure of SHR-1210, as shown in Table Another critical question this study brought up is that can anti-PD-1antibody at fixed-dose reach the comparable clinical efficacy with given based onbody weight. Dosing of therapeutic monoclonal antibodies is usually given based onbody weight. However, this traditional dosing paradigm has recently beenre-evaluated because of the specific properties and the increased convenience,elimination of wastage, improved safety, and improved compliance of fixeddose.28 and it’s one of the most vitalparameters to determine the recommended dose of the drug. Our data display that thedrug concentration could be basically maintained higher than 2000 ng/ml to realisesufficient RO saturation within 28 days after the initial infusion at a dose notlower than 200 mg. Based on the above-mentioned studies and analysis, SHR-1210 givenat a fixed dose of 200 mg could display a sufficient clinical efficacy and haveacceptable tolerance. Although, the frequency of administration requires clinicalsupport from further studies, the fixed dose of 200 mg could be the recommended dosein the further clinical expansion.The pharmacodynamics of SHR-1210 were assessed according to PD-1 ROon circulating T lymphocytes. The RO is an important factor to test whether the drugdevelops biological activity by determining whether the pathway leading toantitumour activity is effectively saturated,29A series of trials have enroled only patients with PD-L1 positivetumours.17 Our data also suggest apossible association between anti-tumour activity and higher PD-L1 expression ontumour cells, although the number of patients is too small to make definiteconclusions. It’s premature to assert the validity of PD-L1 as predictive biomarkerin patients treated with SHR-1210.Data from several studies suggested improved response of anti-PD-1antibodies in patients with PD-L1 positive tumours.In summary, our results demonstrated a promising antitumour activityand a manageable safety profile of SHR-1210 in pretreated patients with advancedsolid tumours, displayed an explicit PK and RO evidence of the feasibility of fixeddose, and determined the recommended dose of 200 mg.Supplementary Figure 1Supplementary Figure 2Supplementary Figure 3


Extracellular vesicles (EVs) play a central role in intercellular communication, which is relevant for inflammatory and immune processes implicated in neurodegenerative disorders, such as Parkinson’s Disease (PD). We characterized and compared distinctive cerebrospinal fluid (CSF)-derived EVs in PD and atypical parkinsonisms (AP), aiming to integrate a diagnostic model based on immune profiling of plasma-derived EVs via artificial intelligence. Plasma- and CSF-derived EVs were isolated from patients with PD, multiple system atrophy (MSA), AP with tauopathies (AP-Tau), and healthy controls. Expression levels of 37 EV surface markers were measured by a flow cytometric bead-based platform and a diagnostic model based on expression of EV surface markers was built by supervised learning algorithms. The PD group showed higher amount of CSF-derived EVs than other groups. Among the 17 EV surface markers differentially expressed in plasma, eight were expressed also in CSF of a subgroup of PD, 10 in MSA, and 6 in AP-Tau. A two-level random forest model was built using EV markers co-expressed in plasma and CSF. The model discriminated PD from non-PD patients with high sensitivity (96.6%) and accuracy (92.6%). EV surface marker characterization bolsters the relevance of inflammation in PD and it underscores the role of EVs as pathways/biomarkers for protein aggregation-related neurodegenerative diseases. A major current medical need in the field of neurology is the identification of reliable biomarkers in vivo for the diagnosis of neurodegenerative diseases. Parkinson’s Disease (PD) is the second most common neurodegenerative disorder of the elderly, characterized by the progressive loss of dopaminergic neurons in the substantia nigra . To dateExtracellular vesicles (EVs) are emerging as novel and sensitive biomarkers for neurodegenerative diseases ,5. EVs aIn a previous work, we demonstrated that distinctive pools of plasma-derived EV surface markers related to inflammatory and immune cells stratified patients with PD and AP according to the clinical diagnosis. We characterized distinctive EV subpopulations in plasma by simultaneously immunophenotyping 37 different membrane proteins using a flow cytometry multiplex bead-based platform ,13 and tTherefore, the aims of the present study were: (1) to characterize CSF-derived EVs in healthy subjects and patients with PD, MSA and AP-Tau; (2) to compare EVs profiling in matched CSF and plasma samples of PD and AP patients; (3) to improve our previous diagnostic model, based on plasma-derived EVs by integrating information provided by CSF-derived EVs immunophenotyping.A total of 16 patients, for which matched plasma and CSF samples were analyzed in the current study, made up the optimization cohort: 4 idiopathic PD, 4 probable MSA and 4 probable AP-Tau, among which 3 had probable progressive supranuclear palsy and 1 had possible corticobasal degeneration. The plasma discovery cohort included 84 subjects  9]. Sub. Sub9]. g at 10 °C, to eliminate cellular components; then, three consecutive centrifuges were performed to further purify the plasma, eliminating apoptotic bodies and larger EVs . We previously demonstrated no significant change in flowcytometric analysis by MACSPlex assay of plasma samples with and without EV enrichment by ultracentrifugation [In total, 10 mL of blood was collected into anticoagulant-EDTA tubes, after at least 4 h fasting. The following protocol was performed to obtain EV enriched plasma  Figure a: samplefugation . Samplesg at 4 °C). Pellets were resuspended in 30 µL of particle-free PBS. The storage period varied among samples according to the consecutive enrollment of subjects in the study, between 2015-07 and 2020-10.Five mL of CSF was collected into 15 mL polypropylene tubes, and immediately frozen a. After g at 4 °C. The obtained pellet was resuspended in 100 µL of particle-free PBS. A total of 1 µL of ultraconcentrated plasma or CSF was diluted in particle-free PBS—1:500 and 1:250, respectively. NTA analyses were performed as previously described [Nanoparticle concentrations and diameters were measured by NanoSight LM10  equipped with a 405 nm laser and Nanoparticle Tracking Analysis NTA 2.3 software . Only for NTA analysis, to rule out a confounding effect of ultracentrifugation on EV amount and diameter, plasma samples (100 µL) were centrifuged akin to CSF samples for 18 h at 100,000× escribed .The screening approach  was previously described ,13 and iIn total, 60 µL of plasma and 30 µL of ultracentrifuged CSF were added to the MACSPlex Buffer solution  and analyzed with MACSQuant Analyzer-10 flow cytometer . As a blank control we used MACSPlex Buffer incubated with beads and detection antibodies. Median fluorescence intensity (MFI) for each EV surface marker was normalized by the mean MFI for specific EV markers . All analyses were based on normalized MFI (nMFI) values. Samples were analyzed blind to the clinical diagnosis.Tests for the reliability/specificity of MACSPlex human Exosome Kit for EVs and for the technical consistency and reproducibility of the assay were performed in our previous work .Statistics was performed using IBM SPSS Statistics 22.0 , PYTHON 2.7 , and GraphPad PRISM 7.0a . A Kolmogorov–Smirnov test was applied to evaluated variable distribution. Non-normally distributed variables  were expressed as medians (interquartile range) and analyzed by Kruskal–Wallis’ test. Normally distributed variables (age) were expressed as mean ± standard deviation (SD) and analyzed by 1-way ANOVA test with Bonferroni’s correction for multiple comparisons. Categorical variables (sex) were expressed as absolute number and percentage (%) and analyzed by χ² (when applicable) or Fisher’s tests. Matched measurements (plasma vs. CSF), variables were analyzed by Wilcoxon pairs signed rank test.Supervised learning algorithms were used to combine levels of expression of single EV surface markers in a specific EV surface marker signature and discriminate patients according to clinical diagnosis. Linear discriminant analysis was used as a feature reduction strategy to build the 3D canonical plots ; canonical components were calculated from the weighted linear combination of expression levels for the 37 EV markers in order to maximize the separation between the 4 groups ; each point represents a patient and spheres include patients with a linear combination coefficient that falls within the mean of canonical components 1, 2, and 3 ± SD. The diagnostic models were built exploiting a random forest (RF) classification algorithm, as previously reported ,22,23. BThe basic RF models were built on the expression of 17 EV surface markers , which were demonstrated to be differentially expressed in plasma samples in HC, PD, MSA, and AP-Tau in our previous study [The integrated version of RF models  was built selecting only markers expressed in CSF- and plasma-derived EVs from patients with PD , MSA , or AP-Tau . Integrated models were directly validated on the original discovery cohort. A representative classification tree was shown for each model, and a confusion matrix reported accuracy, sensitivity, specificity, positive and negative predictive values.p > 0.05 for all comparisons). The plasma discovery cohort included 84 patients from our previous study [The optimization cohort included 16 patients: 4 PD, 4 MSA, 4 AP-Tau , and 4 healthy controls (HC). These subjects underwent plasma and CSF collection for paired flow cytometry analysis. Clinical characteristics are summarized in us study  and was p = 0.048); this difference was mainly due to larger vesicles  revealed higher concentration of CSF-derived nanoparticles/mL in PD compared to HC . Plasma samples showed higher numbers of nanoparticles/mL compared to CSF, even after stratification for EV diameter , compared to CSF (p = 0.005). Among the 37 EV surface markers analyzed in paired plasma vs. CSF samples, 5 markers were differentially expressed in the PD group, 11 in MSA, and 8 in AP-Tau. All these markers were more highly expressed in plasma than CSF except for CD9 in the MSA group . A random forest (RF) model (we will refer to this model as “basic” throughout the present manuscript) was built combining levels of expression of these EV markers . Among tn = 84; The level 1 RF basic model  , generated via outward budding of the plasma membrane, rather than exosomes (40–120 nm) produced in multivesicular bodies via endosomal pathway . Indeed,Regarding the EV immune profiling by MACSPlex human exosome assay applied to CSF-derived EVs, no statistically significant differences were observed in the 37 surface markers between groups. This is certainly due to the main limitation of this explorative study which is the low number of subjects analyzed in each diagnostic category. However, the simultaneous quantification of multiple EV markers increased the power of the assay and displayed different EV profiles of expression in subjects with PD and AP vs. HC, which allowed a good discrimination of patients in accordance with the clinical diagnosis by linear discriminant analysis. Of interest, PD and AP patients expressed higher amounts of HLA-I, CD8, CD2, CD3, CD14 and CD20 in CSF, while no or very low detection was observed in HC, suggesting a CNS activation of the immune system, in particular of the T cell-mediated immunity with particular emphasis on intracellular endogenous synthetized antigens that involves the activation of HLA class I  and are CD105 is highly expressed in CSF of PD and MSA. Even if it is used as an endothelial cell marker during angiogenesis , it was Finally, levodopa represents the first-line therapy in PD. Several drugs may influence the mechanism of biogenesis and release of EVs ; howeverThis is an explorative study and the low number of subjects in the CSF cohort is certainly a limitation; therefore, larger studies and validation in external cohorts of patients are warranted. In addition, it is an antemortem study, lacking the diagnostic confirmation of brain histopathologic analysis. Finally, although it is beyond the primary scope of this paper, a deeper characterization of CSF-derived EVs with different techniques such as transmission electron microscopy (TEM), would be insightful. However, the enrichment of vesicle fraction by immunocapturing displays an inherent limitation for TEM analysis; in fact, a bead–EV complex might impair the ultrastructural morphological characterization of nanosized vesicles. Nevertheless, we can speculate that at least for plasma-derived EVs, by avoiding ultracentrifugation, which is known to lead to EV deformation and rapture into smaller particles , the morIn conclusion, a diagnostic model based on plasmatic EVs, built via machine learning, integrating information provided by the simultaneous profiling of CSF and plasma could potentially impact on clinical practice. Furthermore, the EV surface markers characterization bolsters the concept of a relevant involvement of inflammation in PD and it underscores the importance of EVs as pathways/biomarkers for protein aggregation-related neurodegenerative diseases.


