Embracing different languages and local differences:Coconstructive patient simulation strengthens host countries’clinical training in psychiatry

BACKGROUND Global education in psychiatry is heavily influenced by knowledge from Western,high-income countries,which obscures local voices and expertise.AIM To adapt a human simulation model to psychiatric education in a context that is specific to local languages and cultures.METHODS We conducted an observational study consisting of six human simulation sessions with standardized patients from two host countries,speaking their native languages,and following an adaptation of the co-constructive patient simulation(CCPS)model.As local faculty became increasingly familiar with the CCPS approach,they took on the role of facilitators—in their country’s native language.RESULTS Fifty-three learners participated:19 child and adolescent psychiatry trainees and 3 faculty members in Türkiye(as a group that met online during 3 consecutive months);and 24 trainees and 7 faculty in Israel(divided into 3 groups,in parallel in-person sessions during a single training day).Each of the six cases reflected local realities and clinical challenges,and was associated with specific learning goals identified by each case-writing trainee.CONCLUSION Human simulation has not been fully incorporated into psychiatric education:The creation of immersive clinical experiences and the strengthening of reflective practice are two areas ripe for development.Our adaptations of CCPS can also strengthen local and regional networks and psychiatric communities of practice.Finally,the model can help question and press against hegemonies in psychiatric training that overshadow local expertise.

Coal Rock Condition Detection Model Using Acoustic Emission and Light Gradient Boosting Machine

Coal rock mass instability fracture may result in serious hazards to underground coal mining.Acoustic emissions(AE)stimulated by internal structure fracture should carry lots of favorable information about health condition of rock mass.AE as a sensitive non-destructive test method is gradually utilized to detect anomaly conditions of coal rock.This paper proposes an improved multi-resolution feature to extract AE waveform at different frequency resolutions using Coilflet Wavelet Transform method(CWT).It is further adopt an efficient Light Gradient Boosting Machine(LightGBM)by several cascaded sub weak classifier models to merge AE features at different views of frequency for coal rock anomaly damage recognition.The results denote that the proposed method achieves excellent recognition performance on anomaly damage levels of coal rock.It is an effective method to detect the critical stability further to predict the rock mass bursting in time.

Analysis and validation of diagnostic biomarkers and immune cell infiltration characteristics in pediatric sepsis by integrating bioinformatics and machine learning

Background Pediatric sepsis is a complicated condition characterized by life-threatening organ failure resulting from a dysregulated host response to infection in children.It is associated with high rates of morbidity and mortality,and rapid detection and administration of antimicrobials have been emphasized.The objective of this study was to evaluate the diagnostic biomarkers of pediatric sepsis and the function of immune cell infiltration in the development of this illness.Methods Three gene expression datasets were available from the Gene Expression Omnibus collection.First,the differentially expressed genes(DEGs)were found with the use of the R program,and then gene set enrichment analysis was carried out.Subsequently,the DEGs were combined with the major module genes chosen using the weighted gene co-expression network.The hub genes were identified by the use of three machine-learning algorithms:random forest,support vector machine-recursive feature elimination,and least absolute shrinkage and selection operator.The receiver operating characteristic curve and nomogram model were used to verify the discrimination and efficacy of the hub genes.In addition,the inflammatory and immune status of pediatric sepsis was assessed using cell-type identification by estimating relative subsets of RNA transcripts(CIBERSORT).The relationship between the diagnostic markers and infiltrating immune cells was further studied.Results Overall,after overlapping key module genes and DEGs,we detected 402 overlapping genes.As pediatric sepsis diagnostic indicators,CYSTM1(AUC=0.988),MMP8(AUC=0.973),and CD177(AUC=0.986)were investigated and demonstrated statistically significant differences(P<0.05)and diagnostic efficacy in the validation set.As indicated by the immune cell infiltration analysis,multiple immune cells may be involved in the development of pediatric sepsis.Additionally,all diagnostic characteristics may correlate with immune cells to varying degrees.Conclusions The candidate hub genes(CD177,CYSTM1,and MMP8)were identified,and the nomogram was constructed for pediatric sepsis diagnosis.Our study could provide potential peripheral blood diagnostic candidate genes for pediatric sepsis patients.

