Protective mechanism of TCF7L1 against retinal photoreceptor cell injury following retinitis pigmentosa based on the GEO database.

Recent studies have reported the promising value of differential gene expression analysis and weighted gene coexpression network analysis (WGCNA) for identifying disease biomarkers. Based on this method, this study intends to characterize the hub genes and pathways related to retinal photoreceptor cell (PRC) injury in the context of retinitis pigmentosa (RP). A total of 53 coexpression modules were identified by WGCNA, among which lightpink4, darkolivegreen, tan4, blue2, skyblue2, and navajowhite2 ranked at the top. By analyzing the RP microarrays retrieved from the GEO database, 338 differentially expressed genes (DEGs) were identified in the RP samples. Forty-five candidate genes were selected from these DEGs by intersection with the genes in the coexpression modules. These intersection genes were subjected to GO and KEGG analyses. Furthermore, the genes and pathways involved in PRC damage were identified based on analyses utilizing GeneCards and STRING tools. Transcription factor 7-like 1 (TCF7L1, also called TCF3) was suggested to participate in the RP-associated PRC damage through the Wnt signaling pathway. It was validated in a blue light-irradiated cell model that TCF7L1 overexpression boosted PRC viability and repressed apoptosis. Inhibition of the Wnt signaling pathway also contributed to protective effects. Together, the data mentioned above supported the conclusion that either elevation of TCF7L1 or blockade of the Wnt signaling pathway could prevent RP progression by protecting PRCs from damage.

Prospective study of urinary incontinence recovery following endoscopic enucleation of the prostate.

OBJECTIVE: To investigate the clinical trajectories and identify risk factors linked to post-enucleation urinary incontinence (UI). PATIENTS AND METHODS: In this prospective study (April 2020 to March 2022) at a single institution, 316 consecutive patients receiving endoscopic enucleation due to benign prostatic enlargement were included. Patient information and perioperative details were collected. Follow-ups, from 1 to 6 months, assessed postoperative UI using International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form and a four-item pad questionnaire, classified per International Continence Society definitions. Logistic regression analysed predictors at 1 week, while generalised estimating equation assessed risk factors from 1 to 3 months postoperatively. RESULTS: Patients with a median prostate volume of 57 mL underwent enucleation, with 22.5% experiencing postoperative UI at 1 week, 5.6% at 3 months, decreasing to 1.9% at 6 months. Multivariable analysis identified age (>80 years), specimen weight (>70 g), en bloc with anteroposterior dissection, and anal tone (Digital Rectal Examination Scoring System score <3) as potential factors influencing UI. Subgroup analysis revealed that specimen weight was associated with both continuous and stress UI. Anal tone was related to both other types and stress UI, while overactive bladder symptoms were associated with urge UI. CONCLUSION: In summary, our study elucidates transient risk factors contributing to temporary post-enucleation UI after prostatectomy. Informed decisions and personalised interventions can effectively alleviate concerns regarding postoperative UI.

Atonal homolog 7 (ATOH7) confers neuroprotection for photoreceptor cells in glaucoma via inhibition of the notch pathway.

Single-cell RNA sequencing (scRNA-seq) technologies enable the profiling and analysis of the transcriptomes of single cells and hold promise for clarifying gene mechanisms at single-cell resolution. We based this study on scRNA-seq data to reveal glaucoma-related genes and downstream pathways with neuroprotection effects. The scRNA-seq datasets related to glaucoma of retinal tissue samples of human beings and Atonal Homolog 7 (ATOH7)-null mice were obtained from the GEO database. The 74 top marker genes and 20 cell clusters were obtained in human retinal tissue samples. The key gene ATOH7 was found after the intersection with genes from GeneCards data. In the ATOH7-null mouse retinal tissue samples, pseudotime inference demonstrated significant changes in cell differentiation. Moreover, mouse retinal photoreceptor cells (PRCs) were cultured and treated with lentivirus carrying oe-ATOH7 alone or in combination with Notch signaling pathway activator Jagged-1/FC, after which cell biological functions were determined. The involvement of ATOH7 in glaucoma was identified through regulating PRCs. Furthermore, ATOH7 conferred neuroprotection in PRCs in glaucoma by mediating the Notch signaling pathway. In vitro data confirmed that ATOH7 overexpression promoted the differentiation of PRCs and inhibited their apoptosis by suppressing the Notch signaling pathway. The evidence provided by our study highlighted the involvement of ATOH7 in the blockade of the Notch signaling pathway, resulting in the neuroprotection for PRCs in glaucoma.