To reduce patient and procedure identification errors by human interactions in radiotherapy delivery and surgery, a Biometric Automated Patient and Procedure Identification System (BAPPIS) was developed. BAPPIS is a patient identification and treatment procedure verification system using fingerprints.etc. To identify a patient, the BAPPIS reads a fingerprint, identifies the patient, verifies with a second fingerprint to confirm when multiple patients have same fingerprint features, and connects to the patient’s record in electronic medical record (EMR) systems. To validate the system, 143 and 21 patients ranging from 36 to 98 years of ages were recruited from radiotherapy and breast surgery, respectively. The registration process for surgery patients includes an additional module, which has a 3D patient model. A surgeon could mark ‘O’ on the model and save a snap shot of patient in the preparation room. In the surgery room, a webcam displayed the patient’s real-time image next to the 3D model. This may prevent a possible surgical mistake.The system was developed using C++, the Microsoft Foundation Class Library, the Oracle database system, and a fingerprint scanner. To register a patient, the BAPPIS system requires three steps: capturing a photograph using a web camera for photo identification, taking at least two fingerprints, and recording other specific patient information including name, date of birth, allergies, nd fingerprints from 143 patients as the system designed. A false positive recognition was not reported. The 96.9% completion ratio is because the operator did not verify with another fingerprint after identifying the first fingerprint. The reason may be due to lack of training at the beginning of the study.1,271 (96.9%) of 1,311 fingerprints were verified by BAPPIS using patients’ 2We successfully demonstrated the use of BAPPIS to correctly identify and recall patient’s record in EMR. BAPPIS may significantly reduce errors by limiting the number of non-automated steps. Patient identification and procedure verification are well-known problems in the medical industry. The number of serious or even fatal consequences is growing. Accreditation by the Joint Commission demands accuracy of patient identification by using at least two patient identifiers .Unfortunately, the most popular identifier, wristbands, is proving to have an unacceptable error rate. These misidentifications can lead to a medical misadministration and falls under the category of a ‘sentinel event’. A ‘sentinel event’ is defined by the Joint Commission as “an unexpected occurrence involving death or serious physical or psychological injury, or the risk thereof ” . The senThe Joint Commission analyzed the causes of misadministration in 2005 as illustrated in The ‘two patient identifiers’ specified by the Joint Commission have a two-fold purpose: firstly, to reliably identify the individual and secondly, to match the service or treatment to that individual. The identifiers may be in the same location, such as a wristband. They must be directly associated with the individual, and the same two identifiers must be directly associated with the treatments or procedure. The ‘two-identifier’ requirement also applies to an ‘order for care’ and to report critical test results. Wristband systems are the most common patient identifier in use. These identifiers play an important role in the Joint Commission protocol to reduce surgical misadministration.Effective July 1, 2004, compliance with the Universal Protocol for Preventing Wrong Site, Wrong Procedure, Wrong Person Surgery has been required of all Joint Commission accredited organizations, to the extent that these requirements are relevant to the services provided by the organization . An impoThere are a few competing technologies for patient identification, namely barcode and radio frequency identification (RFID) chips. RFID can be used to track the patient’s location and extract patient information using a remote scanner –8. HowevBarcode or RFID chips can be taped on patient wristbands. However, their effectiveness of identifying patients is not convincing. There are two critical studies of the barcoded wristbands, which have a significant pool. The first study was reported by the State University of New York, Downstate Medical Center in Brooklyn, New York . The wriDuring the two years, wristbands were examined 1,757,730 times, and 45,197 wristband errors were found. The mean wristband error rate for the first quarter was 7.4%. However, by the eighth quarter, the mean wristband error rate had fallen to 3.05%. Even with this improvement, sentinel events continued to rise as shown in A second study was conducted at the Veterans Affairs Medical Center in West Los Angeles, California, and compared wristband identification errors for 712 hospitals. Phlebotomists checked 2,463,727 patients’ wristbands, finding 67,289 errors .Ten percent of these hospitals had error rates of 10.9% greater. Patients’ wristbands were missing in 33,308 cases, representing 49.5% of errors. Multiple wristbands with different information occurred 8.3% of the time; wristbands with incomplete data 7.5%; erroneous data 8.6%; illegible data 5.7%; and patients wearing wristbands with another patient’s identifying information occurred 0.5% of the time.We developed a biometric system using fingerprints to meet the Joint Commission’s recommendations and minimize error rates. Our system was designed to interact with Radiology Information System (RIS) and EMR and can potentially eliminate most of the problems associated with wristband systems while helping clinics meet the goals set by the Joint Commission. Patient misidentification is limited to the failure rate of fingerprint identification, which is approximately one out of a billion (provided the patient can offer two fingerprints). Also, procedure verification can be performed biometrically by interacting with the relevant patient database such as an electronic chart or RIS system. Moreover, fingerprints are not subject to loss, damage, or switching between patients in the same way as plastic wristbands. Multiple records for one patient can be prevented since there is one set of unique biometric information , 13. AlsThe project team included a Human Factors Analysis expert to insure the total system (hardware and humans) functions, not just the technical aspects. System design has recently begun to focus on human factors’ considerations. According to Kukula et al. , The HumThe successful deployment of biometric systems, regardless of application, needs to take into consideration how individuals interact with the device. Failure to do so will cause a degradation of the optimal performance of the biometric sensor, causing problems such as failure to acquire, failure to enroll, and impacts on the false rejection rate. Moreover, if the individual cannot successfully interact with the biometric device, there is a potential for a failure to function even when the device is implemented.e.g. the patient), the other equally important person in the interaction is the user, the person using the fingerprint biometric device to identify the patient. In fact, the success or failure of the biometric device usually depends on the performance of the user who will provide instructions to the patient and guide the patient through correct finger orientation, force application, and placement in order to acquire a fingerprint sample of sufficient quality for reliable identification. Rood and Jain  cables as illustrated in The hardware consists of personal computers, a database server, optical fingerprint scanners, and web cameras. They are connected The model of the optical fingerprint scanner is SFR300-S (Suprema Inc.). It has a 500 dpi/256 Gy scale optical fingerprint sensor in a plastic case. The scan window is 16 mm × 18 mm. Its physical dimension is 40 mm (width) × 77 mm (length) × 70.5 mm (height). Scanning time takes less than a second. The web camera used is an inexpensive CS431 by Intel.® Visual C++. Each patient’s record in the fingerprint database consists of three components: fingerprint images, a photo image, and a text record. Each scanned fingerprint has key information extracted and stored in a proprietary format  (Our program is written in Microsoftryption) . The phoFingerprint recognition is handled through the UniFinger Engine, a proprietary algorithm provided with the scanner. When we use fingerprint recognition engines, we need to take into account two possible errors. The first one is the false match (FM), and the second one is the false non-match (FNM). The FM refers to the mismatching fingerprints. The FNM is the inability to match a fingerprint to one in the database. These two errors can be adjusted as variables in our system. If the FM rate is set low because false match is a serious security problem, then the fingerprint recognition engine rejects even the tiny mismatch. As a result, the rate of false non-match (rejection) increases. This will translate into more frequent rejections and retries. According to the result of the international fingerprint verification competition in 2006 (FVC2006), the fingerprint recognition algorithm that we are using resulted in a 1.36% FNM rate when FM rate was set to 0%, and a 0.79% FNM rate when the FM rate was set to 0.1%  .We employed two-fingerprint identification step with two different fingers in our system. We set FM rate to 0.1% for the first fingerprint identification to avoid FNM. Then, for the second fingerprint, we verify the identification result by setting FM rate to 0.000001%, so that we can prevent the false positive identification. With two fingerprints, the identification error probability is one out of 100 billion. In single fingerprint mode (using one fingerprint), the error probability is one in 100,000.We also utilize a quality index of the initial fingerprint registration. UniFinger engine provided the fingerprint image quality index in a percentile scale. A good quality fingerprint has distinguishable patterns and features that allow the extraction of features that are useful for subsequent matching of fingerprint pairs. The fingerprint image quality index is a predictor of a pattern recognition algorithm’s performance , and it Our scanner system connects to the fingerprint database using an open-database connectivity (ODBC) driver. ODBC provides a standard method for using database management systems (DBMS). ODBC is designed to be independent of programming languages, database systems, and operating systems . ODBC mae.g., importing a picture to the wrong patient).We felt it was important to make the initial record creation