Recovery rates of persistent post-COVID-19 olfactory dysfunction using psychophysical assessment:A longitudinal cohort study

Objectives:Persistent olfactory dysfunction(OD)following loss of smell associated with SARS-CoV-2 infection is a major feature of long COVID.Perspectives on the prevalence of persistent OD predominantly rely on self-reported olfactory function.Few studies have tracked longitudinal rates of recovery using psychophysical assessment among patients presenting for evaluation of persistent OD beyond a window of acute recovery.Data anchored in standardized testing methods are needed to counsel patients who fail to acutely regain their sense of smell.This study aims to quantify the degree of persistent OD in post-COVID-19 patients who experience subjective and psychophysical OD.Methods:We grouped participants presenting for OD evaluation into cohorts based on both subjective and psychophysical olfactory status at a baseline assessment and assessed their olfactory abilities with a visual analogue scale and the Sniffin'Sticks extended test at baseline and 1-year time points.Participants had confirmed a history of COVID-19 by lab evaluation or clinical diagnosis if lab evaluation was not available.Results:Baseline olfactory evaluation was completed by 122 participants,53 of whom completed the 1-year follow-up assessment.Among participants presenting with perceived OD,74.5%had confirmed psychophysical OD at baseline,with 55.1%at 1-year follow-up.Participants had reliable trends in self-rated versus psychophysically tested olfactory function at both time points.The total threshold,discrimination,and identification(TDI)score improved by+3.25 points in the cohort with psychophysical OD(p=0.0005),with this improvement largely attributable to an increase in median threshold scores(+2.75 points;p=0.0004).Conclusions:OD persists in a significant number of patients who fail to acutely recovery their sense of smell after COVID-19,with many demonstrating lingering deficits at 1-year.Improvements in threshold,but not discrimination or identification,most significantly mediate improvement of total TDI score at follow-up.

Stem cell-derived exosomes-an emerging tool for myocardial regeneration

Cardiovascular diseases(CVDs) continue to represent the number one cause of death and disability in industrialized countries. The most severe form of CVD is acute myocardial infarction(AMI), a devastating disease associated with high mortality and disability. In a substantial proportion of patients who survive AMI, loss of functional cardiomyocytes as a result of ischaemic injury leads to ventricular failure, resulting in significant alteration to quality of life and increased mortality. Therefore, many attempts have been made in recent years to identify new tools for the regeneration of functional cardiomyocytes. Regenerative therapy currently represents the ultimate goal for restoring the function of damaged myocardium by stimulating the regeneration of the infarcted tissue or by providing cellsthat can generate new myocardial tissue to replace the damaged tissue. Stem cells(SCs) have been proposed as a viable therapy option in these cases. However, despite the great enthusiasm at the beginning of the SC era, justified by promising initial results, this therapy has failed to demonstrate a significant benefit in large clinical trials. One interesting finding of SC studies is that exosomes released by mesenchymal SCs(MSCs) are able to enhance the viability of cardiomyocytes after ischaemia/reperfusion injury, suggesting that the beneficial effects of MSCs in the recovery of functional myocardium could be related to their capacity to secrete exosomes. Ten years ago, it was discovered that exosomes have the unique property of transferring miRNA between cells, acting as miRNA nanocarriers. Therefore, exosomebased therapy has recently been proposed as an emerging tool for cardiac regeneration as an alternative to SC therapy in the post-infarction period. This review aims to discuss the emerging role of exosomes in developing innovative therapies for cardiac regeneration as well as their potential role as candidate biomarkers or for developing new diagnostic tools.