Pemetrexed combined with dual immune checkpoint blockade enhances cytotoxic T lymphocytes against lung cancer.

Chemotherapy, in combination with immune checkpoint blockade (ICB) targeting to programmed death-1 (PD-1) or its ligand PD-L1, is one of the first-line treatments for patients with advanced non-small-cell lung cancer (NSCLC). However, a large proportion of patients, especially those with PD-L1 negative tumors, do not benefit from this treatment. This may be due to the existence of multiple immunosuppressive mechanisms other than the PD-1/PD-L1 axis. Human leukocyte antigen-G (HLA-G) has been identified as an immune checkpoint protein (ICP) and a neoexpressed tumor-associated antigen (TAA) in a large proportion of solid tumors. In this study, we evaluated the induction of HLA-G as well as PD-L1 using sublethal doses of chemotherapeutics including pemetrexed in different NSCLC cell lines. Except for gefitinib, most of the chemotherapeutic agents enhanced HLA-G and PD-L1 expression in a dose-dependent manner, whereas pemetrexed and carboplatin treatments showed the most consistent upregulation of PD-L1 and HLA-G in each cell line. In addition to protein levels, a novel finding of this study is that pemetrexed enhanced the glycosylation of HLA-G and PD-L1. Pemetrexed potentiated the cytotoxicity of cytotoxic T lymphocytes (CTLs) to treat NSCLC. Both in vitro and in vivo experiments revealed that CTL-mediated cytotoxicity was most pronounced when both anti-PD-L1 and anti-HLA-G ICBs were combined with pemetrexed treatment. In conclusion, anti-HLA-G could be an intervention strategy in addition to the anti-PD-1/PD-L1 pathway for NSCLC. Moreover, dual targeting of PD-L1 and HLA-G combined with pemetrexed might have a better extent of CTL-based immunotherapy.

Survival outcomes and prognostic factors for first-line abiraterone acetate or enzalutamide in patients with metastatic castration-resistant prostate cancer.

PURPOSE: To investigate the survival outcomes of metastatic castration-resistant prostate cancer (mCRPC) patients receiving first-line novel androgen receptor axis-targeted therapies (ARATs) and prognostic factors for patient survival. METHODS: This retrospective study obtained data from 202 patients who started abiraterone acetate or enzalutamide as first-line therapy for mCRPC between 2016 and 2021 from a single academic center. The primary endpoint was overall survival (OS) defined as the interval from the start of ARAT to death, loss to follow-up, or the end of the study period. The secondary endpoints were PSA decline, PSA nadir, and time to nadir (TTN) after ARATs. Kaplan-Meier survival analyses were applied for depicting OS. Cox proportional hazards model with inversed probability of treatment weighing-adjustment was used to validate the effect of patient, disease, and treatment response factors on OS. RESULTS: Among 202 patients, 164 patients were treated with first-line ARATs alone and 38 patients received second-line chemotherapy. The median OS was not reached in patients with first-line ARATs alone and was 38.8 months in those with subsequent chemotherapy after failure from ARATs. OS was not different between the use of abiraterone and enzalutamide, though enzalutamide showed a higher rate of PSA decline ≧ 90% (56% versus 40%, p = 0.021) and longer TTN (5.5 versus 4.7 months, p = 0.019). Multivariable analysis showed that PSA nadir > 2 ng/mL [hazard ratio (HR) 7.04, p < 0.001] and TTN<7 months (HR 2.18, p = 0.012) were independently associated with shorter OS. Patients with both of these poor prognostic factors had worse OS compared to those who had 0-1 factors (HR 9.21, p < 0.001). CONCLUSIONS: Patients with mCRPC who received first-line ARATs had better survival if they had a PSA nadir[Formula: see text]2 ng/mL or a TTN[Formula: see text]7 months. Further study is needed to determine if an early switch in therapy for those in whom neither is achieved may impact OS.

Increased pituitary volumes in patients with Sanfilippo syndrome (mucopolysaccharidosis type 3, MPS III).

