Accuracy of expanded noninvasive prenatal testing for maternal copy number variations: A comparative study with CNV-seq of maternal lymphocyte DNA.

OBJECTIVE: To evaluate the accuracy of expanded noninvasive prenatal testing (NIPT) for maternal copy number variations. MATERIALS AND METHODS: Expanded NIPT was used to detect CNVs ≥2 Mb at a whole-genome scale. The threshold of maternal deletion was copy numbers (CN) ≤ 1.6, and the threshold of maternal duplication was CN ≥ 2.4. RESULTS: Of the 5440 pregnant women with successful expanded NIPT results, 28 maternal CNVs ≥2 Mb were detected in 27 pregnant women. Except for five cases reported as test failure, 23 CNVs ≥2 Mb were confirmed among the remaining 22 pregnant women by CNV-seq of maternal lymphocyte DNA. The genomic location, copy numbers and fragment size of maternal CNVs reported by expanded NIPT were consistent with the results of CNV-seq of maternal lymphocyte DNA. CONCLUSIONS: Maternal CNVs ≥2 Mb can be accurately evaluated according to the CN indicated by expanded NIPT results.

Associations of serum lead, cadmium, and mercury concentrations with all-cause and cause-specific mortality among individuals with cardiometabolic multimorbidity.

Epidemiological evidence indicates an association between exposure to toxic metals and the occurrence of cardiometabolic diseases (CMDs). However, the impact of exposure to harmful metallic elements, such as lead (Pb), cadmium (Cd), and mercury (Hg), on mortality in individuals with cardiometabolic multimorbidity (CMM) remains uncertain. Therefore, in this study, we analyzed data from 4139 adults diagnosed with CMM from the National Health and Nutrition Examination Survey 1999-2016. CMM was defined as the presence of at least two CMDs (hypertension, diabetes, stroke, and coronary artery disease). Over an average follow-up period of 9.0 years, 1379 deaths from all causes, 515 deaths related to cardiovascular disease (CVD), and 215 deaths attributable to cancer were recorded. After adjusting for potential covariates, serum Pb concentrations were not associated with all-cause, CVD, or cancer mortality. Participants exposed to Cd had an elevated risk of all-cause mortality (hazard ratio [HR], 1.23; 95 % CI, 1.16-1.30), CVD-related mortality (HR, 1.23; 95 % CI, 1.12-1.35), and cancer-related mortality (HR, 1.29; 95 % CI, 1.13-1.47). Participants with serum Hg levels in the highest quantile had lower risks of all-cause (HR, 0.64; 95 % CI, 0.52-0.80) and CVD-related (HR, 0.62; 95 % CI, 0.44-0.88) mortality than did those in the lowest quantile. Stratified analyses revealed significant interactions between serum Cd concentrations and age for CVD-related mortality (P for interaction =0.011), indicating that CMM participants aged < 60 years who were exposed to Cd were at a greater risk of CVD-related mortality. A nonlinear relationship was observed between serum Cd concentrations and all-cause (P for nonlinear relationship = 0.012) and CVD-related (P for nonlinear relationship < 0.001) mortality. Minimizing Cd exposure in patients with CMM may help prevent premature death.

The role of serum chloride ion in the prognosis of COPD.

BACKGROUND: As exacerbations of chronic obstructive pulmonary disease (COPD) are one of the leading causes of hospitalization and are associated with significant mortality, it is particularly important to accurately assess the risk of exacerbations in COPD. Most of the current clinical biomarkers are related to inflammation and few consider how ion levels affect COPD. Chloride ion, the second most abundant serum electrolyte, has been shown to be associated with poor prognoses in several diseases, but their relationship with COPD remains unclear. METHODS: In total, 105 patients with acute exacerbations of COPD were recruited. Data on clinical characteristics, lung function, blood count, blood biochemistry, relevant scales including the Clinical COPD Questionnaire (CCQ), BODE (BMI, airflow obstruction, dyspnea, exercise capacity) index and the St. George's Respiratory Questionnaire (SGRQ) were collected from all patients for statistical analysis. RESULT: There were significant differences in lung function indicators and disease severity in the low chloride ion subgroup compared with the high chloride ion subgroup. On multiple logistic regression analysis, chloride ion was an independent factor affecting lung function in COPD patients (OR = 0.808, 95% CI: 0.708 - 0.922, p = 0.002). The sensitivity of chloride ion in predicting COPD severity was 78%, the specificity was 63%, and the area under the curve was 0.734 (p < 0.001). Subgroup analysis showed that chloride ion was a stronger predictor in male and smoking patients. CONCLUSIONS: Chloride ion was a novel prognostic biomarker for COPD, and low levels of chloride ion were independently associated with exacerbations in COPD patients.