of a patient’s one seamless operation run by a single program. To create a new record, the text information is entered and the patient was photographed with a web camera as displayed in After scanning one finger, the system identifies a patient , and the patient photograph is displayed. Scanning only one finger is an option. A second finger is then scanned to confirm identification. The photograph display is an additional visual check for the patient and staff.We designed the software to interact with other hospital databases using a modular approach. The current module interacts with the radiation oncology Mosaiq , RIS (PACS), and EMR database as shown in etc. A combined fingerprint database was created from both departments, one database from each department. This was designed to prevent duplicate files for a patient.Our project included two departments to test our prototype. For the testing of our prototype system and full clinical study, we acquired an Institutional Review Board (IRB) protocol (CC862) approval. A timing routine was programmed into the software to track the amount of time the user interacted with the software as one measure of functionality and usability. The measurements were saved in log files. The measurements included user logins, fingerprint recognition failures, process durations, All operations with patient information were automatically recorded on encrypted database log files. The files were reviewed once a week by the Principal Investigator. For physical security, the computer database was protected in a locked data server room, while the clinical computers were subject to hospital security measures.For radiation therapy, our system was set up at a receptionist desk and treatment machine console areas to perform two basic tasks: 1) The identification of a patient and entering them into the treatment queue; and 2) The identification of a patient being prepared for treatment and the loading of their treatment settings to the machine. At the receptionist desk, the hardware includes a webcam with a resolution of 640 × 480, a personal computer, and an optical fingerprint scanner. A receptionist enrolled new patients through the process. When patients returned to the clinic for daily scheduled treatments, they were asked to scan one/two fingers depending on whether the single or two-fingerprint identification mode was being used on the scanner at the reception desk. Our program identified these patients and added them to the waiting list maintained in the Mosaiq system. This process allowed the therapists at the treatment machine to know that the patient had arrived for treatment.When a patient walked into the treatment room, he/she was asked to scan his/her fingers. The photo window was displayed for the therapist to use for visual confirmation of the patient as a second identification after the patient’s fingerprint match. Next, our system retrieved the patient treatment machine settings in the Mosaiq system for their radiotherapy.At each patient visit, after fingerprint(s) were scanned, the system identified and displayed the patient’s photo. It provided the connection to other hospital databases, such as Mosaiq, RIS, and electronic medical record.We installed the BAPPIS system in the UH Cleveland Medical Center Surgery Department where an average of 40 breast surgeries per month are performed in 30 surgical suites. Our systems were installed in two breast consultation suites, one surgery preparation room, one surgery reception desk, and two consultation rooms. Our software provided a module for the surgery department, which allowed a surgeon to create a procedure/orientation verification display consisting of an anatomical sketch, procedure description, and digital image of the patient in treatment position. Once a patient information was recorded in the system, his/her surgeon could create a short surgery description and added an anatomical sketch appropriate to the surgical site from a library, which was available from our software. Most of the information was entered by the surgeon in the consultation room, allowing them to discuss the procedures with the patient. The surgeon clearly marked “yes” on the sketch following the Joint Commission recommendation  for markAt the time of surgery, as the patient entered the surgical suite, his/her fingers were scanned and identified. Once the patient was placed on the surgical couch, a photo was taken and displayed next to the anatomy sketch as illustrated in Once the surgery was completed, the patient file including notes and digital image after surgery was exported to an electronic patient chart and saved in our software system. This eliminated possible confusion during future additional surgeries.A module was designed for adding an authorized user along with their fingerprint to the database. There was a range of privileges that could be assigned to the user based on security requirements and the users’ function. Only privileged users were able to open a patient’s history and modify the patient’s information.We created two clinical fingerprint databases, one for the radiation oncology department and one for the surgery department. The two clinical databases were combined and stored in a node server. This multi-database system could be scaled up to model an entire hospital with multiple satellite clinics.The multi-database architecture used asymmetric cryptography for safe data transfer when communicating between databases. A pair of keys was used to encrypt and decrypt a message and signature so that it was transmitted securely. The communication between fingerprint database servers was therefore confidential and secure, as required by HIPAA , 23. OurAsymmetric cryptography can be illustrated by an example where ‘John’ wanted to send a fingerprint to ‘Susie’ securely. A fingerprint was sent to Susie (the remote server) encrypted using Susie’s public-key, and John’s signature (credibility) was included, but encrypted with John’s private-key. John could get Susie’s public key from a public administrator. When Susie got the fingerprint, she decrypted it with her private key, to which no one else should have access. However, she had to verify that it was John who sent the package. John sent his signature encrypted with his private key to Susie who used John’s public key to decrypt his signature. This asymmetric cryptography had been used for internet banking .via network as it dictates the header information to be used for standardized communication when transmitting biometric information (like fingerprints).We also implemented the Common Biometric Exchange Formats Foundation (CBEFF) proposed by the National Institute of Standards and Technology (NIST) . CBEFF wBAPPIS identified 1,311 fingerprints from 143 patients prior to treatment as a graph created in We successfully demonstrated the use of BAPPIS to correctly identify and recall patient plan information using fingerprint identification. BAPPIS could help significantly reduce the number of errors by limiting the number of non-automated steps in the treatment delivery process. The cost of this system is very minimal. A fingerprint scanner’s cost was less than $100, and data server was about $5,000.A significant effort was made toward developing a user-friendly interface . And emphasis was placed on creating a system that patients and professionals could easily use with minimal training. We performed a human factor analysis in every interface during an identification and minimized challenges to the successful operation of the device, such as when handling patients with cognitive or attention limitations, frail elderly patients with loose skin in the fingertips, and patients with vision, hearing, and language difficulties. Every attempt was made to include persons having these characteristics. The inclusion of these patients as test subjects was not subjected to sampling restrictions associated with statistical predictive validity since the total number of subjects was restricted for practical purposes, and the impetus for the testing was not to predict levels of performance in the general population, but rather to identify and eliminate performance problems associated with the device.We opened an IRB protocol and received all participated patients’ consents. We followed HIPAA regulations and recommendations for medical information protection. Our system only stored the identification information  with data encryption. Firewall software was installed on the database server, and security patches were monitored and installed. The patient database only exists within the secure hospital intranet and was never exposed to the internet. Communication between hospitals was through virtual private networks (VPNs). There were few patients who had concerns about taking fingerprints and did not enroll.The comparison between current identification and the use of BAPPIS will be done in the future. Since clinical studies with an IRB required the use of the current identification method by asking name and birthday in addition to BAPPIS, the error rates between two methods were not analyzed.Since we initiated our study, many other biometric systems have been introduced such as fingerprint and vein scanners, palm scanners, and face recognition systems.We successfully demonstrated the use of BAPPIS to correctly identify and recall patient’s record in EMR. BAPPIS may significantly reduce errors by limiting the number of non-automated steps.The original contributions presented in the study are included in the article/supplementary materials; further inquiries can be directed to the corresponding authors.The studies involving human participants were reviewed and approved by Case Western Reserve University and University hospital IRB. The patients/participants provided their written informed consent to participate in this study.JS took charge in the PI and writing of the manuscript. HK and SP developed the system as Co-Inv and wrote the manuscript. SL contributed to the writing of the manuscript. JM and TM were in charge of Co-Inv and writing of the manuscript. TK, MY, CK, SL, RS, and MM participated in the research and writing of the manuscript. All authors contributed to the article and approved the submitted version.The project in this manuscript was supported by an AHRQ 5R18HS017424 GRANT. For this clinical study, an IRB was approved by the University Hospitals of Cleveland and Case Western Reserve University School of Medicine. Case Comprehensive Cancer Center; 5P30CA043703.SP was employed by Cure-In Incorporated. TM was employed by Carlow International Incorporated.The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