PURPOSE: To evaluate apparent pituitary gland enlargement in patients with Sanfilippo syndrome observed at our institution. METHODS: Twelve patients with Sanfilippo syndrome with brain MRI were studied. Anterior, posterior, and whole pituitary volumes were estimated using the prolate ellipsoid volume calculation method (π/6 × L × W × H). Convexity along the upper pituitary margin (Elster's grade) was also measured. These values were compared to two age- and sex-matched groups (normal controls and patients with Hurler syndrome) using one-way ANOVA followed by Tukey's post hoc analysis for multiple comparisons. RESULTS: In the Sanfilippo cohort, the mean whole pituitary volume was 529.9 mm, the mean anterior pituitary volume was 333.4 mm, and the mean posterior pituitary volume was 59.1 mm with Elster's grade of 4.2. In the control cohort, the mean whole pituitary volume was 217.4 mm, the mean anterior pituitary volume was 154.8 mm, and the mean posterior pituitary volume was 28.4 mm with Elster's grade of 2.5. In the Hurler syndrome cohort, the mean whole pituitary volume was 310.0 mm, the mean anterior pituitary volume was 178.2 mm, and the mean posterior pituitary volume was 35.4 mm with Elster's grade of 3.5. CONCLUSION: In our cohort of patients with Sanfilippo syndrome, whole, anterior, and posterior pituitary volumes and degree of convexity along the upper pituitary border were all significantly greater than controls. The cause of these morphological changes is unclear, as is clinical correlation of the findings.

Microstructural and hemodynamic changes in the fundus after pars plana vitrectomy for different vitreoretinal diseases.

BACKGROUND: Pars plana vitrectomy is the standard treatment for several vitreoretinal diseases. Continuous improvements in ophthalmic surgical techniques have led to excellent postoperative recovery of the anatomic structure of the fundus. However, postoperative visual outcomes are not always satisfactory. METHODS: A literature search of articles published before 31 December 2022 was conducted on PubMed using the following keywords: "diabetic retinopathy," "rhegmatogenous retinal detachment," "idiopathic epiretinal membrane," "idiopathic macular hole," "vitrectomy," "optical coherence tomography," "optical coherence tomography angiography," "microstructure," "microstructural," "hemodynamic," "hemodynamics," and "microcirculation." Additional studies were identified by hand-searching references for relevant studies. Articles were screened for language, repetition, and relevance to the direction of study. Studies with a sample size ≥ 7 and the final follow-up time ≥ 4 weeks after vitrectomy were included in this review. Only articles published in English were included. Articles not related to our topic were excluded. Reviews and single case reports were excluded. We structured this review by disease category. The thickness of the retina and choroid, the area of the foveal avascular zone, the vessel density of the retinal and choroidal capillary plexus, and the potential association of related parameters with postoperative visual outcomes are the main outcome measures of studies included in this review. RESULTS: A total of 48 studies were included in this review. There were contradictory results regarding the association between postoperative microcirculatory parameters and visual acuity in patients with diabetic macular edema, with some studies concluding that improvement in perimacular microcirculation may be an important factor that affects visual acuity, and others concluded that postoperative improvement in visual acuity was not related to changes in macular blood flow. The results of studies on the relationship between postoperative microstructural and microcirculatory parameters and visual acuity in rhegmatogenous retinal detachment, idiopathic epiretinal membrane, and idiopathic macular hole eyes have been inconsistent. In gas tamponade macula-off rhegmatogenous retinal detachment eyes, postoperative best-corrected visual acuity has been reported to correlate positively with vessel density of deep capillary plexus and negatively with foveal avascular zone area of superficial capillary plexus and deep capillary plexus. In silicone oil tamponade macula-off rhegmatogenous retinal detachment eyes, best-corrected visual acuity has been reported to be positively correlated with the retinal thickness of the parafoveal 3 mm temporal quadrant and positively correlated with the vessel density of the superficial capillary plexus in the foveal, parafoveal, and perifoveal area. In addition, best-corrected visual acuity was worse and associated with reduced thickness of the inner retina, ganglion cell layer, outer plexiform layer, and outer nuclear layer in silicone oil tamponade rhegmatogenous retinal detachment eyes compared to gas tamponade. Postoperative best-corrected visual acuity in idiopathic epiretinal membrane eyes was positively correlated with the foveal avascular zone area but negatively correlated with full retinal thickness and inner retinal thickness in the foveal and parafoveal areas. Improvement in postoperative best-corrected visual acuity in idiopathic macular hole eyes was associated with reduced inner retinal thickness and reduced foveal avascular zone area. CONCLUSIONS: Microstructural and hemodynamic changes are involved in the recovery process after PPV for different vitreoretinal diseases. The thickness of each retinal layer in different regions of the macula, foveal avascular zone area, and vessel density of different retinal capillary plexuses in different macular regions may be potential prognostic factors for postoperative visual recovery. However, the results of the existing literature are inconsistent and require further study.