Advances of NOTCH2NLC Repeat Expansions and Associated Diseases: A Bibliometric and Meta-analysis.

The unclear pathogenic mechanisms of neurodegenerative disorders stemming from NOTCH2NLC GGC repeat expansions drive focused research. Thus, a bibliometric and meta-analysis was conducted to uncover research trends and positivity rates in NOTCH2NLC. We conducted systematic searches in the Web of Science, PubMed, Embase, and Scopus databases for studies related to NOTCH2NLC up until August 2, 2023. Information regarding countries, institutions, authors, journals, and keywords of studies included in the Web of Science was analyzed and visualized. The positivity rates of NOTCH2NLC GGC repeat expansions across all screened patients and patients' families were pooled under the random-effects model. Publication bias and its impact were examined using funnel plots, Egger's linear regression, and trim-and-fill method. The bibliometric analysis, revealing pronounced publication growth, comprised 119 studies, which came from China and Japan particularly. "Neuronal intranuclear inclusion disease" emerged as a frequently used keyword. The meta-analysis comprised 36 studies, indicating global positivity rates of 1.79% (95% CI, 0.75-3.17) for all patients and 2.00% (95% CI, 0.26-4.78) for patients' families. Subgroup analyses based on region and phenotype suggested the highest NOTCH2NLC positivity rates in Taiwan population (5.42%, 95% CI 0.08-16.89) and in leukoencephalopathy-dominant patients (8.25%, 95% CI, 3.01-15.60). Sensitivity analysis affirmed the robustness of results. In conclusion, NOTCH2NLC GGC repeat expansions exhibit rare globally, primarily in East Asia, and leukoencephalopathy-dominant patients, emphasizing regional and phenotypic distinctions. Emerging focal points in NOTCH2NLC researches underscore the need for collaborative exploration.

Automated valvular heart disease detection using heart sound with a deep learning algorithm.

Background: Insufficient clinicians' auscultation ability delays the diagnosis and treatment of valvular heart disease (VHD); artificial intelligence provides a solution to compensate for the insufficiency in auscultation ability by distinguishing between heart murmurs and normal heart sounds. However, whether artificial intelligence can automatically diagnose VHD remains unknown. Our objective was to use deep learning to process and compare raw heart sound data to identify patients with VHD requiring intervention. Methods: Heart sounds from patients with VHD and healthy controls were collected using an electronic stethoscope. Echocardiographic findings were used as the gold standard for this study. According to the chronological order of enrollment, the early-enrolled samples were used to train the deep learning model, and the late-enrollment samples were used to validate the results. Results: The final study population comprised 499 patients (354 in the algorithm training group and 145 in the result validation group). The sensitivity, specificity, and accuracy of the deep-learning model for identifying various VHDs ranged from 71.4 to 100.0%, 83.5-100.0%, and 84.1-100.0%, respectively; the best diagnostic performance was observed for mitral stenosis, with a sensitivity of 100.0% (31.0-100.0%), a specificity of 100% (96.7-100.0%), and an accuracy of 100% (97.5-100.0%). Conclusions: Based on raw heart sound data, the deep learning model effectively identifies patients with various types of VHD who require intervention and assists in the screening, diagnosis, and follow-up of VHD.

Diabetes: a potential mediator of associations between polycyclic aromatic hydrocarbon exposure and stroke.