The potential scarring effects of long-term youth unemployment and social disengagement have for many years challenged policymakers to develop successful and sustainable interventions.


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The Editorial Office has been made aware of potential issues surrounding the scientific validity of this paper, hence has issued an expression of concern to notify readers whilst the Editorial Office investigates.


This manuscript has been updated in order to amended incorrect affiliation indices for several authors. The publisher apologies for any confusion caused.


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The Editorial Office has been made aware of potential issues surrounding the scientific validity of this paper, hence has issued an expression of concern to notify readers whilst the Editorial Office investigates.


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The Clark Tibbitts Award lecture will feature an address by the 2020 award recipient, Jan Abusharkrah, PhD, FAGHE. AGHE’s Clark Tibbitts Award was established in 1980 and named for an architect of the field of gerontological education. The award is given each year to an individual or organization that has made an outstanding contribution to the advancement of gerontology and geriatrics education.


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The Editor has retracted this article  because Authors Chuncheng Zhang, Jing Yue, Mingyue Li, Wei Jiang, Yu Pan, Zhimin Song, Cailian Shi, Weixuan Fan and Zhenxiang Pan all agree to this retraction.


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In this paper, we present MachSMT, an algorithm selection tool for Satisfiability Modulo Theories (SMT) solvers. MachSMT supports the entirety of the SMT-LIB language. It employs machine learning (ML) methods to construct both empirical hardness models (EHMs) and pairwise ranking comparators (PWCs) over state-of-the-art SMT solvers. Given an SMT formula


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The Irving S. Wright Award of Distinction Lecture will feature an address by the 2020 recipient James L. Kirkland, MD, PhD. This award is given by the American Federation for Aging Research, Inc.