Comparative Insight into Microglia/Macrophages-Associated Pathways in Glioblastoma and Alzheimer's Disease.

Microglia and macrophages are pivotal to the brain's innate immune response and have garnered considerable attention in the context of glioblastoma (GBM) and Alzheimer's disease (AD) research. This review delineates the complex roles of these cells within the neuropathological landscape, focusing on a range of signaling pathways-namely, NF-κB, microRNAs (miRNAs), and TREM2-that regulate the behavior of tumor-associated macrophages (TAMs) in GBM and disease-associated microglia (DAMs) in AD. These pathways are critical to the processes of neuroinflammation, angiogenesis, and apoptosis, which are hallmarks of GBM and AD. We concentrate on the multifaceted regulation of TAMs by NF-κB signaling in GBM, the influence of TREM2 on DAMs' responses to amyloid-beta deposition, and the modulation of both TAMs and DAMs by GBM- and AD-related miRNAs. Incorporating recent advancements in molecular biology, immunology, and AI techniques, through a detailed exploration of these molecular mechanisms, we aim to shed light on their distinct and overlapping regulatory functions in GBM and AD. The review culminates with a discussion on how insights into NF-κB, miRNAs, and TREM2 signaling may inform novel therapeutic approaches targeting microglia and macrophages in these neurodegenerative and neoplastic conditions. This comparative analysis underscores the potential for new, targeted treatments, offering a roadmap for future research aimed at mitigating the progression of these complex diseases.

A ZFP42/MARK2 regulatory network reduces the damage of retinal ganglion cells in glaucoma: a study based on GEO dataset and in vitro experiments.

Glaucoma is a common disorder in which the death of retinal ganglion cells (RGCs) results in a progressive loss of sight, even blindness. This study was performed to reveal the key molecular mechanism of RGC damage in glaucoma based on the Gene Expression Omnibus database. Glaucoma-related microarray datasets were identified, followed by collection of differentially expressed genes (DEGs) with the key genes discovered by weighted gene co-expression network analysis. Through LASSO regression analysis, candidate genes involved in the pathogenesis of glaucoma were identified with their accuracy evaluated by receiver operating characteristic curve analysis. The glaucoma-specific transcriptional regulatory network was constructed to determine the key transcription factor regulatory axis. Then, in vitro cell models were established using H2O2 for further verifying the regulatory role of identified ZFP42/MARK2 axis in RGC damage in glaucoma. Differential analysis of GSE27276, GSE45570, and GSE101727 microarray datasets yielded 165 DEGs, and 22 key genes were identified following. Then, 9 candidate genes involved in the pathogenesis of glaucoma was collected and the key ZFP42/MARK2 regulatory axis was found. In vitro cell experiments further confirmed that ZFP42 and MARK2 were down-regulated in RGCs treated with H2O2. In addition, overexpression of ZFP42 increased the expression of MARK2 to increase RGC cell viability, and reduce cell apoptosis and ROS levels, while silencing MARK2 could reverse the protective effect of ZFP42. We confirmed that ZFP42 reduced the damage of RGCs in glaucoma by up-regulating the expression of MARK2.

Catheter-directed therapies for the treatment of high risk (massive) and intermediate risk (submassive) acute pulmonary embolism.