Epidemiological evidence suggests associations between exposure to polycyclic aromatic hydrocarbons (PAHs) and cardiovascular diseases (CVD), while diabetes is a common risk factor for CVD. The present study aims to clarify the effect of high PAH exposure on diabetes and stroke in general population. A total of 7849 individuals aged 20 years or older from the National Health and Nutrition Examination Survey 2007-2016 were included in the study. The logistic regression analysis modeled the association between PAH exposure and diabetes as well as stroke. The analysis yielded odds ratios (ORs) and 95% confidence intervals (CIs). The study also evaluated the potential mediating role of diabetes in the relation between PAH exposure and stroke via mediating effect analyses. Of the 7849 eligible participants, 1424 cases of diabetes and 243 cases of stroke were recorded. After adjusting for covariates including age, gender, smoking status, drinking status, education level, marital status, physical activity, hypertension, low-density lipoprotein cholesterol, and BMI, the ORs for stroke in the highest quartile (Q4) of total urinary PAHs were 1.97 (95% CI 1.11-3.52, P = 0.022) as compared to the lowest quartile (Q1) of total urinary PAHs. The ORs for diabetes in the Q4 of total urinary PAHs were 1.56 (95% CI 1.15-2.12, P = 0.005), while the ORs between Q4 and Q1 for stroke and diabetes concerning exposure to 2-hydroxynaphthalene were 2.23 (95% CI 1.17-4.25, P = 0.016) and 1.40 (95% CI 1.07-1.82, P = 0.015), respectively. The mediation analysis found that diabetes accounted for 5.00% of the associations between urinary PAHs and the prevalence of stroke. Urinary metabolites of PAH have been linked to stroke and diabetes. Increasing the risk of diabetes may play a significant role in mediating the association between exposure to PAHs and increased risk of stroke. Monitoring and improving glucose metabolism in individuals with high exposure to PAHs may aid in reducing the prevalence of stroke.

Synthesis of Fe3O4core/MIL-100(Fe) shell nanocomposites for tumor chemo-ferroptosis combination therapy and MR imaging.

The application of both chemotherapy and ferrotherapy together has shown great potential in increasing the effectiveness of cancer treatment. To achieve such a combination, we herein have synthesized Fe3O4core/MIL-100(Fe) shell nanocomposites (FM) that can be used for tumor chemo-ferroptosis combination therapy. In these nanocomposites, the anticancer drug 10-hydroxycamptothecin (HCPT) and iron ions could be co-delivered into tumors. On one hand, the released HCPT molecules can enter the cell nucleus and bind with DNA, resulting in induction of tumor cell apoptosis. On the other hand, the iron ions could react with H2O2leading to the production of ROS through the Fenton reaction, thereby triggering tumor cell ferroptosis. Consequently, a superior antitumor effect was achieved through the combination of the apoptosis and ferroptosis. Additionally, the Fe3O4core endowed FM with high performance for magnetic resonance imaging, which further provided novel avenues for imaging guidance therapy. Therefore, we anticipate that application of these nanocomposites could have great potential in the field of tumor therapy.

Disulfiram: A novel repurposed drug for cancer therapy.

ABSTRACT: Cancer is a major global health issue. Effective therapeutic strategies can prolong patients' survival and reduce the costs of treatment. Drug repurposing, which identifies new therapeutic uses for approved drugs, is a promising approach with the advantages of reducing research costs, shortening development time, and increasing efficiency and safety. Disulfiram (DSF), a Food and Drug Administration (FDA)-approved drug used to treat chronic alcoholism, has a great potential as an anticancer drug by targeting diverse human malignancies. Several studies show the antitumor effects of DSF, particularly the combination of DSF and copper (DSF/Cu), on a wide range of cancers such as glioblastoma (GBM), breast cancer, liver cancer, pancreatic cancer, and melanoma. In this review, we summarize the antitumor mechanisms of DSF/Cu, including induction of intracellular reactive oxygen species (ROS) and various cell death signaling pathways, and inhibition of proteasome activity, as well as inhibition of nuclear factor-kappa B (NF-κB) signaling. Furthermore, we highlight the ability of DSF/Cu to target cancer stem cells (CSCs), which provides a new approach to prevent tumor recurrence and metastasis. Strikingly, DSF/Cu inhibits several molecular targets associated with drug resistance, and therefore it is becoming a novel option to increase the sensitivity of chemo-resistant and radio-resistant patients. Studies of DSF/Cu may shed light on its improved application to clinical tumor treatment.

