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Pancreatic ductal adenocarcinoma (PDAC) comprises two clinically relevant molecular subtypes that are currently determined using tissue biopsies, which are spatially biased and highly invasive. We used whole transcriptome sequencing of 10 plasma samples with tumor‐informed subtypes, complemented by proteomic analysis for minimally invasive identification of PDAC subtype markers. Data were validated in independent large cohorts and correlated with treatment response and patient outcome. Differential transcript abundance analyses revealed 32 subtype‐specific, protein‐coding cell‐free RNA (cfRNA) transcripts. The subtype specificity of these transcripts was validated in two independent tissue cohorts comprising 195 and 250 cases, respectively. Three disease‐relevant cfRNA‐defined subtype markers (DEGS1, KDELC1, and RPL23AP7) that consistently associated with basal‐like tumors across all cohorts were identified. In both tumor and liquid biopsies, the overexpression of these markers correlated with poor survival. Moreover, elevated levels of the identified markers were linked to a poor response to systemic therapy and early relapse in resected patients. Our data indicate clinical applicability of cfRNA markers in determining tumor subtypes and monitoring disease recurrence. [ABSTRACT FROM AUTHOR]

Aims: To explore the clinical presentations and outcomes among different ages and subtypes of post-operative delirium patients. Design: Systematic review of Published Cases. Methods and data sources: We comprehensively searched PubMed, EMBASE, and MEDLINE for published case reports of post-operative delirium up to April 2023. The systematic review has been registered with PROSPERO. Two researchers independently conducted unblinded reviews of the full-text articles. Results: This study included 116 patients with post-operative delirium. Compared to post-operative delirium patients aged 65 and above, those between 18 and 65 years old have lower rates of a history of hypertension, cardiovascular disease and urinary system disorder comorbidities, as well as higher usage rates of fentanyl analogs and lorazepam. Additionally, these patients exhibit lower incidences of anemia and renal failure, along with a lower mortality rate. Compared to post-operative delirium patients aged 65 and above, those under 18 years old have a higher rate of fentanyl analog usage and a higher incidence of post-operative delirium following neurological surgeries. Among the hypoactive, hyperactive, and mixed subtypes, the reasons for surgery, such as cardiovascular diseases, reproductive system diseases, and neurological disorders, significantly varied among these three subtypes. Furthermore, substance abuse history and medication usage patterns also significantly varied among these three subtypes. Conclusions: Our investigation has revealed noteworthy insights into post-operative delirium in different patient populations. Notably, age emerged as a pivotal factor. Compared to elderly patients (≥65 years), those aged 18 to 65 demonstrate better prognosis. Additionally, patients younger than 18 years with post-operative delirium have a higher incidence of delirium following neurosurgical procedures compared to those elderly patients. Additionally, a strong association was found between a history of substance abuse and hyperactive delirium. Variations in drug use patterns were observed across different subtypes. Importantly, post-operative delirium patients younger than 18 years, as well as those aged 18 to 65 with mixed-subtype delirium, exhibited similar high mortality rates as elderly patients. This underscores the need for increased attention to post-operative delirium patients under 65 and highlights the necessity of rapid identification and early intervention for these populations at risk of poor outcomes. [ABSTRACT FROM AUTHOR]

Simple Summary: Breast cancer is a complex disease with several subtypes that impact different populations in various ways. This study focuses on the diverse ethnic population of Hawai'i. We aim to investigate whether there are differences in breast cancer subtypes among various racial and ethnic groups that could contribute to disparities in breast cancer outcomes. This study analyzes the incidence and prevalence of breast cancer subtypes in these groups, considering factors such as age and tumor biology. By identifying subtype-specific risks and outcomes, we hope to provide insights that could lead to more tailored and effective treatments, thereby improving prognosis and reducing mortality disparities in diverse communities. Our findings have important implications for clinical practice in regions with diverse populations. This study highlights the need for more individualized approaches to breast cancer screening and treatment to improve patient outcomes. Background: Differences in the incidence of breast cancer subtypes among racial/ethnic groups have been evaluated as a contributing factor in disparities seen in breast cancer prognosis. We evaluated new breast cancer cases in Hawai'i to determine if there were subtype differences according to race/ethnicity that may contribute to known disparities. Methods: We reviewed 4591 cases of women diagnosed with breast cancer from two large tumor registries between 2015 and 2022. We evaluated breast cancer cases according to age at diagnosis, self-reported race, breast cancer subtype (ER, PR, and HER2 receptor status), histology, county, and year. Results: We found both premenopausal and postmenopausal Native Hawaiian women were less likely to be diagnosed with triple-negative breast cancer (OR = 0.26, 95% CI 0.12–0.58 p = 0.001; OR = 0.54, 95% CI 0.36, 0.80 p = 0.002, respectively). Conclusions: The results of our study support that there are racial/ethnic differences in breast cancer subtypes among our population, which may contribute to differences in outcomes. Further evaluation of clinical and pathological features in each breast cancer subtype may help improve the understanding of outcome disparities seen among different racial/ethnic groups. [ABSTRACT FROM AUTHOR]