Epigenetic regulation in major depression and other stressrelated disorders: molecular mechanisms, clinical relevance and therapeutic potential

Major depressive disorder(MDD)is a chronic,generally episodic and debilitating disease that affects an estimated 300 million people worldwide,but its pathogenesis is poorly understood.The heritability estimate of MDD is 30–40%,suggesting that genetics alone do not account for most of the risk of major depression.Another factor known to associate with MDD involves environmental stressors such as childhood adversity and recent life stress.Recent studies have emerged to show that the biological impact of environmental factors in MDD and other stress-related disorders is mediated by a variety of epigenetic modifications.These epigenetic modification alterations contribute to abnormal neuroendocrine responses,neuroplasticity impairment,neurotransmission and neuroglia dysfunction,which are involved in the pathophysiology of MDD.Furthermore,epigenetic marks have been associated with the diagnosis and treatment of MDD.The evaluation of epigenetic modifications holds promise for further understanding of the heterogeneous etiology and complex phenotypes of MDD,and may identify new therapeutic targets.Here,we review preclinical and clinical epigenetic findings,including DNA methylation,histone modification,noncoding RNA,RNA modification,and chromatin remodeling factor in MDD.In addition,we elaborate on the contribution of these epigenetic mechanisms to the pathological trait variability in depression and discuss how such mechanisms can be exploited for therapeutic purposes.

Rapid retinal functional testing

The most prominent causes of loss of vision in individuals over 50 years include age-related macular degeneration(AMD),glaucoma,and diabetic retinopathy(DR).While it is important to screen for these diseases effectively,current eye care is not properly doing so for much of the population,resulting in unfortunate visual disability and high costs for patients.Innovative functional testing can be unified with other screening methods for a more robust and safer screening and prediction of disease.The goal in the creation of functional testing modalities is to develop highly sensitive screening tests that are easy to use,accessible to all users,and inexpensive.The tests herein are deployed on an iPad with easily understood and intuitive instructions for rapid,streamlined,and automatic administration.These testing modalities could become highly sensitive screenings for early detection of potentially blinding diseases.The applications from our collaborators at AMA Optics include a cone photostress recovery test for detection of AMD and diabetic macular edema(DME),brightness balance perception for optic nerve dysfunction and especially glaucoma,color vision testing which is a broad screening tool,and visual acuity test.Machine learning with the combined structural and functional data will optimize identification of disease and prediction of outcomes.Here,we review and assess various tests of visual function that are easily administered on a tablet for screening in primary care.These user-friendly and simple screening tests allow patients to be identified in the early stages of disease for referral to specialists,proper assessment and treatment.

Vibration-controlled Transient Elastography for Assessment of Liver Fibrosis at a USA Academic Medical Center

Background and Aims:Vibration-controlled transient elastography(VCTE)is a noninvasive tool that uses liver stiffness measurement(LSM)to assess fibrosis.Since real-life data during everyday clinical practice in the USA are lacking,we describe the patterns of use and diagnostic performance of VCTE in patients at an academic medical center in New York City.Methods:Patients who received VCTE scans were included if liver biopsy was performed within 1 year.Diagnostic performance of VCTE in differentiating dichotomized fibrosis stages was assessed via area under the receiver operating characteristics(AUROC).Fibrosis stage determined from VCTE LSM was compared to liver biopsy.Results:Of 109 patients,49 had nonalcoholic fatty liver disease,16 chronic hepatitis C,15 congestive hepatopathy,and 22 at least two etiologies.AUROC was 0.90 for differentiating cirrhosis(stage 4)with a positive predictive value(PPV)range of 0.28 to 0.45 and negative predictive value range of 0.96 to 0.98.For 31(32%)patients,VCTE fibrosis stage was at least two stages higher than liver biopsy fibrosis stage.Thirteen of thirty-five pa-tients considered to have cirrhosis by VCTE had stage 0 to 2 and 12 stage 3 fibrosis on liver biopsy.Conclusions:VCTE has reasonable diagnostic accuracy and is reliable at ruling out cirrhosis.However,because of its low PPV,caution must be exercised when used to diagnose cirrhosis,as misdiagnosis can lead to unnecessary health care interventions.In routine practice,VTCE is also sometimes performed for disease etiologies for which it has not been robustly validated.