Angiographic assessment of vein of Marshall in atrial fibrillation: Implications for identification and cannulation.

Background: The vein of Marshall (VOM) ethanol infusion improves rhythm control in atrial fibrillation (AF). The identification and cannulation of the VOM can be technically challenging. This study aimed to assess the angiographic morphology of the VOM and investigate its value in the VOM ethanol infusion. Methods: Patients with AF (n = 162) scheduled for combined catheter ablation and VOM ethanol infusion were enrolled. The VOM morphologic features in the right anterior oblique (RAO), the left anterior oblique (LAO), and the LAO cranial views were analyzed. The impact of morphology on the identification and cannulation of the VOM was investigated. Results: The VOM was identified in 159 (98.1 %) and cannulated in 150 (92.6 %) patients. The VOM identification rate in the RAO and LAO/LAO cranial view was 97.3 % and 89.3 %, respectively. Of 134 patients with VOM identification in the LAO/LAO cranial view, 104 (77.6 %) had a VOM ostium clock location (VOMoClock) of ≤3 and 3-4 o'clock. The VOM cannulation success rate in the ≤3, 3-4, 4-5, and 5-6 o'clock groups was 100 %, 92.6 %, 88.5 %, and 77.8 %, respectively (p = 0.032). The median (interquartile range) cannulation time in the four groups was 10.5 (6.3), 12.0 (9.0), 13.0 (23.0), and 34.0 (30.0) minutes, respectively (p < 0.001). The diameter of the coronary sinus ostium in the RAO view and the VOMoClock were independent predictors for difficult cannulation. Conclusions: The VOM morphologic features in different angiographic views provide valuable information which could facilitate the identification and cannulation of the VOM.

SGLT2 inhibitors for the prevention of atrial fibrillation: a systemic review and meta-analysis.

AIMS: Sodium-glucose co-transporter-2 (SGLT2) inhibitors are reported to have cardiac benefits. The effects of SGLT2 inhibitors on the prevention of atrial fibrillation (AF) remain inconclusive. We aimed to investigate whether SGLT2 inhibitors can prevent AF occurrence in patients with cardiometabolic diseases. METHODS: We searched MEDLINE, EMBASE, and the Cochrane CENTRAL database up to July 1, 2023. Randomized, placebo-controlled trials of SGLT2 inhibitors in patients with diabetes, heart failure, chronic kidney diseases, or cardiometabolic risk factors were included. The primary outcome was AF occurrence. Relative risks (RRs) with 95% confidence intervals (CIs) were calculated in the overall population and selected subgroups. RESULTS: Forty-six trials comprising 101 100 patients were included. Overall, no significant risk reduction of AF occurrence was observed with SGLT2 inhibitors, although there was a favorable trend (RR 0.90, 95% CI 0.80-1.01). In trials with follow-up durations of over one year, a similar result was achieved (RR 0.90, 95% CI 0.80-1.01). The results were consistent across different SGLT2 inhibitors, with RRs (95%CIs) of 0.82 (0.60-1.12) for canagliflozin, 0.87 (0.73-1.03) for dapagliflozin, 0.97 (0.78-1.22) for empagliflozin, 0.99 (0.66-1.50) for sotagliflozin, and 0.87 (0.58-1.29) for ertugliflozin. Analyses in different doses of SGLT2 inhibitors yielded similar results. The associations between SGLT2 inhibitors and AF occurrence were also absent in patients with diabetes, heart failure, and chronic kidney diseases. CONCLUSION: For patients with cardiometabolic diseases or risk factors, SGLT2 inhibitors did not decrease the risk of AF occurrence, regardless of follow-up duration, type or dose of the drug, or the patient population.