Since Mongolian gerbils are broadly susceptible to hepatitis E virus (HEV), including genotypes 1, 4, 5, and 8 (HEV-1, HEV-5, HEV-5, and HEV-8) and rat HEV, they are a useful small animal model for HEV. However, we have observed that the subtypes HEV-3k and HEV-3ra in genotype 3 HEV (HEV-3) were not infected efficiently in the gerbils. A small-animal model for HEV-3 is also needed since HEV-3 is responsible for major zoonotic HEV infections. To investigate whether gerbils can be used as animal models for other subtypes of HEV-3, we injected gerbils with five HEV-3 subtypes (HEV-3b, -3e, -3f, -3k, and -3ra) and compared the infectivity of the subtypes. We detected viral RNA in the gerbils' feces. High titers of anti-HEV IgG antibodies in serum were induced in all HEV-3b/ch-, HEV-3f-, and HEV-3e-injected gerbils. Especially, the HEV-3e-injected animals released high levels of viruses into their feces for an extended period. The virus replication was limited in the HEV-3b/wb-injected and HEV-3k-injected groups. Although viral RNA was detected in HEV-3ra-injected gerbils, the copy numbers in fecal specimens were low; no antibodies were detected in the sera. These results indicate that although HEV-3′s infectivity in gerbils depends on the subtype and strain, Mongolian gerbils have potential as a small-animal model for HEV-3. A further comparison of HEV-3e with different genotype strains (HEV-4i and HEV-5) and different genera (rat HEV) revealed different ALT elevations among the strains, and liver damage occurred in HEV-4i- and HEV-5-infected but not HEV-3e- or rat HEV-infected gerbils, demonstrating variable pathogenicity across HEVs from different genera and genotypes in Mongolian gerbils. HEV-4i- and HEV-5-infected Mongolian gerbils might be candidate animal models to examine HEV's pathogenicity. [ABSTRACT FROM AUTHOR]

Background: Parkinson's disease (PD) demonstrates considerable heterogeneity in the manifestation of clinical symptoms and disease progression. Recently, six clinical milestones have been proposed to evaluate disease severity in PD. However, the identification of PD progression subtypes based on these milestone events has not yet been performed. Methods: Latent class analysis (LCA) was employed to identify subtypes of PD progression based on the timing of the first occurrence of six milestones within a 6-year follow-up period in Parkinson's Progression Markers Initiative (PPMI) database. Results: The study cohort consisted of 354 early PD patients, of whom 42.9% experienced at least one milestone within six years. LCA identified two distinct subtypes of PD progression: slow progression (83%) and rapid progression (17%). The total number of milestones over six years was significantly higher in the rapid progression subtype compared to the slow progression subtype (median: 3.00 vs. 0.00, p < 0.001). At baseline, the rapid progression subtype, compared to the slow progression subtype, was characterized by an older age at onset and more severe motor and non-motor symptoms. On biomarkers, the rapid progression subtype demonstrated elevated CSF p-tau and serum NFL, but decreased mean striatal DAT uptake. Five clinical variables (age, SDMT score, MDS-UPDRS I score, MDS-UPDRS II + III scores, and RBD) were selected to construct the predictive model. The original predictive model achieved an AUC of 0.82. In internal validation using bootstrap resampling, the model achieved an AUC of 0.82, with a 95%CI ranging from 0.76 to 0.87. The model's performance was acceptable regarding both calibration and clinical utility. Conclusion: Approximately 17% of early PD patients exhibited the rapid progression subtype, characterized by the occurrence of more and earlier-onset milestones. The nomogram predictive model, incorporating five baseline clinical variables (age, SDMT score, MDS-UPDRS I score, MDS-UPDRS II + III scores, RBD), serves as a valuable tool for prognostic counseling and patient selection in PD clinical trials. [ABSTRACT FROM AUTHOR]

The circulating androgens have a role in the pathogenesis of both acne vulgaris and androgenetic alopecia; an association between these two have been found previously. The aim of this study is to investigate the relationship of the severity of acne vulgaris lesions to the subtype of AGA; and to validate the relationship between severities of acne vulgaris and AGA. This study was conducted cross-sectionally at five different dermatology clinics. Male and female androgenetic alopecia patients with comorbid acne vulgaris have been included. The age, gender, severity of acne lesions, subtype of androgenetic alopecia and the severity of androgenetic alopecia were noted. The severity of acne lesions were graded according to the Global Acne Severity Scale and androgenetic alopecia was graded according to the Hamilton and Ludwig Scales. SPSS v 21 was used for the statistical analysis. A total of 101 patients have been included (12 male and 89 female). The mean age of the patients with severe acne was statistically significantly lower (p = 0.020). The difference in terms of gender was statistically insignificant (p = 0.388). The severity of acne vulgaris was found to be independent of the severity and of the subtype of AGA; p = 0.623 and 0.870 respectively. Neither a relationship between the severity of androgenetic alopecia and severity of acne; nor a relationship between acne severity and androgenetic alopecia subtype were found in this study. Thus we report that, acne severity is independent of the subtype and stage of the co-existing androgenetic alopecia. [ABSTRACT FROM AUTHOR]