BACKGROUND: Acute pulmonary embolism (APE) is a major cause of acute morbidity and mortality. APE results in long-term morbidity in up to 50% of survivors, known as post-pulmonary embolism (post-PE) syndrome.  APE can be classified according to the short-term (30-day) risk of mortality, based on a variety of clinical, imaging and laboratory findings. Most mortality and morbidity is concentrated in high-risk (massive) and intermediate-risk (submassive) APE. The first-line treatment for APE is systemic anticoagulation.  High-risk (massive) APE accounts for less than 10% of APE cases and is a life-threatening medical emergency, requiring immediate reperfusion treatment to prevent death. Systemic thrombolysis is the recommended treatment for high-risk (massive) APE. However, only a minority of the people affected receive systemic thrombolysis, due to comorbidities or the 10% risk of major haemorrhagic side effects. Of those who do receive systemic thrombolysis, 8% do not respond in a timely manner. Surgical pulmonary embolectomy is an alternative reperfusion treatment, but is not widely available.  Intermediate-risk (submassive) APE represents 45% to 65% of APE cases, with a short-term mortality rate of around 3%. Systemic thrombolysis is not recommended for this group, as major haemorrhagic complications outweigh the benefit. However, the people at higher risk within this group have a short-term mortality of around 12%, suggesting that anticoagulation alone is not an adequate treatment. Identification and more aggressive treatment of people at intermediate to high risk, who have a more favourable risk profile for reperfusion treatments, could reduce short-term mortality and potentially reduce post-PE syndrome. Catheter-directed treatments (catheter-directed thrombolysis and catheter embolectomy) are minimally invasive reperfusion treatments for high- and intermediate-risk APE. Catheter-directed treatments can be used either as the primary treatment or as salvage treatment after failure of systemic thrombolysis. Catheter-directed thrombolysis administers 10% to 20% of the systemic thrombolysis dose directly into the thrombus in the lungs, potentially reducing the risks of haemorrhagic side effects. Catheter embolectomy mechanically removes the thrombus without the need for thrombolysis, and may be useful for people with contraindications for thrombolysis.  Currently, the benefits of catheter-based APE treatments compared with existing medical and surgical treatment are unclear despite increasing adoption of catheter treatments by PE response teams. This review examines the evidence for the use of catheter-directed treatments in high- and intermediate-risk APE. This evidence could help guide the optimal treatment strategy for people affected by this common and life-threatening condition. OBJECTIVES: To assess the effects of catheter-directed therapies versus alternative treatments for high-risk (massive) and intermediate-risk (submassive) APE. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search was 15 March 2022. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of catheter-directed therapies for the treatment of high-risk (massive) and intermediate-risk (submassive) APE. We excluded catheter-directed treatments for non-PE. We applied no restrictions on participant age or on the date, language or publication status of RCTs. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. The main outcomes were all-cause mortality, treatment-associated major and minor haemorrhage rates based on two established clinical definitions, recurrent APE requiring retreatment or change to a different APE treatment, length of hospital stay, and quality of life. We used GRADE to assess certainty of evidence for each outcome. MAIN RESULTS: We identified one RCT (59 participants) of (ultrasound-augmented) catheter-directed thrombolysis for intermediate-risk (submassive) APE. We found no trials of any catheter-directed treatments (thrombectomy or thrombolysis) in people with high-risk (massive) APE or of catheter-based embolectomy in people with intermediate-risk (submassive) APE. The included trial compared ultrasound-augmented catheter-directed thrombolysis with alteplase and systemic heparinisation versus systemic heparinisation alone. In the treatment group, each participant received an infusion of alteplase 10 mg or 20 mg over 15 hours. We identified a high risk of selection and performance bias, low risk of detection and reporting bias, and unclear risk of attrition and other bias. Certainty of evidence was very low because of risk of bias and imprecision.  By 90 days, there was no clear difference in all-cause mortality between the treatment group and control group. A single death occurred in the control group at 20 days after randomisation, but it was unrelated to the treatment or to APE (odds ratio (OR) 0.31, 95% confidence interval (CI) 0.01 to 7.96; 59 participants). By 90 days, there were no episodes of treatment-associated major haemorrhage in either the treatment or control group. There was no clear difference in treatment-associated minor haemorrhage between the treatment and control group by 90 days (OR 3.11, 95% CI 0.30 to 31.79; 59 participants). By 90 days, there were no episodes of recurrent APE requiring retreatment or change to a different APE treatment in the treatment or control group. There was no clear difference in the length of mean total hospital stay between the treatment and control groups. Mean stay was 8.9 (standard deviation (SD) 3.4) days in the treatment group versus 8.6 (SD 3.9) days in the control group (mean difference 0.30, 95% CI -1.57 to 2.17; 59 participants). The included trial did not investigate quality of life measures.  AUTHORS' CONCLUSIONS: There is a lack of evidence to support widespread adoption of catheter-based interventional therapies for APE. We identified one small trial showing no clear differences between ultrasound-augmented catheter-directed thrombolysis with alteplase plus systemic heparinisation versus systemic heparinisation alone in all-cause mortality, major and minor haemorrhage rates, recurrent APE and length of hospital stay. Quality of life was not assessed.  Multiple small retrospective case series, prospective patient registries and single-arm studies suggest potential benefits of catheter-based treatments, but they provide insufficient evidence to recommend this approach over other evidence-based treatments. Researchers should consider clinically relevant primary outcomes (e.g. mortality and exercise tolerance), rather than surrogate markers (e.g. right ventricular to left ventricular (RV:LV) ratio or thrombus burden), which have limited clinical utility. Trials must include a control group to determine if the effects are specific to the treatment.