The effects of SGLT2 inhibitors on the prevention of atrial fibrillation (AF) remain inconclusive. For patients with cardiometabolic diseases or risk factors, SGLT2 inhibitors did not decrease the risk of AF occurrence, regardless of follow-up duration, type or dose of the drug, or the patient population. Further research is warranted to investigate the potential benefit of SGLT2 inhibitors in AF.

Research progress of ferroptosis in Parkinson's disease: a bibliometric and visual analysis.

Background: In recent years, the role of ferroptosis in Parkinson's disease (PD) has become a research hotspot based on evidence of abnormal iron deposition and lipid peroxidation damage in the brains of PD patients. This study aims to examine the relevant research on ferroptosis and PD from a bibliometric perspective. Methods: Original research and review articles related to ferroptosis and PD were retrieved from the Web of Science Core Collection (WOSCC) database. Statistical analysis and visualization of information including countries, institutions, authors, journals, and keywords of the included studies were conducted using the R software package "bibliometrix." Results: A total of 414 articles met the inclusion criteria, averaging 37.86 citations per article. From 2012 to 2022, the average annual growth rate of research in this area was 63.44%. The corresponding authors of published articles were mainly affiliated with institutions in China, the United States, and Australia. Shanghai Jiao Tong University in China and the University of Melbourne in Australia emerged as the most active and influential institutions. The journal with the highest H-index and publication output was Free Radical Biology and Medicine. "Ferroptosis," "immunotherapy," "prognosis" and "microenvironment" were identified as high-frequency keywords, indicating current and future research directions in this field. Conclusion: This bibliometric study provides insights into current research hotspots and emerging trends in the growing field of ferroptosis research related to PD. The high-frequency keywords identified highlight active areas of investigation involving methods, mechanisms, and populations of interest.

Double-wire technique to facilitate vein of Marshall cannulation and ethanol infusion in atrial fibrillation: a case series.

BACKGROUND: The vein of Marshall (VOM) ethanol infusion is increasingly performed in combination with catheter ablation in atrial fibrillation (AF). The cannulation of the VOM can sometimes be challenging. This study aimed to evaluate the double-wire technique in cases of difficult cannulation of the VOM. CASE PRESENTATION: Patients with AF scheduled for combined catheter ablation and VOM ethanol infusion were consecutively enrolled. The procedure was performed via the femoral vein. If the regular cannulation technique with one angioplasty wire failed or took more than 20 min, the double-wire technique using a stabilizing wire and a cannulation wire was performed. The unique technique was used mainly in two scenarios, when the Eustachian ridge was too prominent as a barrier for catheter manipulation or when the VOM ostium was close to the coronary sinus ostium. Of 162 patients scheduled for VOM ethanol infusion, the double-wire technique was applied in 6 (3.7%) patients and led to a 100% successful cannulation rate of the VOM. Of the six patients, two had a prominent Eustachian ridge, and four had a VOM ostium close to the coronary sinus ostium. The mean cannulation time was 33.3 ± 7.3 min. The ethanol infusion was successfully performed in 5 patients. One patient had a collateral circulation in the distal VOM, and ethanol infusion was not performed. CONCLUSIONS: The double-wire technique can facilitate VOM cannulation and ethanol infusion in challenging cases. WORD COUNT: 231.

Is There an Association Between Parkinson's Disease and Periodontitis? A Systematic Review and Meta-Analysis.

BACKGROUND: Multiple observational studies have yielded controversial results regarding the association between Parkinson's disease (PD) and periodontitis. OBJECTIVE: This systematic review and meta-analysis was conducted to ascertain their bidirectional relationship. METHODS: A literature search for relevant studies was performed in PubMed, EMBASE, the Cochrane Library, and Web of Science databases from inception to December 19, 2022. Effect sizes (ES) with 95% confidence intervals were pooled under the random-effects model. Then, leave-one-out sensitivity analysis and contour-enhanced funnel plot were applied to assess the stability of the results. RESULTS: A total of 34 studies and 24 studies were included for systematic review and quantitative meta-analysis, respectively. Pooled ES indicated that periodontitis was not significantly associated with PD risk (HR = 1.13, 95% CI 0.88-1.45, n = 3; OR = 1.94, 95% CI 0.55-6.90, n = 7), while the Mendelian randomization study revealed no association between PD and periodontitis risk (coefficient [B] = -0.0001, standard error = 0.0001, p = 0.19). Furthermore, PD patients exhibited higher levels of periodontal pocket depth (SMD = 1.10, 95% CI 0.53-1.67), clinical attachment level (SMD = 1.40, 95% CI 0.55-2.26), plaque index (SMD = 0.81, 95% CI 0.22-1.39), and Oral Health Impact Profile-14 score (SMD = 0.91, 95% CI 0.33-1.49) compared to healthy controls. CONCLUSIONS: Our meta-analysis identified no bidirectional association between PD risk and periodontitis risk, though the prevalence of periodontitis and poorer oral status was higher in PD patients.