Objective: We aimed to analyze the effect of high‐intensity focused ultrasound (HIFU) on different types of adenomyosis (AM) based on magnetic resonance imaging (MRI) classification. Methods: A total of 206 AM patients who underwent HIFU between January 2017 and December 2021 were included in this retrospective study. The size and location of AM were evaluated based on T2‐weighted imaging (T2WI) of MRI. Patients were divided into internal (subtype I), external (subtype II), intramural (subtype III), and full‐thickness (subtype IV) AM groups. All patients underwent an MRI examination before and one day after HIFU. After ultrasound‐guided HIFU ablation, the parameters of ultrasonic energy input during HIFU treatment among different groups were recorded and compared. The adverse reactions and complications among different groups were compared. Results: The lesion volume in the subtype IV group was significantly larger than the subtype II and III groups (P <.05). The HIFU irradiation time, treatment time, and total energy input in the subtype IV group were significantly higher than the subtype I and III groups (P <.05). The number of cases of abdominal pain and vaginal fluid in the treatment area in the subtype IV group was significantly higher than in the subtype II group. Conclusion: Although HIFU has different treatment strategies and parameters for different subtypes of AM, it can achieve a satisfactory ablation rate, which is safe and effective. [ABSTRACT FROM AUTHOR]

The presence of pretreatment drug resistance (PDR) is posing an increasing threat to HIV control. Here we investigated drug resistance mutations (DRMs) and PDR among 6831 HIV‐infected individuals from 2018 to 2022 in Guangzhou, China. DRMs were detected among 24.5% of the patients. The overall prevalence of PDR was 7.4%, with resistance rate to nucleotide reverse transcriptase inhibitor (NRTI) being 1.3%, nonnucleoside reverse transcriptase inhibitor (NNRTI) 4.8%, and protease inhibitor (PI) 1.4%. Abacavir (0.8%) resistance was the most common in NRTI, followed by resistance to emtricitabine (0.6%), lamivudine (0.6%), and tenofovir disoproxil fumarate (0.3%). In NNRTI, nevirapine (3.7%) resistance was the most common, followed by efavirenz (3.5%) and rilpivirine (3.4%). Among PI, resistance to tipranavir (0.8%), nelfinavir (0.6%), fosamprenavir (0.2%) and lopinavir (0.1%) was most frequent. Annual prevalence of PDR showed an increase trend from 2018 to 2022, although not significant. In the multivariable logistic regression model, hepatitis B surface antigen positivity, circulating recombinant form (CRF) 55_01B, CRF08_BC, CRF59_01B, and subtype B were demonstrated as associated risk factors for PDR. The overall prevalence of PDR in Guangzhou was moderate, with relatively severe NNRTI resistance. Therefore, it remains crucial to continue monitoring PDR among newly diagnosed HIV‐infected individuals. [ABSTRACT FROM AUTHOR]

Exposure to toxic heavy metals has been associated with the development of attention-deficit/hyperactivity disorder (ADHD). However, fewer studies have examined the associations between abnormal levels of essential trace metals and ADHD, and none have done so using saliva. We investigated whether salivary metals were associated with ADHD in adolescents aged 12 from the Family Life Project (FLP) using a nested case–control study design that included 110 adolescents who met diagnostic criteria for inattentive (ADHD-I), hyperactive-impulsive (ADHD-H), or combined type ADHD (ADHD-C) (cases) and 173 children who did not (controls). We used inductively coupled plasma optical emission spectrophotometry to measure chromium, copper, manganese, and zinc in saliva samples. We employed logistic regression models to examine associations between quartile levels of individual metals and ADHD outcomes by subtype. Salivary copper levels were significantly associated with increased odds of any ADHD diagnosis (OR = 3.31, 95% CI: 1.08–10.12; p = 0.04) and with increased odds of ADHD-C diagnosis (OR = 8.44, 95% CI: 1.58–45.12; p = 0.01). Salivary zinc levels were significantly associated with increased odds of ADHD-C diagnosis (OR = 4.06, 95% CI: 1.21–13.69; p = 0.02). Salivary manganese levels were also significantly associated with increased odds of ADHD-C diagnosis (OR = 5.43, 95% CI: 1.08–27.27, p = 0.04). This is the first study using saliva to assess metal exposure and provide a potential link between salivary levels of copper, manganese, and zinc and ADHD diagnoses in adolescents. Public health interventions focused on metal exposures might reduce ADHD incidence in low-income, minority communities. [ABSTRACT FROM AUTHOR]

Objective: Pediatric athletes with concussion present with a variety of impairments on clinical assessment and require individualized treatment. The Buffalo Concussion Physical Examination is a brief, pertinent clinical assessment for individuals with concussion. The purpose of this study was to identify physical examination subtypes in pediatric athletes with concussion within 2 weeks of injury that are relevant to diagnosis and treatment. Design: Secondary analysis of a published cohort study and clinician consensus. Setting: Three university-affiliated sports medicine centers. Participants: Two hundred seventy children (14.961.9 years). Independent Variables: Orthostatic intolerance, horizontal and vertical saccades, smooth pursuits, vestibulo-ocular reflex, near-point convergence, complex tandemgait, neck range of motion, neck tenderness, and neck spasm. Main Outcome Measures: Correlations between independent variables were calculated, and network graphs were made. k-means and hierarchical clustering were used to identify clusters of impairments. Optimal number of clusters was assessed. Results were reviewed by experienced clinicians and consensus was reached on proposed subtypes. Results: Physical examination clusters overlapped with each other, and no optimal number of clusters was identified. Clinician consensus suggested 3 possible subtypes: (1) visio-vestibular (horizontal and vertical saccades, smooth pursuits, and vestibulo-ocular reflex), (2) cervicogenic (neck range of motion and spasm), and (3) autonomic/balance (orthostatic intolerance and complex tandemgait). Conclusions: Although we identified 3 physical examination subtypes, it seemed that physical examination findings alone are not enough to define subtypes that are both statistically supported and clinically relevant, likely because they do not include symptoms, assessment of mood or cognitive problems, or graded exertion testing. [ABSTRACT FROM AUTHOR]