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NUT癌是以染色体15q14上睾丸核蛋白（nuclear protein in testis, NUTM1）重排为特征的一种罕见的恶性程度极高的肿瘤，其发病机制及治疗方法目前尚不明确，其预后极差。因其好发部位主要集中在躯体中线位置，如眼眶、鼻腔、上颚、纵隔等，故又称为中线癌。四川大学华西医院胸部肿瘤科收治了1例肺NUT癌患者，为70岁老年男性，初诊为体检发现左肺门占位，术后病理提示低分化癌，经荧光标记的原位杂交技术证实为NUT癌，术后经化疗、抗血管治疗、放疗等综合治疗获得了较长的生存期。本文结合文献回顾报告了肺NUT癌这一少见实体瘤的临床、病理特征及治疗策略。


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Europe has a window of opportunity to embark on a recovery that tilts towards digitalisation and a greener economy, and stands to generate sustainable benefits for its people.


Early assessment of diffusion and possible expansion of SARS-CoV-2 Lineage 20I/501Y.V1  in France, January to March 2021’ by Gaymard et al., published on 4 March 2021, a recognition of the laboratories belonging to the ColVHB network was added to the Acknowledgements section. This change was made on request of the authors on 5 March 2021.In the article ‘


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We provide graded extensions of algebraic theories and Lawvere theories that correspond to graded monads. We prove that graded algebraic theories, graded Lawvere theories, and finitary graded monads are equivalent via equivalence of categories, which extends the equivalence for monads. We also give sums and tensor products of graded algebraic theories to combine computational effects as an example of importing techniques based on algebraic theories to graded monads.


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Sooner or later, the ECB must accept that monetary financing in support of deficit spending is a necessity not just for mitigating the coronavirus crisis, but also for averting a downward deflationary cycle that could pull the eurozone apart.


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This article originally contained the following statement in reference to ZELNORM (tegaserod): "It is not prescribed in the USA."However, on August 15, 2019, ZELNORM (tegaserod) was reintroduced to the United States market. Therefore, the text has been amended to reflect that ZELNORM (tegaserod) is indeed currently prescribed in the USA. The authors and Cureus sincerely regret the error.


The Editorial Office has been made aware of potential issues surrounding the scientific validity of this paper, hence has issued an expression of concern to notify readers whilst the Editorial Office investigates.


The Donald P. Kent Award lecture will feature an address by the 2019 Kent Award recipient, Terry Fulmer, PhD, of The John A. Hartford Foundation. The Kent Award is given annually to a member of The Gerontological Society of America who best exemplifies the highest standards of professional leadership in gerontology through teaching, service, and interpretation of gerontology to the larger society. The Robert W. Kleemeier Award lecture will feature an address by the 2019 Kleemeier Award recipient, Steven Zarit of Pennsylvania State University. The Kleemeier Award is given annually to a member of The Gerontological Society of America in recognition for outstanding research in the field of gerontology


The fifth author, T. N. C. Ramya, was incorrectly attributed equal contribution to this work with Kamaldeep Kaur, Indu Khatri, and Akil Akhtar. Only the first three authors, Kamaldeep Kaur, Indu Khatri, and Akil Akhtar, should be noted as contributing equally to this work. The publisher apologizes for the error.


Epidemiology & Infection with the indication that A. Pichón Riviere's surname should be indexed as ‘Riviere, AP’ instead of ‘Pichón Riviere, A.’ and was originally published as such.The above paper was originally submitted to This has been rectified in the online PDF and HTML copies and re-indexed accordingly.


The authors wish to make the following erratum in this paper .Research Center for Eco-Environment Sciences, Chinese Academy of Sciences, Beijing 100085, China; ljbao_st@rcees.ac.cn (L.B.); dretfr456@gmail.com (W.C.); chenhao@rcees.ac.cn (H.C.); yswei@rcees.ac.cn (Y.W.)College of Resources and Environment, University of Chinese Academy of Science, Beijing, 100049, ChinaThere are mistakes in the spelling of the first and second institute names of the authors:Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China; ljbao_st@rcees.ac.cn (L.B.); dretfr456@gmail.com (W.C.); chenhao@rcees.ac.cn (H.C.); yswei@rcees.ac.cn (Y.W.)College of Resources and Environment, University of Chinese Academy of Sciences, Beijing, 100049, ChinaThe corrected spelling should be:The authors apologize for any inconvenience this may have caused.


In the Funding statement, the RSP number from the funder Researchers Supporting Project, King Saud University, Riyadh, Saudi Arabia is listed incorrectly. The correct RSP number is: RSP-2020/194.


EML4-ALK)融合占非小细胞肺癌患者的3%-5%。随着对该驱动基因的深入研究，以Crizotinib为代表的ALK抑制剂逐渐被开发并应用于临床。然而，不同患者对ALK靶向治疗的反应存在差异，且多数ALK靶向治疗患者最终会不可避免地出现耐药，导致肿瘤进展。利用预后标志物监测患者疗效及时改变治疗方案，以及根据耐药机制选择个体化的后续治疗，可以有效地改善患者的预后。本文将对ALK抑制剂的耐药机制以及相关的预后标志物展开综述，探讨ALK靶向治疗疗效预测以及耐药患者后续治疗方案的选择。棘皮动物微管相关类蛋白4-间变性淋巴瘤激酶(echinoderm microtubule-associated protein like 4-anaplastic lymphoma kinase,


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Social distancing restrictions, as measured by the Oxford stringency indicator, constitute the one variable that is most tightly correlated with the recession and recovery across EU member states.


It has the traditional advantage that algorithms for branching bisimilarity are more efficient than ones for other weak behavioural equivalences, especially weak bisimilarity. With lgorithm , resulti


CDO1作为抑癌基因常在肿瘤发生早期便会发生甲基化改变, 因此本研究旨在探讨CDO1甲基化在肺癌早期诊断中的价值。肺癌的发生率和死亡率常居所有恶性肿瘤的首位, DNA甲基化作为表观遗传学之一参与肿瘤的发生发展过程, 收集肿瘤患者和健康人群的外周血液样本, 游离DNA通过亚硫酸盐修饰并结合实时荧光定量PCR检测CDO1在外周血中的甲基化水平。CDO1的甲基化水平在性别、淋巴结转移和肿瘤原发灶-淋巴结-转移分期的分层比较中存在显著性差异(P < 0.05)。CDO1对肺癌诊断的灵敏度和特异性分别为52.2%和78.6%。其诊断的整体准确度明显高于应用于临床的肿瘤标志物而且对I期、II期患者的诊断灵敏度表现最好。此外, CDO1可有效增加多项联检中诊断的灵敏性。肺癌患者的外周血的基因甲基化水平明显高于肺部良性疾病患者及健康人群。肺癌患者CDO1的甲基化水平对肺癌的早期诊断具有潜在的巨大优势。检测


Acta Cryst. (2020), E76, 742–746.Corrigendum to  Acta Cryst. (2020), E76, 742–746], there is an error in the chemical names of the title compounds.In the paper by Sugiyama [ Abstract are correct.The chemical names of the title compounds in the paper by Sugiyama 2012 are inco


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The authors of “Towards a cancer mission in Horizon Europe: recommendations” : 1589‐1615. PMID: 32749074) [


On 2 April 2020, the European Commission (2020) duly put forward a proposal for the creation of a European instrument for temporary Support to mitigate Unemployment Risks in an Emergency (SURE). This bold and innovative move must be welcome, but the actual profile of this new instrument requires clarification to avoid misunderstandings, false expectations and eventual disappointment.


The Editorial Office has been made aware of potential issues surrounding the scientific validity of this paper, hence has issued an expression of concern to notify readers whilst the Editorial Office investigates.