Noninvasive screening of fetal RHD genotype in Chinese pregnant women with serologic RhD-negative phenotype.

BACKGROUND: Noninvasive fetal RHD genotyping has been provided to nonimmunized RhD-negative pregnant women to guide anti-D prophylaxis. Among the Chinese, more than 30% of the RhD-negative phenotype is associated with variant RHD alleles, which would limit the accuracy of fetal RHD status prediction; thus, more targeting and proper programs need to be developed. STUDY DESIGN AND METHODS: Fluorescence quantitative polymerase chain reaction PCR (qPCR) or Sanger sequencing on all RHD exons was used to detect maternal RHD genotypes. For pregnant women with RHD*01N.01 or RHD*01N.03 alleles, the presence of RHD exons 5 and 10 in cell-free DNA was determined by qPCR. For pregnant women with the RHD(1227G>A) allele, high-throughput sequencing on exon 9 of the RHD gene and RHCE gene was used to predict fetal RhD phenotype. RESULTS: Among 65 cases of Chinese pregnant women with the serologic RhD-negative phenotype, three major genotypes were identified: RHD*01N.01/RHD*01N.01 (61.5%), RHD*01N.01/RHD(1227G>A) or RHD*01N.03/RHD(1227G>A) (20%), and RHD*01N.01/RHD*01N.03 (13.8%), along with three cases of minor genotypes (4.6%). For 43 pregnant women with the RHD*01N.01 or RHD*01N.03 alleles, qPCR on maternal cell-free DNA yielded a 98.5% (42/43) accuracy rate and 100% successful prediction rate. High-throughput sequencing was successfully used to predict fetal RhD phenotypes for 13 pregnant women with RHD(1227G>A). CONCLUSION: On the basis of maternal RHD genotyping, fetal genotyping through qPCR or high-throughput sequencing can improve the accuracy and success rate of prenatal fetal RhD phenotype prediction among Chinese pregnant women. It plays a potential role in guiding anti-D prophylaxis and pregnancy management in Chinese pregnant women.

Neurofilament light chain as a mediator between LRRK2 mutation and dementia in Parkinson's disease.

Elevated neurofilament light chain (NfL) levels have been associated with dementia in idiopathic Parkinson's disease (iPD). To examine the baseline and longitudinal changes in NfL levels in GBA-PD, SNCA-PD, and LRRK2-PD and further investigate the association between these genetic mutations, NfL, and dementia in PD. We analyzed data from the Parkinson's Progression Markers Initiative (PPMI), including 184 healthy controls (HC) and 617 PD categorized as iPD (n = 381), LRRK2-PD (n = 142), GBA-PD (n = 76) and SNCA-PD (n = 18). Analysis of covariance (ANCOVA) or linear mixed-effect models were used to compare the baseline or dynamic NfL levels between groups. We then explored the relationship between genetic mutations, serum NfL levels, and conversion to dementia using mediation analysis. After adjusting for confounding factors, SNCA-PD exhibited higher baseline serum NfL levels than iPD. Regarding longitudinal changes, SNCA-PD showed the highest increase rate in estimated NfL levels (2.43 pg/mL per year), while LRRK2-PD experienced the slowest increase rate (0.52 pg/mL per year). Mediation analysis indicated that higher estimated NfL level changes were associated with faster cognitive decline (ß = 0.591, p = 0.026). Specifically, the relationship between LRRK2 and dementia was mediated by the estimated NfL level change (ß = -0.717, p < 0.05). Longitudinal changes in serum NfL levels may serve as a biomarker for cognitive decline in Parkinson's disease. Moreover, compared to iPD, the slower progression of dementia in LRRK2-PD may be partially attributed to a slower increase in NfL levels.