Autism is heterogeneous, which complicates providing tailored support and future prospects. We aim to identify subgroups in autistic adults with average to high intelligence, to clarify if certain subgroups might need support. We included 14 questionnaire variables related to aging and/or autism (e.g., demographic, psychological, and lifestyle). Community detection analysis was used for subgroup identification in an original sample of 114 autistic adults with an adulthood diagnosis (autism) and 58 non-autistic adults as comparison group (COMP), and a replication sample (NAutism = 261; NCOMP = 287), both aged 30–89 years. Next, we identified subgroups and assessed external validity (for cognitive and psychological difficulties, and quality of life [QoL]) in the autism samples. To test specificity, we repeated the analysis after adding 123 adults with ADHD, aged 30–80 years. As expected, the autism and COMP groups formed distinct subgroups. Among autistic adults, we identified three subgroups of which two were replicated. One of these subgroups seemed most vulnerable on the cluster variables; this subgroup also reported the most cognitive and psychological difficulties, and lowest QoL. Adding the ADHD group did not alter results. Within autistic adults, one subgroup could especially benefit from support and specialized care, although this must be tested in future studies. [ABSTRACT FROM AUTHOR]

Introduction: Breast cancer subtyping is used clinically for diagnosis, prognosis, and treatment decisions. Subtypes are categorized by cell of origin, histomorphology, gene expression signatures, hormone receptor status, and/or protein levels. Categorizing breast cancer based on gene expression signatures aids in assessing a patient's recurrence risk. Protein biomarkers, on the other hand, provide functional data for selecting therapies for primary and recurrent tumors. We provide an update on protein biomarkers in breast cancer subtypes and their application in prognosis and therapy selection. Areas covered: Protein pathways in breast cancer subtypes are reviewed in the context of current protein-targeted treatment options. PubMed, Science Direct, Scopus, and Cochrane Library were searched for relevant studies between 2017 and 17 August 2024. Expert opinion: Post-translationally modified proteins and their unmodified counterparts have become clinically useful biomarkers for defining breast cancer subtypes from a therapy perspective. Tissue heterogeneity influences treatment outcomes and disease recurrence. Spatial profiling has revealed complex cellular subpopulations within the breast tumor microenvironment. Deciphering the functional relationships between and within tumor clonal cell populations will further aid in defining breast cancer subtypes and create new treatment paradigms for recurrent, drug resistant, and metastatic disease. [ABSTRACT FROM AUTHOR]

Background: Meningioma subtype is crucial in treatment planning and prognosis delineation, for grade 1 meningiomas. T2 relaxometry could provide detailed microscopic information but is often limited by long scanning times. Purpose: To investigate the potential of T2 maps derived from multiple overlapping‐echo detachment imaging (MOLED) for predicting meningioma subtypes and Ki‐67 index, and to compare the diagnostic efficiency of two different region‐of‐interest (ROI) placements (whole‐tumor and contrast‐enhanced, respectively). Study Type: Prospective. Phantom/Subjects: A phantom containing 11 tubes of MnCl2 at different concentrations, eight healthy volunteers, and 75 patients with grade 1 meningioma. Field Strength/Sequence: 3 T scanner. MOLED, T2‐weighted spin‐echo sequence, T2‐dark‐fluid sequence, and postcontrast T1‐weighted gradient echo sequence. Assessment: Two ROIs were delineated: the whole‐tumor area (ROI1) and contrast‐enhanced area (ROI2). Histogram parameters were extracted from T2 maps. Meningioma subtypes and Ki‐67 index were reviewed by a neuropathologist according to the 2021 classification criteria. Statistical Tests: Linear regression, Bland–Altman analysis, Pearson's correlation analysis, independent t test, Mann–Whitney U test, Kruskal–Wallis test with Bonferroni correction, and multivariate logistic regression analysis with the P‐value significance level of 0.05. Results: The MOLED T2 sequence demonstrated excellent accuracy for phantoms and volunteers (Meandiff = −1.29%, SDdiff = 1.25% and Meandiff = 0.36%, SDdiff = 2.70%, respectively), and good repeatability for volunteers (average coefficient of variance = 1.13%; intraclass correlation coefficient = 0.877). For both ROI1 and ROI2, T2 variance had the highest area under the curves (area under the ROC curve = 0.768 and 0.761, respectively) for meningioma subtyping. There was no significant difference between the two ROIs (P = 0.875). Significant correlations were observed between T2 parameters and Ki‐67 index (r = 0.237–0.374). Data Conclusion: MOLED T2 maps can effectively differentiate between meningothelial, fibrous, and transitional meningiomas. Moreover, T2 histogram parameters were significantly correlated with the Ki‐67 index. Level of Evidence: 1 Technical Efficacy: Stage 2 [ABSTRACT FROM AUTHOR]