Single-chain variable fragment antibody constructs neutralize measles virus infection in vitro and in vivo

Despite the availability of an effective measles virus(MeV)vaccine and efforts to increase vaccine coverage by the WHO,UNICEF,and their partners,MeV has not been eradicated,and the estimated global measles death rose from 89,780 in 2016 to 207,500 in 2019.1 Because there is an effective measles vaccine,antiviral development for measles has not been prioritized,but recent outbreaks have highlighted the need for drugs to prevent transmission in unvaccinated populations and to protect and treat immunocompromised individuals.We identified several neutralizing mouse monoclonal antibodies(mAbs)that target the MeV fusion(F)protein in its prefusion state2 and inhibit fusion and viral infection.We engineered a single-chain variable fragment(scFv)from the most potent anti-MeV F mAb.The scFv retains the ability to inhibit fusion and prevents infection in vitro,and intranasal administration of the scFv antibody construct prevents infection in vivo.

Simulation training in endoscopic skull base surgery: A scoping review

Objective:Proficiency in endoscopic endonasal skull base surgery requires both substantial baseline training and progressive lifelong learning.Endoscopic simulation models continue to evolve in an effort to optimize trainee education and preoperative preparation and improve surgical outcomes.The current scoping review systematically reviews all available literature and synthesizes the current paradigms of simulation models for endoscopic skull base surgery training and skill enhancement.Methods:In accordance with Preferred Reporting Items for Systemic Review and Meta-Analyses guidelines,we systematically searched PubMed,Embase,CINAHL,and Cochrane databases.Studies were categorized according to the type of simulation models investigated.Results:We identified 238 unique references,with 55 studies ultimately meeting inclusion criteria.Of these,19 studies described cadaveric dissection models,17 discussed three-dimensional(3D)printed models,14 examined virtual surgical planning and augmented reality-based models,and five 5 articles described task trainers.Conclusions:There are a wide variety of simulation models for endoscopic skull base surgery,including high-fidelity cadaveric,virtual reality,and 3D-printed models.These models are an asset for trainee development and preoperative surgical preparation.

Comments on ‘An airway organoid-based screen identifies a role for the HIF1α‒glycolysis axis in SARS-CoV-2 infection’

Coronavirus disease 2019(COVID-19)has been an ongoing public health crisis since the end of 2019;besides vaccine development,there have been major research efforts focused on developing antiviral therapeutics.Remdesivir was the first US Food and Drug Administration(FDA)-approved antiviral drug for COVID-19.Subsequently,the FDA granted emergency use authorization(EUA)for three monoclonal antibody treatments,including sotrovimab or a combination of casirivimab and imdevimab,or bamlanivimab and etesevimab,each of which targets the coronavirus spike protein to block viral entry.Most recently,Britain granted conditional authorization for the ribonucleoside analog molnupiravir,developed by Merck as a viral replication inhibitor.The protease inhibitor PF-07321332 developed by Pfizer and boosted by ritonavir showed promising results in a phase III clinical trial,reducing the risk of hospitalization or death by 89%compared with placebo.

新生儿败血症

一名10日龄足月儿因呼吸急促和母乳喂养减少,转诊至急诊科。该婴儿经阴道娩出,从母婴同室出院回家。患儿回家后纯母乳喂养,每2~3小时喂养一次。婴儿母亲描述婴儿从午夜开始出现反应不好且喂养困难,6小时无尿。儿科医生发现患儿呼吸急促,80次/min,伴有鼻翼扇动。患儿血糖为55 mg/dl(3 mmol/L),肛温为36.5°C。在急诊科,完成了腰椎穿刺和血液培养,给予氨苄西林和头孢曲松抗感染治疗。11个小时后,血培养提示为无乳链球菌阳性(B组链球菌/GBS)。