Venous anatomy of the left ventricular summit region: Insights from high-speed rotational retrograde angiography.

INTRODUCTION: Mapping and ablation through the coronary venous system (CVS) have shown potential for ventricular arrhythmias originating from the left ventricular summit (LVS). Multielectrode catheters and balloons are frequently used for mapping and venous ethanol ablation (VEA). However, there is limited data on the venous size and drainage condition in the LVS region. This study aimed to investigate the morphology, angiographic size, and drainage condition of LV summit veins via high-speed rotational angiography (RA). METHODS: We measured and analyzed the size of the great cardiac vein (GCV), the anterior interventricular vein (AIV), veins near to the LVS, and other main tributaries of CVS in 102 patients undergoing electrophysiology study. RESULTS: Rotational retrograde angiography of LVS was successfully performed in 81 patients. The diameter of GCV at the level of the Vieussens valve and the distal end of GCV (junction of GCV-AIV) was larger in males than females (6.8 ± 1.1 vs. 5.6 ± 1.2 mm, p < .001; 5.2 ± 0.9 vs. 4.6 ± 0.8, p = .002, respectively) while no significant gender differences were observed in other tributaries. The LV summit veins presented downward drainage direction in half of the patients, indicating potential anatomic adjacency with His bundle. Left anterior oblique (LAO) 45° projection might provide the practical and optimal view of the LV summit veins. CONCLUSIONS: The coronary veins of the LVS region present various anatomical morphologies and ostium sizes. We provide a systematic description and angiographic size spectrum of CVS. RA could facilitate assessing the feature of CVS comprehensively.

Vegetation browning: global drivers, impacts, and feedbacks.

As global climate conditions continue to change, disturbance regimes and environmental drivers will continue to shift, impacting global vegetation dynamics. Following a period of vegetation greening, there has been a progressive increase in remotely sensed vegetation browning globally. Given the many societal benefits that forests provide, it is critical that we understand vegetation dynamic alterations. Here, we review associative drivers, impacts, and feedbacks, revealing the complexity of browning. Concomitant increases in browning include the weakening of ecosystem services and functions and alterations to vegetation structure and species composition, as well as the development of potential positive climate change feedbacks. Also discussed are the current challenges in browning detection and understanding associated impacts and feedbacks. Finally, we outline recommended strategies.

[Analysis of genetic etiology and related factors in 1 065 women with spontaneous abortions].

OBJECTIVE: To explore the genetic etiology and related factors in 1 065 women with spontaneous abortions. METHODS: All patients have presented at the Center of Prenatal Diagnosis of Nanjing Drum Tower Hospital from January 2018 to December 2021. Chorionic villi and fetal skin samples were collected, and the genomic DNA was assayed by chromosomal microarray analysis (CMA). For 10 couples with recurrent spontaneous abortions but normal CMA results for abortive tissues, non-in vitro fertilization-embryo transfer (IVF-ET) pregnancies and no previous history of live births and no structural abnormalities of the uterus, peripheral venous blood samples were collected. Genomic DNA was subjected to trio-whole exome sequencing (trio-WES). Candidate variants were verified by Sanger sequencing and bioinformatics analysis. Multifactorial unconditional logistic regression analysis was carried out to analyze the factors that may affect chromosomal abnormality in spontaneous abortions, such as the age of the couple, number of previous spontaneous abortions, IVF-ET pregnancy and history of live birth. The incidence of chromosomal aneuploidies in spontaneous abortions during the first trimester was compared in young or advanced-aged patients by chi-square test for liner trend. RESULTS: Among the 1 065 spontaneous abortion patients, 570 cases (53.5%) of chromosomal abnormalities were detected in spontaneous abortion tissues, which included 489 cases (45.9%) of chromosomal aneuploidies and 36 cases (3.4%) of pathogenic/likely pathogenic copy number variations (CNVs). Trio-WES results have revealed one homozygote variant and one compound heterozygote variants in two pedigrees, both of which were inherited from the parents. One likely pathogenic variant was detected in the patient from two pedigrees. Multifactorial unconditional Logistic regression analysis suggested that age of patient was an independent risk factor of chromosome abnormalities (OR = 1.122, 95%CI: 1.069-1.177, P < 0.001), the number of previous abortions and IVF-ET pregnancy were independent protective factors for chromosomal abnormalities (OR = 0.791, 0.648; 95%CI: 0.682-0.916, 0.500-0.840; P = 0.002, 0.001), whilst the age of husband and history of live birth were not (P > 0.05). The incidence of aneuploidies in the abortive tissues has decreased with the number of previous spontaneous abortions in young patients (χ² = 18.051, P < 0.001), but was not significantly correlated with the number of previous spontaneous abortions in advanced-aged patients with spontaneous abortions (P > 0.05). CONCLUSION: Chromosomal aneuploidy is the main genetic factor for spontaneous abortion, though CNVs and genetic variants may also underlie its genetic etiology. The age of patients, number of previous abortions and IVF-ET pregnancy are closely associated with chromosome abnormalities in abortive tissues.