We present the clinicopathological features of 23 cases of the giant cell subtype of urothelial carcinoma, a rare subtype of bladder cancer recognized in the current World Health Organization classification of urological tumors. Histologically, the architectural pattern of the tumor varied from infiltrating to the solid expansile pleomorphic tumor with giant, bizarre, anaplastic cells. Typical or atypical mitotic figures were frequently present in all cases. Between 10 and 30% of the tumor had a giant cell component. All cases were associated with conventional high-grade urothelial carcinoma, with areas of squamous cell divergent differentiation and micropapillary carcinoma present in six and two cases, respectively. In one case each had sarcomatoid, nested, small cell, or glandular divergent differentiation. At diagnosis, 35% of patients had advanced disease and 12% had distant metastases. When comparing giant cell urothelial carcinoma with conventional urothelial carcinoma in a matched analysis, differences in overall and cancer-specific survival were observed, particularly in the T1 stage category. Immunohistochemical staining showed a similar profile of urothelial lineage with frequent positive expression of uroplakin II, GATA3, CK20, CK7, and S100P in both giant cell and conventional urothelial carcinomas. High Ki67 proliferation (range, 60–90%; mean, 71%) and nuclear p53 accumulation (mutant profile; range, 50–90%; mean, 64%) were observed. Using the 22C3 assay, the expression of PD-L1 was found to be variable in two cases, and beta-HCG was negative. In conclusion, giant cell carcinoma is a subtype of urothelial carcinoma associated with advanced clinical stage and a trend to lower survival rates. [ABSTRACT FROM AUTHOR]

Abstract Background There is a substantial body of observational research indicating an association between hearing impairment and dementia, yet the causal relationship and underlying mechanisms remain uncertain. This study aims to investigate the causal relationship between hearing impairment and its subtypes with dementia and cognitive function using two-sample Mendelian randomization (MR) analysis. Methods We performed two-sample MR analysis to examine the causal effects of hearing impairment and its subtypes, including conductive and sensorineural hearing loss (CSHL), conductive hearing loss (CHL), sensorineural hearing loss (SHL), and sudden sensorineural hearing loss (SIHL), on six dementia phenotypes (overall dementia, Alzheimer’s disease [AD], Lewy body dementia [DLB], frontotemporal dementia [FTD], Parkinson’s disease dementia, and vascular dementia) and four cognitive functions. Additionally, multivariable MR (MVMR) analysis was employed to investigate potential mediating mechanisms. Results Genetically determined CSHL was associated with an elevated risk of DLB (odds ratio [OR] 1.69; 95% CI 1.08 to 2.63; P = 0.021) and FTD (OR 1.66; 1.04 to 2.67; P = 0.035), but not AD (P = 0.958). Genetic predisposition to CHL was found to link with increased risks of AD (OR 1.07; 1.01 to 1.14; P = 0.031). Genetically determined SHL was causally associated with an elevated risk of semantic dementia (OR 3.81; 1.09 to 13.37; P = 0.037). Genetically predicted CHL and SIHL were both causally associated with lower general cognitive performance (β -0.015 and − 0.043; P = 0.007 and 0.013) and fluid intelligence score (β -0.045 and − 0.095; P = 0.037 and 0.040). In MVMR analysis, the causal relationship between hearing impairment and dementia was mediated by loneliness, depressed mood, and brain cortical volume, particularly the medial temporal lobe, but not by aging or ischemic stroke. Conclusion Overall, the study provides evidence supporting a causal relationship between hearing impairment and increased risks of different types of dementia (including AD, FTD, and DLB), as well as poorer general cognitive function. These findings underscore the importance of addressing hearing impairment as a modifiable risk factor for dementia.

We isolated highly pathogenic avian influenza (HPAI) H5N5 and H5N1 viruses from crows in Hokkaido, Japan, during winter 2023–24. They shared genetic similarity with HPAI H5N5 viruses from northern Europe but differed from those in Asia. Continuous monitoring and rapid information sharing between countries are needed to prevent HPAI virus transmission.

Dysregulation of adenosine-to-inosine (A-to-I) RNA editing has been implicated in cancer progression. However, a comprehensive understanding of how A-to-I RNA editing is incorporated into miRNA regulation to modulate gene expression in cancer remains unclear, given the lack of effective identification methods. To this end, we introduced an information theory-based algorithm named REMR to systematically identify 12,006 A-to-I RNA editing-mediated miRNA regulatory triplets (RNA editing sites, miRNAs, and genes) across ten major cancer types based on multi-omics profiling data from The Cancer Genome Atlas (TCGA). Through analyses of functional enrichment, transcriptional regulatory networks, and protein-protein interaction (PPI) networks, we showed that RNA editing-mediated miRNA regulation potentially affects critical cancer-related functions, such as apoptosis, cell cycle, drug resistance, and immunity. Furthermore, triplets can serve as biomarkers for classifying cancer subtypes with distinct prognoses or drug responses, highlighting the clinical relevance of such regulation. In addition, an online resource (http://www.jianglab.cn/REMR/) was constructed to support the convenient retrieval of our findings. In summary, our study systematically dissected the RNA editing-mediated miRNA regulations, thereby providing a valuable resource for understanding the mechanism of RNA editing as an epitranscriptomic regulator in cancer.