MicroRNA-203 diminishes the stemness of human colon cancer cells by suppressing GATA6 expression.

The interaction between hyaluronan and CD44, an important cancer stem-cell marker, stimulates various tumor cell-specific functions such as the stemness of tumor cells. microRNA-203 (miR-203) can be downregulated by this interaction in human colorectal cancer (CRC) cells, which increases their stemness; however, the underlying mechanism is not yet defined. Here, we show that overexpression and sequestration of miR-203 in HCT-116 and HT-29 human CRC cells reduces and enhances their stemness, respectively. We also show that GATA-binding factor 6 (GATA6) is a direct target of miR-203. Our results indicate that upregulated expression of this transcription factor not only restores the self-renewal abilities of miR-203-overexpressing HCT-116 and HT-29 cells but also promotes the stemness properties of their parental counterparts. More important, we show that silencing the expression of either LRH-1 or Hes-1 is sufficient to diminish the stemness-promoting effects of GATA6 in human CRC cells. Together, our findings delineate the stemness-inhibitory mechanism of miR-203 in human CRC cells and suggest that this miR is a potential therapeutic agent for colorectal cancer.

M2-like polarization of THP-1 monocyte-derived macrophages under chronic iron overload.

Macrophages are characterized by phenotypical and functional heterogeneity. In different microenvironments, macrophages can polarize into two types: classically activated macrophages (M1) or alternatively activated macrophages (M2). M1 macrophages are a well-known bacteriostatic macrophage, and conversely, M2 macrophages may play an important role in tumor growth and tissue remodeling. M1 macrophages have been reported to have high intracellular iron stores, while M2 macrophages contain lower intracellular iron. It has been well-described that disturbances of iron homeostasis are associated with altered immune function. Thus, it is important to investigate if chronic iron overload is capable of polarizing macrophages. Human monocytic leukemia THP-1 cells were maintained in culture medium that contained 100 µM ferrous sulfate heptahydrate (FeSO4) (I-THP-1) and differentiated into THP-1-derived macrophages (I-TDMs) by induction with phorbol 12-myristate 13-acetate (PMA). We characterized that I-TDMs not only enhanced the surface expression of CD163 and CD206 but also increased arginase and decreased iNOS protein expression. I-TDMs enhanced pSTAT6 expression and decreased pSTAT1 and NF-κB expressions. Furthermore, the gene expression profile of I-TDMs was comparable with M2 macrophages by performing human oligonucleotide DNA microarray analysis. Finally, functional assays demonstrated I-TDMs secreted higher levels of IL-10 but not M1 cytokines. Additionally, the conditional medium of I-TDMs had enhanced migration and increased invasion of A375 melanoma cells which was similar to the characteristics of tumor-associated macrophages. Taken together, we demonstrated that THP-1-derived macrophages polarized to a phenotype of M2-like characteristics when subjected to chronic iron overload.

Peering Into the Black Box of Artificial Intelligence: Evaluation Metrics of Machine Learning Methods.

OBJECTIVE: Machine learning (ML) and artificial intelligence (AI) are rapidly becoming the most talked about and controversial topics in radiology and medicine. Over the past few years, the numbers of ML- or AI-focused studies in the literature have increased almost exponentially, and ML has become a hot topic at academic and industry conferences. However, despite the increased awareness of ML as a tool, many medical professionals have a poor understanding of how ML works and how to critically appraise studies and tools that are presented to us. Thus, we present a brief overview of ML, explain the metrics used in ML and how to interpret them, and explain some of the technical jargon associated with the field so that readers with a medical background and basic knowledge of statistics can feel more comfortable when examining ML applications. CONCLUSION: Attention to sample size, overfitting, underfitting, cross validation, as well as a broad knowledge of the metrics of machine learning, can help those with little or no technical knowledge begin to assess machine learning studies. However, transparency in methods and sharing of algorithms is vital to allow clinicians to assess these tools themselves.

Junctional ST-depression and tall symmetrical T-waves with an obtuse marginal artery occlusion: A case report.