The predictive value of tissue response viewer for lesion transmurality in a porcine model.

BACKGROUND: The tissue response viewer (TRV) is a multiparametric index that incorporates time, power, tissue pressure, impedance, and wall thickness data during radiofrequency catheter ablation (RFCA) and is used to predict the transmurality of lesions. This study aimed to evaluate the feasibility and accuracy of the TRV in a porcine model. METHODS: Twelve pigs underwent preablation high-density voltage and activation mapping of two atria, and both were repeated after linear RFCA. Intentional gaps were kept in the left atrium (LA) and were touched up in the right atrium (RA). Standard and high powers were, respectively, performed in the LA ablation. Six pigs were immediately sacrificed for pathological examination after the mapping and ablation procedure (acute study). Another six pigs were kept for 4 weeks before remapping and pathological examination (chronic study). RESULTS: All animals completed the planned procedure. The TRV function showed a sensitivity of 97.1% and a specificity of 76.9% in the acute study, and a sensitivity of 95.9% and a specificity of 72.5% in the chronic study to predict the transmural lesion. All positive and negative predictive values were over 80%. In addition, the TRV achieved higher sensitivity (92.3% vs. 85.0%) and specificity (88.2% vs. 78.9%) to predict the transmural lesion in LA ablation with high power compared with standard ablation. CONCLUSIONS: This study presents the histopathological validation of TRV to predict transmural lesions. The use of TRV may guide a more individual ablation and a more precise touch-up of gaps for atrial arrhythmias.

Transformation of Cemento-Ossifying Fibroma into Osteosarcoma after Radiotherapy and Nine Endoscopic Surgeries.

Cemento-ossifying fibromas (COFs) are benign fibro-osseous tumors usually found in the mandible and maxilla that can show malignancy in rare situations. COFs usually grow slowly and asymptomatically until they produce local bulges, pain, headaches, and visual impairment, and have a Ki-67 index within 3%, even in aggressive and recurrent cases. Surgical resection can usually provide a satisfactory prognosis. However, no cases of COF transforming into osteosarcoma have been reported. We present a case of COF involving a 58-year-old woman whose initial symptom was hearing loss in the right ear accompanied by tinnitus. Enhanced magnetic resonance imaging revealed a 3.1 cm x 3.2 cm mass centered on the right pterygoid process of the sphenoid bone. Postoperative pathology revealed a COF with a high Ki-67 index (8%-10%). Over the next two years, the tumor relapsed repeatedly. The patient underwent nine endoscopic surgeries and radiotherapy. The sixth postoperative biopsy showed that the COF had transformed into an osteosarcoma. The patient subsequently experienced respiratory and cardiac arrests and was receiving treatment in the intensive care unit with a poor prognosis at the time of writing this manuscript. Thus, a high Ki-67 index may be a risk factor for malignant transformation for COFs.