It has been brought to our attention that the methods and results presented in  are almoSensors.MDPI is a member of the Committee on Publication Ethics and takes seriously its responsibility to publish only high-quality research. We regret that this was not discovered prior to publication and offer our apologies to the readers of


Keynote at the 20th European Conference on Eye Movement Research (ECEM) in Alicante, 22.8.2019Video stream:https://vimeo.com/361729502


In Figs


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The authors regret that original paper was published with errors in Table 2. The number of men have been switched. Correct values areMenNonobese n = 163,Obese n = 89.The authors apologies for any inconvenience caused.


The Joseph T. Freeman Award lecture will feature an address by the2020 Freeman Award recipient Cynthia Brown, MD, MSPH. The Joseph T. Freeman Award is a lectureship in geriatrics awarded to a prominent physician in the field of aging, both in research and practice. The award was established in1977 through a bequest from a patient’s estate as a tribute to Dr. Joseph T. Freeman.


The COVID-19 pandemic carries heavy threats, and preserving stable and coordinated international trade relations will be essential to avoid catastrophic disorders or conflicts.


Although austerity was particularly strong in the aftermath of the economic crisis of 2008 and its consequences in the euro area, Italian fiscal policies have been characterised by tough consolidation periods ever since the 1990s.


We extend the


Due to a technical error with the Cureus software, all instances of P-values measuring "< .0001" were erroneously omitted from Tables 1-3. These p-values have been restored to the tables. Cureus sincerely regrets the technical and editorial errors that led to this article being published without the p-values.


There is an error in the footnote of


Keynote by Enkelejda Kasneci at the 20th European Conference on Eye Movement Research (ECEM) in Alicante, 18.8.2019,Video stream of presentation: https://vimeo.com/356314274


It was highlighted that the original article  containeIncorrectThe returned similarity score is based on Jaccard similarity [18] of Morgan-style connectivity fingerprints [19] with a radius of up to 5.CorrectThe returned similarity score is based on Jaccard similarity [18] of Morgan-style connectivity fingerprints [19] with a radius of up to 3.


Therefore, we’d like to declare a correction to the authorship that Prof. Ma is listed as one of the corresponding authors.


The revised version of


An investigation was conducted in accordance with Frontiers guidelines and the authors failed to provide a satisfactory explanation.This retraction was approved by the Chief Editors of Frontiers in Oncology and the Editor-in-Chief of Frontiers. The authors agree to this retraction.


Supplement 1 published in Volume 20 of BMC Plant Biology contained several incorrect 'received dates'


Medicine has published two,2 articles with protocol mistakenly added to the title. The titles have been updated to remove this.In recent issues,


A toolkit of tagged glp-1 alleles reveals strong glp-1 expression in the germline, embryo, and spermatheca. microPublication Biology. The authors correct the following:JK5525 glp-1(q46) III; qSi155[Cbr-unc-119 + glp-1::Halotag] IV’is corrected to‘JK5225 glp-1(q46) III; qSi155[Cbr-unc-119 + glp-1::Halotag] IV’In the Methods section:The strain‘JK5526 glp-1(q46) III; qSi156[Cbr-unc-119 + glp-1::Halotag] IV’is corrected to‘JK5226 glp-1(q46) III; qSi156[Cbr-unc-119 + glp-1::Halotag] IV’The strain‘Throughout the text and in the Methods section:3xOLLAS]”is corrected to:“[glp-1::2xOLLAS]”The genotype of strain JK5973“[glp-1::


It has been brought to our attention that this paper  was susp


The Editorial Office has been made aware of potential issues surrounding the scientific validity of this paper, hence has issued an expression of concern to notify readers whilst the Editorial Office investigates.


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In our paper


The affiliations for the first author are incorrect. Minlu Li is not affiliated with both #1 and #2, but #1 only: General Ward of Neurology, West China Hospital/ West China School of Nursing, Sichuan University, Chengdu, Sichuan, China.


The authors regret that the funding information given in the original manuscript was incorrectly shown. The authors declare that there was no financial support for this research.The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers.


With distinct levels of completeness and capabilities to model different developmental stages, embryo models offer an experimental platform for To view this SnapShot, open or download the PDF.


The online version of the “Clinico-radiological Observations in Meconium Aspiration Syndrome”:510–5) has been updated according to the letter to the editor and respective authors' reply published in JNMA 213 Issue.


In


The authors would like to make the following corrections to the published paper .Replacing the Institutional Review Board number 2019800990B0 with 201800990B0.


The authors should be congratulated on reporting their findings in a large radical cystectomy cohort for muscle-invasive (MIBC) and metastatic bladder cancer . The man


Sci., 2021, DOI: 10.1039/d1sc00001b.Correction for ‘Mechanochemical generation of acid-degradable poly(enol ether)s’ by Jinghui Yang  The authors regret an error in The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers.


TED’ by Yuka Kobayashi et al., Chem. Sci., 2020, DOI: 10.1039/d0sc03521a.Correction for ‘Crystal structure and metallization mechanism of the π-radical metal  The authors regret an error in The correction of The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers.


There is an error in the affiliation for authors Stephane Perrey and Makii Muthalib. The correct affiliation is: EuroMov Digital Health in Motion, Univ Montpellier, IMT Mines Ales, Montpellier, France.


The corrected list of affiliations is as shown here.The authors regret that the one of the affiliations (affiliation The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers.


The journal is issuing this expression of concern to alert readers to significant concerns regarding the paper cited above .Serious concerns have been raised about misinterpretation of the data and the conclusions.The major concern is the misrepresentation of the COVID-19 vaccination efforts and misrepresentation of the data, e.g., Abstract: “For three deaths prevented by vaccination we have to accept two inflicted by vaccination”. Stating that these deaths linked to vaccination efforts is incorrect and distorted.We will provide an update following the conclusion of our investigation. The authors have been notified about this Expression of Concern.


The hazard ratio label on the first line of


In the original publication  there waNone.Taishan Scholars Program of Shandong Province (NO.ts 20190982).


The authors of  would li


Italy’s economy is not expected to return to pre-pandemic levels before the first half of 2023, and an early return to budgetary constraints would be disastrous.


Following the publication of the original article , we wereCorrected units are represents in Bold:Table 2109/L)WBC (1012/L)RBC (HGB (g/L)HCT (L/L)MCV (fL)MCHC (g/L)RDW (%)109/L)PLT (109/L)Neutrophils (109/L)Lymphocytes (109/L)Monocytes (109/L)Eosinophils (109/L)Basophils (Table 3(nmol/L)Total T4


Furthermore, they regret that these errors were introduced into the paper, even though they did not substantially alter any of the major conclusions reported in the paper, and apologize to the readership for any inconvenience caused.The corrected versions of


Page 1, line 23: “>3 kb” should read “<3 kb.”Volume 10, no. 39, e00715-21, 2021,


The first sentence, “The United Nations Humanitarian Commission for Refugees (UNHCR)” should say “United Nations High Commissioner for Refugees (UNCHR)”.In the original publication,The author apologises for this error.


Hortae werneckii, which occurs mainly in tropical and subtropical regionsTinea nigra is a rare, chronic, asymptomatic, and superficial keratophytosis caused by the dematiaceous fungus


There is an error in


In


The authors regret errors in Fig. Fig. 2 TEM (a) and HRTEM (b) images of FMSPs. d Magnetic curve of FMSPs. g PL emission and excitation spectra of FMSPs


After having been in contact with the authors, they agreed with the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused.