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma (NHL) and is characterized by high heterogeneity. Assessment of its prognosis and genetic subtyping hold significant clinical implications. However, existing DLBCL prognostic models are mainly based on transcriptomic profiles, while genetic variation detection is more commonly used in clinical practice. In addition, current clustering-based subtyping methods mostly focus on genes with high mutation frequencies, providing insufficient explanations for the heterogeneity of DLBCL. Here, we proposed VNNSurv (https://bio-web1.nscc-gz.cn/app/VNNSurv), a survival model for DLBCL patients based on a biologically informed visible neural network (VNN). VNNSurv achieved an average C-index of 0.72 on the cross-validation set (HMRN cohort, n = 928), outperforming the baseline methods. The remarkable interpretability of VNNSurv facilitated the identification of the most impactful genes and the underlying pathways through which they act on patient outcomes. When only the 30 highest-impact genes were used as genetic input, the overall performance of VNNSurv improved, and a C-index of 0.70 was achieved on the external TCGA cohort (n = 48). Leveraging these high-impact genes, including 16 genes with low (

The aim of this study is to establish a deep learning (DL) model to predict the pathological type of gastric adenocarcinoma cancer based on whole-slide images(WSIs). We downloaded 356 histopathological images of gastric adenocarcinoma (STAD) patients from The Cancer Genome Atlas database and randomly divided them into the training set, validation set and test set (8:1:1). Additionally, 80 H&E-stained WSIs of STAD were collected for external validation. The CLAM tool was used to cut the WSIs and further construct the model by DL algorithm, achieving an accuracy of over 90% in identifying and predicting histopathological subtypes. External validation results demonstrated the model had a certain generalization ability. Moreover, DL features were extracted from the model to further investigate the differences in immune infiltration and patient prognosis between the two subtypes. The DL model can accurately predict the pathological classification of STAD patients, and provide certain reference value for clinical diagnosis. The nomogram combining DL-signature, gene-signature and clinical features can be used as a prognostic classifier for clinical decision-making and treatment. [ABSTRACT FROM AUTHOR]

To determine if subtypes of cam morphology on anteroposterior radiographs exist using statistical shape modeling (SSM), and to assess their association with incident radiographic hip osteoarthritis (RHOA) within 10 years. The nationwide prospective Cohort Hip and Cohort Knee (CHECK) study included 1002 participants aged 45–65 years with 10-year follow-up. Subtypes of cam morphology were defined as SSM-based shape variations of femoral head-neck junction that are associated with baseline cam morphology (alpha angle ≥60°). The association between each subtype in hips free of osteoarthritis at baseline (Kellgren & Lawrence (KL) grade <2) and incident RHOA (KL grade≥2, or a total hip replacement) was estimated using logistic regression at 10-year follow-up and stratified by sex. In sex-combined group, but also for males and females separately, cam morphology subtypes were captured in modes 1, 3, 4, and 5 with odds ratios (ORs) ranging from 0.39 (0.27–0.58) to 2.25 (1.64–3.10). For sex-combined group, only mode 3, a flattened head-neck junction, was associated with incident RHOA (OR:1.14, 1.02–1.27). Males' modes 1 and 3 and females' modes 3 and 4 were associated with RHOA. Notably, the female mode 4, a slightly flattened neck but with subtle curvature, was significantly protective for RHOA (OR:0.88, 0.80–0.98). We identified four distinct morphological subtypes of cam morphology defined by alpha angle. Only some subtypes were found acting as risk factors for RHOA at 10-year follow-up, which differed between males and females. This highlights the need to study cam morphology beyond the alpha angle alone. [ABSTRACT FROM AUTHOR]

Abstract Background The number and proportion of HIV/AIDS patients among older people are continuously and rapidly increasing in China. We conducted a detailed molecular epidemiological analysis of HIV-1 epidemic strains in a developed city in eastern China and found that elderly people play a crucial role in the transmission of subtypes and high pretreatment drug resistance (PDR). Methods A total of 1048 samples were obtained from 1129 (92.8%) newly confirmed HIV-1-positive and treatment-naive patients between 2019 and 2023. The 1316 bp target fragment of the pol gene was amplified by reverse transcription polymerase chain reaction (RT‒PCR) and nested PCR, and Maximum-likelihood (ML) phylogenetic trees and molecular transmission network were constructed to analyse the subtypes and transmission clusters. Molecular transmission network was visualized using Cytoscape with the distance threshold of 0.0075. PDR-associated mutations were determined according to the Stanford University HIV Drug Resistance Database. Results A total of 933 pol sequences (89.0%, 933/1048) were successfully obtained, and twelve HIV-1 subtypes were detected. CRF07_BC was the predominant subtype, accounting for 48.1% (449/933) of sequences, followed by CRF01_AE (29.4%, 274/933). A total of 398 individuals (42.7%, 398/933) formed 89 clusters in the network. Multivariable logistic regression analysis revealed that age, nationality, subtype, and PDR were the most significant factors associated with clustering in the transmission network. The prevalence of PDR was 14.6% (136/933).PDR associated with non-nucleoside reverse transcriptase inhibitors (10.0%, 93/933) was much more common than that associated with nucleoside reverse transcriptase inhibitors (1.8%, 17/933) and protease inhibitors (3.2%, 30/933) (χ 2 = 77.961, p