A 54-year-old man presented to the emergency department with chest pain and electrocardiogram (ECG) changes of acute ST-segment elevation myocardial infarction (STEMI) and junctional ST-depression with tall symmetrical T-waves (de Winter T-wave) in the lateral and inferior leads. Emergent coronary angiography revealed a culprit lesion in the gigantic obtuse marginal artery (OM). This case demonstrates the de Winter T-wave can occur in a patient with an acute occlusion of OM. Emergency physicians, ambulance staff, cardiologists and all involved in STEMI networks should familiarize themselves with this unusual ECG pattern and consider transferring patients for urgent angiography and reperfusion therapy.

Thrombolytic therapy in a patient with chest pain with de Winter ECG pattern occurred after ST-segment elevation: A case report.

The de Winter electrocardiogram (ECG) pattern may signify proximal left anterior descending artery (LAD) occlusion and was suggested to be managed as ST-segment elevation myocardial infarction (STEMI) equivalent for urgent angiography and reperfusion therapy. However, cardiac catheter laboratory is not readily or timely available in every hospital. When timely percutaneous coronary intervention (PCI) is not available, thrombolytic therapy can be considered in patients with ongoing ischemia symptoms. Here, we present a case of a successful thrombolytic therapy with de Winter ECG pattern occurred after ST-segment elevation in a scenario which the catheter laboratory was unavailable.

A study on attentional bias and response inhibition of facial expressions in manic patients: evidence from eye movement.

Introduction: In recent years, evidence has accumulated to suggest that patients with bipolar disorder show altered processing of emotionally relevant information. However, only a few studies have examined manic patients' eye movements when processing facial expressions. Method: A free viewing task and anti-saccade task were used separately to investigate attentional bias and response inhibition while processing emotional stimuli. Data were drawn from matched samples of manic patients (n = 25) and healthy controls (n = 20). Results: The analyses of eye-movement data revealed that there was a significant difference between manic patients and healthy controls in the total duration of fixations but not in the orientation or duration of the first fixation. However, no significant differences between manic patients and healthy controls in response inhibition were detected. Conclusion: These results demonstrate that compared to healthy controls, manic patients show a deficiency in processing speed. The patients showed no attentional vigilance to happy or sad expressions but did showed avoidance of the sad expression and focused more on the happy expression in later emotion processing. There were no impairments of response inhibition detected in manic patients. Key points Abnormal processing of emotional information and having aberrant inner-experiences of emotion is a feature of bipolar disorders. Processing speed is slow in manic patients versus healthy controls. Manic patients focused lesser on sad expression than healthy controls, which suggesting an avoidance of sad expressions. The findings show that psychotherapies like CBT may be applicable to manic patients.

Cryoballoon ablation for paroxysmal atrial fibrillation in a case of persistent left superior vena cava.

BACKGROUND: Atrial fibrillation (AF) usually originates from pulmonary veins (PVs) but can also be caused by pulmonary veins outside, such as the coronary sinus (CS), the superior vena cava (SVC), and the ligament of Marshall. CASE PRESENTATION: A 69-year-old male with a history of palpitations for 10 years was referred to our institute because of its recurrence for half a day. A dynamic electrocardiogram revealed sinus rhythm (SR) and paroxysmal AF. Echocardiography demonstrated normal cardiac structure, and physical examination results were unremarkable. However, computed tomography angiography (CTA) showed a persistent left superior vena cava (LSVC) but no indication of thrombosis in the left atria. A cryoablation catheter was inserted into the PV. After the PV was successfully isolated, AF was still observed. After cardioversion was synchronized, SR was detected, but AF occurred again in less than a minute. Finally, we observed ectopic atrial electrical activity originating from the LSVC and successfully ablated it. CONCLUSIONS: An LSVC may be a substrate for initiating or perpetuating atrial arrhythmia. Cryoballoon ablation can help treat AF originating from the LSVC.

MicroRNAs as biomarkers for human glioblastoma: progress and potential.

Glioblastoma multiforme (GBM) is the most common malignant glioma. Despite innovative research efforts in tumor therapy, the outcome for most diagnosed patients remains poor; therefore, early diagnosis of GBM is the most effective method for achieving better patient outcomes. In recent years, combined research efforts including cellular, molecular, genetic, and bioinformatics methods have been used to investigate GBM, and the results show that variations in miRNA expression occur in GBM tissues and biological fluids. Some highly stable miRNAs circulate in the blood and cerebrospinal fluid (CSF) of both healthy individuals and diagnosed patients, thus raising the possibility that miRNAs may serve as novel diagnostic markers. In addition, increased understanding of the miRNA and mRNA interactions involved in GBM progression may lead to discovering predictive biomarkers, some of which are clinically relevant for targeted therapy and predicting prognosis. However, as this field is relatively new, some studies have yielded conflicting results. To progress in the field, different advanced techniques must be combined, including bioinformatics methods and molecular and cellular techniques. In addition, we must overcome the various challenges in non-invasive GBM biomarker detection. Here, we discuss the progress and potential of miRNAs as biomarkers for GBM and related signaling pathways. Studying the clinical relevance and applicability of these biomarkers may alter GBM patient diagnosis and treatment.