Bioscience Reports at the request of the authors following receipt of a notification from a reader, alerting the Editorial Office to the data in Figures 5A and 5C as well as the Western blots in Figures 1C and 6B.This article is being retracted from The Editorial Office contacted the authors to request the raw data and raw images of the Western blots, to which the authors responded with the Retraction request stating that the integrity of the research was damaged. Given the concerns raised the Editor-in-Chief and Editorial Board agree with the Retraction. The co-corresponding author Huang-Shan wishes to take full responsibility for their negligence, and apologizes for the inconvenience caused to the journal and readers.


In the original publication, the authors contributing equally to this paper was not presented clear.The corrected text is given below:Jian-Jun Zhao and Song-Yu Li have contributed equally to this work.


In Tables


CLINICS (Sao Paulo). 2021;76:e2914errhttps://doi.org/10.6061/clinics/2021/e2914, published in 2021.Erratum for: doi: Expression of Amphiregulin in Enchondromas and Central Chondrosarcomas, RESULTS section in the Abstract, remove the following sentences:In the article “Enchondromas or chondrosarcomas? Please clarify. This will help understand the next sentence on enchondromas localized in short bones and long bones.”


To the editor,We appreciate very much your comment about our paper published recently in Int Braz J Urol . In respThe Authors


The Editorial Office has been made aware of potential issues surrounding the scientific validity of this paper, hence has issued an expression of concern to notify readers whilst the Editorial Office investigates.


The Editorial Office has been made aware of potential issues surrounding the scientificvalidity of this paper, hence has issued an expression of concern to notify readerswhilst the Editorial Office investigates.


In our paper


The correct affiliations are listed in this correction notice.The authors regret that affiliation The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers.


Sci., 2019, 10, 10524–10530, DOI: 10.1039/C9SC03829A.Correction for ‘A hybrid blue perovskite@metal–organic gel (MOG) nanocomposite: simultaneous improvement of luminescence and stability’ by Samraj Mollick  The formula should read EA2PbBr4.The authors regret that the formula used for the 2D perovskite EAPbBrThe Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers.


There is an error in the caption of


Erratum zu:Bundesgesundheitsbl 202110.1007/s00103-021-03396-9In der ursprünglichen Originalfassung des Artikels wurden einige Namen der Autorinnen und Autoren nicht korrekt wiedergegeben.Die Namen wurden nun korrigiert.


In this paper, the phrases should be corrected as follows:4. Desmoceras (D.) japonicum Yabe.1)”For “4. Desmoceras (P.) japonicum Yabe.1)”.read “5. Desmoceras ezoanum Matsumoto.”For “5. Desmoceras (P.) ezoanum Matsumoto.”.read “


In the original publication, the section “Acknowledgments” is not be included. The Acknowledgments section is given in in this correction.Acknowledgments This research was partly supported by AMED under Grant Number JP18ck0106463.


Across the board statements on who suffers most are not helpful and may actually be a disservice to the fight for greater gender equality.


It should instead read − 5.94 .The authors found two minor errors in the text, abstract and Table 2:


Too much blood in terms of unemployment and sweat in terms of intellectual effort has been spent on trying to determine the amount of fiscal space that economies have — our policy focus instead should be on what to do with the fiscal space that almost all advanced economies (and a surprising number of emerging market economies) actually have.


Endocanin 22.1% . Those c


N/A C.iwatai was collected from Yunnan: Baoshan, instead of Yunnan: Menglian Dai; C.kaihuanus was collected from Yunnan: Jinghong, instead of Yunnan: Guangnan county; and C.filippovi was collected from Sichuan: Mount Emei, instead of Sichuan: Emeishan city.It has come to our attention that in the work referenced above, Figure


Second EDN3-OE ’.Molecular Medicine Reports for granting them the opportunity to publish this. The authors regret that these errors were included in the paper, and also apologize to the readership for any inconvenience caused.All the authors approve of the publication of this corrigendum, and the authors are grateful to the Editor of


Changes of immune cells in patients with hepatocellular carcinoma treated by radiofrequency ablation and hepatectomy, a pilot study. Open Life Sci. 2021;16(1):1002–9. The authors apologize to the Journal, readers, and their colleagues for the mistake and any inconvenience it caused.


To the editor,We thank the comments made by Dr. Atan regarding our manuscript “Impact of COVID-19 pandemic on a urology residency program” , 3. ThesThe Authors


N- and N,N′-alkyl indigo derivatives’ by Daniela Pinheiro et al., Chem. Sci., 2020, DOI: 10.1039/d0sc04958a.Correction for ‘Deep in blue with green chemistry: influence of solvent and chain length on the behaviour of  The authors regret that incorrect compound names and values are reported in The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers.


The caption for


The Donald P. Kent Award lecture will feature an address by the 2020 Kent Award recipient, David Ekerdt, PhD, FGSA, of the University of Kansas. The Kent Award is given annually to a member of The Gerontological Society of America who best exemplifies the highest standards of professional leadership in gerontology through teaching, service, and interpretation of gerontology to the larger society. The Robert W. Kleemeier Award lecture will feature an address by the 2020 Kleemeier Award recipient, Matt Kaeberlein, PhD, FGSA, of the University of Washington. The Kleemeier Award is given annually to a member of The Gerontological Society of America in recognition for outstanding research in the field of gerontology.


The authors wish to make the following corrections to this paper . In the Dr. SangJoon Lee has been requested by Ulsan National Institutes of Science and Technology (UNIST) that his affiliation of UNIST be removed from the Affiliations, because Dr. Lee’s position was not officially assigned by UNIST when the paper was published.2: Department of Infection Biology, Faculty of Medicine, University of Tsukuba, Ibaraki 305-8577, Japan. The corrected affiliation section should be: SangJoon LeeThe authors apologize for any inconvenience caused and state that the scientific conclusions are unaffected. The original publication has also been updated.


Following the publication of this paper, the authors have realized that they overlooked indicating that Zhikun Chen and Qin Che contributed equally to this work. Therefore, the affiliations for this paper should have been written as follows:1*, QIN CHE2* and CHUNXUE XIE3ZHIKUN CHEN1Emergency, 2Infectious Diseases and 3General Practice, Jingmen No. 1 People's Hospital, Jingmen, Hubei 448000, P.R. ChinaDepartments of *Contributed equallyThe authors confirm that there are no further errors in the study, and all the authors agree to this correction. The authors regret their oversight, and apologize for any inconvenience caused.


In the current version of the Table S13, we have listed the correct values. The correction of this error does not affect any of the reported results or conclusions of the paper but nevertheless should be stated correctly. The authors sincerely apologize to the readers for this unintended lack of thoroughness and any confusion that may have resulted from that.


Retraction Note: Rice 14, 32 (2021)https://doi.org/10.1186/s12284-021-00474-zThe authors have retracted this article. Following publication, errors were discovered in Figure 1, Figure 5 and Table 1. The authors have stated that the phenotypic characterization of oslil3 mutant still needs further experiments to analyze the intermediate metabolites in carotene biosynthesis such as the contents of alfa-carotene and beta-carotene, and that the analysis of oslil3 mutant is not precisely described. In addition, the authors have stated that they need to further analyze the protein accumulation levels of OsPSYs in the mutant as compared with the WT via the PSYs specific antibodies to more accurately validate the interaction between LIL3 and PSYs. The authors intend to resubmit a revised manuscript. All authors agree with this retraction.


This abstract has been withdrawn.