Purpose: The present study aimed to analyze and compare sonographic features of papillary thyroid carcinoma (PTC) subtypes to determine whether ultrasound (US) may aid in differentiating particular subtypes. Methods: This retrospective study enrolled 133 patients diagnosed with 142 histopathologically proven PTCs as per the fifth edition of the World Health Organization classification of thyroid neoplasms between January 2013 and May 2023. US features based on the American College of Radiology and European Thyroid Imaging and Reporting Data Systems (TIRADS), and histopathological characteristics of nodules were assessed and compared. Results: Histopathological analysis yielded 55 (38.7%) classic PTC, 32 (22.5%) invasive encapsulated follicular variant (IEFV) PTC, 20 (14.1%) oncocytic subtype, 14 (9.9%) non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), 11 (7.8%) infiltrative follicular subtype, 7 (4.9%) tall cell subtype, 2 (1.4%) solid subtype, and 1 (0.7%) diffuse sclerosing subtype. The US findings indicating malignancy, such as taller-than-wide shape, irregular margins, echogenic foci, and higher TIRADS categories, were more frequently demonstrated in nodules with classic PTC and the tall cell subtype, in line with their histopathological features. Conversely, IEFV-PTC and NIFTP rarely exhibited these high-risk sonographic features. US appearance of the oncocytic subtype more frequently overlapped with IEFV-PTC, yet hypo/very hypoechoic nodules with larger nodular diameters and higher TIRADS scores may favor the diagnosis of this subtype. Conclusion: US features of certain subtypes may guide the differential diagnosis regarding shape, margin, echogenic foci, and TIRADS category of nodules; however, definitive subtyping is not yet possible using US images alone. [ABSTRACT FROM AUTHOR]

Background: The number and proportion of HIV/AIDS patients among older people are continuously and rapidly increasing in China. We conducted a detailed molecular epidemiological analysis of HIV-1 epidemic strains in a developed city in eastern China and found that elderly people play a crucial role in the transmission of subtypes and high pretreatment drug resistance (PDR). Methods: A total of 1048 samples were obtained from 1129 (92.8%) newly confirmed HIV-1-positive and treatment-naive patients between 2019 and 2023. The 1316 bp target fragment of the pol gene was amplified by reverse transcription polymerase chain reaction (RT‒PCR) and nested PCR, and Maximum-likelihood (ML) phylogenetic trees and molecular transmission network were constructed to analyse the subtypes and transmission clusters. Molecular transmission network was visualized using Cytoscape with the distance threshold of 0.0075. PDR-associated mutations were determined according to the Stanford University HIV Drug Resistance Database. Results: A total of 933 pol sequences (89.0%, 933/1048) were successfully obtained, and twelve HIV-1 subtypes were detected. CRF07_BC was the predominant subtype, accounting for 48.1% (449/933) of sequences, followed by CRF01_AE (29.4%, 274/933). A total of 398 individuals (42.7%, 398/933) formed 89 clusters in the network. Multivariable logistic regression analysis revealed that age, nationality, subtype, and PDR were the most significant factors associated with clustering in the transmission network. The prevalence of PDR was 14.6% (136/933).PDR associated with non-nucleoside reverse transcriptase inhibitors (10.0%, 93/933) was much more common than that associated with nucleoside reverse transcriptase inhibitors (1.8%, 17/933) and protease inhibitors (3.2%, 30/933) (χ2 = 77.961, p < 0.001). The most frequent NNRTI mutations were K103N/S/KN/NS (52.2%, 71/136), which led to the highest proportion of high-level resistance to nevirapine and efavirenz (52.2%). Conclusions: Our study revealed the important influence of elderly people on CRF07_BC transmission and the high prevalence of PDR. The clustering of drug-resistant cases was significant, which suggested the potential for localized widespread transmission of drug-resistant strains. HIV screening and the determination of PDR are recommended for older patients to improve early detection and reduce treatment failure and second-generation transmission. [ABSTRACT FROM AUTHOR]

Introduction: Homosexual transmission has contributed greatly to the current HIV-1 epidemic in Hebei province, China. Dolutegravir (DTG) will be conditionally used as a component of free antiretroviral therapy (ART) according to manual for national free anti-AIDS treatment drugs (2023 edition) issued by China in June 2023. However, current genetic characteristics and pretreatment drug resistance (PDR) to proteinase inhibitors (PIs), reverse transcriptase inhibitors (RTs) and integrase strand transfer inhibitors (INSTIs) of HIV-1 in this population have remained unclear. Methods: Serial consecutive cross-sectional analyses for HIV- 1 infection trend, genetic characteristics, PDR and molecular transmission networks were conducted from 2018 to 2022. All of participants were HIV-1- infected MSM newly diagnosed at the HIV surveillance points (HSPs) in Hebei, China. Evidence of PDR was confirmed using the world health organization (WHO) list for surveillance of drug resistance mutations. Results: In this study, a total of 14 HIV-1 subtypes were circulating in the HSPs of Hebei province, China. CRF01_ AE (51.9%, 350/675), CRF07_BC (30.4%, 205/675), B (6.2%, 42/675) and URFs (5.8%, 39/675) were the four most predominant subtypes among MSM. And, CRF07_BC (r > 0) and URFs (r > 0) indicated an increasing trend, respectively; however, CRF01_AE (r < 0) showed a decline trend. The overall prevalence of HIV-1 PDR showed a substantial increase from 6.3% in 2018 to 7.9% in 2022. The prevalence of NNRTI-PDR was the highest (5.8%, 39/675), followed by INSTIs (2.4%, 16/675), NRTIs (0.6%, 4/675) and PIs (0.3%, 2/675). Furthermore, extensive HIV-1 strains bearing PDR were circulating in the MSM population via molecular transmission networks for major HIV-1 subtypes, especially CRF01_AE and CRF07_BC. Discussion: Our findings reflect that HIV-1 epidemic in the MSM population is complex and severe in Hebei, China. Therefore, it is urgent for us to implement more effective intervention measures to limit the further dissemination of HIV-1, especially the spread of HIV-1 INSTI-PDR strains. [ABSTRACT FROM AUTHOR]