Relationship Between Respiratory Dynamics and Body Mass Index in Patients Undergoing General Anesthesia with Laryngeal Mask Airway (LMA) and Comparison Between Lithotomy and Supine Positions.

BACKGROUND This study aimed to compare respiratory dynamics in patients undergoing general anesthesia with a laryngeal mask airway (LMA) in lithotomy and supine positions and to validate the impact of operational position on effectiveness of LMA ventilation. MATERIAL AND METHODS A total of 90 patients (age range, 18-65 years) who underwent general anesthesia were selected and divided into supine position (SP group) and lithotomy position groups (LP group). Vital signs and respiratory dynamic parameters of the 2 groups were measured at different time points and after implantation of an LMA. The arterial blood gas was monitored at 15 min after induction. The intraoperative changes of hemodynamic indexes and postoperative adverse reactions of LMA were recorded. The possible correlation between body mass index (BMI) and respiratory dynamic indexes was analyzed. RESULTS With prolonged duration of the operation, the inspiratory plateau pressure (Pplat), inspiratory resistance (RI), and work of breathing (WOB) gradually increased, while chest-lung compliance (Compl) and partial pressure of carbon dioxide in end-expiratory gas (PetCO2) gradually decreased (all P value <0.05). The mean airway pressure (Pmean), Pplat, and expiratory resistance (Re) in the LP group were significantly higher than in the SP group (P<0.05), while the peak inspiratory flow (FImax), peak expiratory flow (FEmax), WOB, and Compl in the LP group were significantly lower than in the SP group (P<0.05). BMI was positively correlated with peak airway pressure (PIP/Ppeak), Pplat, and airway resistance (Raw) and was negatively correlated with Compl; the differences among patients in lithotomy position were more remarkable (P<0.05). CONCLUSIONS The inspiratory plateau pressure and airway resistance increased with prolonged duration of the operation, accompanied by decreased chest-lung compliance. Peak airway pressure and airway resistance were positively correlated with BMI, and chest-lung compliance was negatively correlated with BMI. Changes among patients in lithotomy position were more remarkable than those in supine position.

[Association of von Willebrand factor gene polymorphisms with coronary artery disease among ethnic southern Han Chinese].

OBJECTIVE: To assess the association of rs216293 T/G and rs1063857 T/C polymorphisms of von Willebrand factor (vWF) gene with the morbidity of coronary artery disease (CAD) and the number of involved vessels among an ethnic Han Chinese population from Zhejiang province. METHODS: A case-control study was conducted. For 246 patients and 156 unaffected controls, the frequencies of genotypes and alleles of the rs216293T/G and rs1063857T/C polymorphisms were determined, and their association with CAD and the numbers of involved vessels were assessed. RESULTS: The frequencies of G allele of rs216293 and C allele of rs1063857 were higher in the CAD patients compared with those of the controls (30.3% vs.23.7%, chi-square=4.107, P=0.043; 7.7% vs. 4.2%, chi-square=4.066, P=0.044). The G allele of the rs216293 polymorphism and C allele of the rs1063857 polymorphism were both higher in the CAD patients compared with the controls (53.7% vs.41.0%, chi-square=6.098, P=0.014; 15.4% vs. 8.3%, chi-square=4.361, P=0.037). After adjusting the influence factors by logistic regression analysis, the G allele carriers of rs216293 and the C allele carriers of rs1063857 showed an increased risk for CAD (OR=1.625, 95%CI: 1.060-2.492, P=0.026; OR=2.305, 95% CI: 1.142-4.654, P=0.040). No significant difference was detected in the frequency of both rs216293 and rs1063857 among patients with single or multiple vessels (P>0.05). CONCLUSION: The rs216293T/G and rs1063857T/C polymorphisms of the vWF gene are both associated with the risk for CAD among the selected population. The G allele of the rs216293 polymorphism and C allele of the rs1063857 polymorphism may be the genetic determinants for CAD.