Page 2: In the Fig. 1 legend, line 11, “reverse transcription [RT]” should read “retention time [RT].”Volume 6, no. 5, e00585-21, 2021,


The affiliation for the fourth author is incorrect. Nikita B. Gudimchuk is not affiliated with #3 but with #2. The full affiliation for Nikita B. Gudimchuk is as follows:1 Department of Physics, Lomonosov Moscow State University, Moscow, Russia, 2 Center for Theoretical Problems of Physicochemical Pharmacology, Moscow, Russia, 4 Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia


Rhizoctonia solani by Malik et al.(2019) should be Arshi Malik (2019)Bioinformation. 2019 15:227. PMID: 31285645The first author in "Molecular docking and pharmacokinetic evaluation of natural compounds as targeted inhibitors against Crz1 protein in


We are issuing this expression of concern in consultation with the publisher to fulfil their reporting obligation regarding the publication  mentioneOne of the authors has raised concerns regarding the methodology employed in the study, the conclusions drawn and the insufficient consideration of laboratory staff and resources. In order to keep the highest scientific standards, an in-depth investigation is initiated by the responsible editors together with the journal’s editorial office in collaboration with the editorial board, and in accordance with the Committee on Publication Ethics (COPE) guidance. The article will be updated and any necessary corrections made at the conclusion of the investigation process.


The authors of  would liAudie L. Murphy Division, South Texas Veterans Health Care System, San Antonio, TX 78229, USA.


In Chenggui Wang,1


When this paper first published, it was missing the below conflict of interest statements from the authors. These conflict of interest statements now appear in the paper online.Dr Patrick Blin wishes to record that he is an employee of the Bordeaux PharmacoEpi team in the University of Bordeaux, and the studies were performed by this team at the request of the French Health Technology Assessment agency, with a grant from Lundbeck and according to the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCEEP) code of conduct and independence.Dr François Paille wishes to record that he has received payments for consulting activity  and for invitations to speak at conferences connected with Lundbeck, Indivior and Pfizer.


There is an error in


The authors declare that a patent application entitled “Cell-based vehicles for potentiation of viral therapy” has been filed on August 8, 2019 by the inventors Dobrin Draganov and Aladar A. Szalay [


The Editorial Office has been made aware of potential issues surrounding the scientific validity of this paper, hence has issued an expression of concern to notify readers whilst the Editorial Office investigates.


The authors wish to make the following changes to the published paper  as listecis-1,4-isoprene) were wrongly labelled and have been corrected as shown below.Chemical structures for poly(ß-oxidation should be replaced by oxiAB.oxiAB should be replaced by ß-oxidation.In the original manuscript,


In


The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a satisfactory response. The Editor apologizes to the readership for any inconvenience caused.Following the publication of this paper, the authors contacted the office to inform us that they had made errors in the compilation of the tumour images shown in Fig. 4A. Further to the contact we received from these authors, an independent enquiry was conducted in the Editorial office, after which we were able to ascertain that the data in question had appeared in slightly modified form in another publication written by different authors 6 years previously. Owing to the fact that the contentious data in the above article had already been published elsewhere prior to its submission to


HemaSphere. 2020;4:e356), the authors requested a change to their selected Creative Commons (CC) license. The license previously chosen was CC BY-NC-ND, but is now CC BY to comply with funding mandates. This adjustment has been made and does not affect the outcome of this publication.Since the publication of the article entitled “Rapid Emergence of Chronic Lymphocytic Leukemia During JAK2 Inhibitor Therapy in a Patient With Myelofibrosis” (https://journals.lww.com/hemasphere/Fulltext/2020/06000/Rapid_Emergence_of_Chronic_Lymphocytic_Leukemia.9.aspxThe change has been made online:


We welcome feedback from the authors Deng and Qin through their comment  on our pThank you for considering our response to the comment.


Under “Assessment of Metals in Maternal Urine,” the sentence on the limits of detection now reads as follows: “The limits of detection were 0.399 μg/L for arsenic, 0.066 μg/L for cadmium, 0.022 μg/L for lead, 0.016 μg/L for cobalt, 0.225 μg/L for copper, 0.090 μg/L for nickel, 0.008 μg/L for thallium, and 0.417 μg/L for zinc.” This article has been corrected.1In the Original Investigation titled “Association Between Prenatal Exposure to Metals and Atopic Dermatitis Among Children Aged 4 Years in Taiwan,”


The final author in the author list, Professor Akio Matsubara , contacted the Editorial Office to say that he should not have been listed as an author in this published article. His inclusion as an author on the paper arose as a misunderstanding on the part of some of the other authors.The revised authorship on the paper is shown above, now excluding Akio Matsubara. All the remaining authors agree with the revision made to the authorship on this paper, and the authors remaining on the paper apologize for any inconvenience caused. Therefore, the revised authors’ names and affiliations in this paper are as follows:1, Daiki Murata2, Shogo Inoue1, Tetsutaro Hayashi1, Koji Mita2, Yasuhisa Hasegawa3, Masao Kato4, Mitsuru Kajiwara5, Masanobu Shigeta6, Satoshi Maruyama7, Hiroyuki Moriyama8 and Seiji Fujiwara9Jun Teishima1Department of Urology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551; 2Department of Urology, Hiroshima-City Asa Citizens Hospital, Hiroshima 731-0293; 3Department of Urology, Fukuyama Medical Center, Fukuyama, Hiroshima 720-8520; 4Department of Urology, Hiroshima General Hospital, Hatsukaichi, Hiroshima 738-8503; 5Department of Urology, Hiroshima Prefectural Hospital, Hiroshima 734-8530; 6Department of Urology, Kure Medical Center and Chugoku Cancer Center, Kure, Hiroshima 737-0023; 7Department of Urology, Miyoshi Central Hospital, Miyoshi, Tokushima 728-8502; 8Department of Urology, Onomichi General Hospital, Onomichi, Hiroshima 722-8508; 9Department of Urology, Higashi-Hiroshima Medical Center, Higashi-Hiroshima, Hiroshima 739-0041, Japan


Correction to: Microbiome 10, 8 (2022)https://doi.org/10.1186/s40168-021-01202-xFollowing publication of the original article , the autFrom: "JP, ML, and ZL designed the experiment; WX collected the samples, with the contribution of ZS and CD; JP and ZC performed the informatics work; JP, LL, and ML wrote the paper, with the contributions from all authors."To: "JP, ML, and ZL designed the experiment; ZS and CD collected the samples; WX performed the laboratory works; JP and ZC performed the informatics works; JP, LL, and ML wrote the paper, with the contributions from all authors."The authors apologize for this error.


R. Soc. Open Sci.7, 192151 (Published 5 August 2020) (doi:10.1098/rsos.192151)This correction refers to an error in the numeric values reported in This error has no implications on the results and conclusions drawn in the publication. The paper has now been updated.


DOI: 10.1039/C9RA00302A.Correction for ‘Investigation of plasma metabolomics and neurotransmitter dysfunction in the process of Alzheimer’s disease rat induced by amyloid beta 25-35’ by Mengying Wei  The authors regret that, due to personal negligence, The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers.


In the published version of this article, there was an error in the second sentence of the section ‘Properties’.The sentence ‘It is a facultative aerobe that grows via aerobic respiration and anaerobic respiration with nitrate as the terminal electron acceptor.’ should have read ‘It is a facultative anaerobe that grows via aerobic respiration and anaerobic respiration with nitrate as the terminal electron acceptor’.The authors apologise for any inconvenience caused.