Objective: To analyse the impact of histological discordance of subtypes (subtypes or divergent differentiation [DD]) in specimens from transurethral resection (TUR) and radical cystectomy (RC) on the outcome of the patients with bladder cancer receiving RC. Patients and methods: We analysed data for 2570 patients from a Japanese nationwide cohort with bladder cancer treated with RC between January 2013 and December 2019 at 36 institutions. The non‐urinary tract recurrence‐free survival (NUTR‐FS) and overall survival (OS) stratified by TUR or RC specimen histology were determined. We also elucidated the predictive factors for OS in patients with subtype/DD bladder cancer. Results: At median follow‐up of 36.9 months, 835 (32.4%) patients had NUTR, and 691 (26.9%) died. No statistically significant disparities in OS or NUTR‐FS were observed when TUR specimens were classified as pure‐urothelial carcinoma (UC), subtypes, DD, or non‐UC. Among 2449 patients diagnosed with pure‐UC or subtype/DD in their TUR specimens, there was discordance between the pathological diagnosis in TUR and RC specimens. Histological subtypes in RC specimens had a significant prognostic impact. When we focused on 345 patients with subtype/DD in TUR specimens, a multivariate Cox regression analysis identified pre‐RC neutrophil–lymphocyte ratio and pathological stage as independent prognostic factors for OS (P = 0.016 and P = 0.001, respectively). The presence of sarcomatoid subtype in TUR specimens and lymphovascular invasion in RC specimens had a marginal effect (P = 0.069 and P = 0.056, respectively). Conclusion: This study demonstrated that the presence of subtype/DD in RC specimens but not in TUR specimens indicated a poor prognosis. In patients with subtype/DD in TUR specimens, pre‐RC neutrophil–lymphocyte ratio and pathological stage were independent prognostic factors for OS. [ABSTRACT FROM AUTHOR]

Background: Increased glycolytic activity and lactate production are characteristic features of triple‐negative breast cancer (TNBC). The aim of this study was to determine whether a subset of lactate‐responsive genes (LRGs) could be used to classify TNBC subtypes and predict patient outcomes. Methods: Lactate levels were initially measured in different breast cancer (BC) cell types. Subsequently, MDA‐MB‐231 cells treated with 2‐Deoxy‐d‐glucose or l‐lactate were subjected to RNA sequencing (RNA‐seq). The gene set variation analysis algorithm was utilized to calculate the lactate‐responsive score, conduct a differential analysis, and establish an association with the extent of immune infiltration. Consensus clustering was then employed to classify TNBC patients. Tumor immune dysfunction and exclusion, cibersort, single‐sample gene set enrichment analysis, and EPIC, were used to compare the tumor‐infiltrating immune cells between TNBC subtypes and predict the response to immunotherapy. Furthermore, a prognostic model was developed by combining 98 machine learning algorithms, to assess the predictive significance of the LRG signature. The predictive value of immune infiltration and the immunotherapy response was also assessed. Finally, the association between lactate and various anticancer drugs was examined based on expression profile similarity principles. Results: We found that the lactate levels of TNBC cells were significantly higher than those of other BC cell lines. Through RNA‐seq, we identified 14 differentially expressed LRGs in TNBC cells under varying lactate levels. Notably, this LRG signature was associated with interleukin‐17 signaling pathway dysregulation, suggesting a link between lactate metabolism and immune impairment. Furthermore, the LRG signature was used to categorize TNBC into two distinct subtypes, whereby Subtype A was characterized by immunosuppression, whereas Subtype B was characterized by immune activation. Conclusion: We identified an LRG signature in TNBC, which could be used to predict the prognosis of patients with TNBC and gauge their response to immunotherapy. Our findings may help guide the precision treatment of patients with TNBC. [ABSTRACT FROM AUTHOR]

Using a comprehensive molecular epidemiological approach, we characterized the transmission dynamics of HIV‐1 among the MSM population in Tianjin, China. Our findings revealed that 38.56% (386/1001) of individuals clustered across 109 molecular transmission clusters (TCs), with MSM aged 50 and below being the group most commonly transmitting HIV‐1. Among the identified TCs, CRF01_AE predominated, followed by CRF07_BC. Notably, CRF07_BC demonstrated a higher propensity for forming large clusters compared to CRF01_AE. Birth‐death skyline analyses of the two largest clusters indicated that the HIV/AIDS transmission may be at a critical point, nearly all had Re approximately 1 by now. A retrospective analysis revealed that the rapid expansion of these large clusters was primarily driven by the introduction of viruses in 2021, highlighting the crucial importance of continuous molecular surveillance in identifying newly emerging high‐risk transmission chains and adapting measures to address evolving epidemic dynamics. Furthermore, we detected the transmission of drug‐resistant mutations (DRMs) within the TCs, particularly in the CRF07_BC clusters (K103N, Y181C, and K101E) and CRF01_AE clusters (P225H and K219R), emphasizing the importance of monitoring to support the continued efficacy of first‐line therapies and pre‐exposure prophylaxis (PrEP). Recombination analyses indicated that complex recombinant patterns, associated with increased amino acid variability, could confer adaptive traits to the viruses, potentially providing a competitive advantage in certain host populations or regions. Our study highlights the potential of integrating molecular epidemiological and phylodynamic approaches to inform targeted interventions. [ABSTRACT FROM AUTHOR]

Introduction: Blastocystis is one of the most critical intestinal protozoans in various hosts, including humans and mice. To determine the status of Blastocystis infection in wild rodents in China. Methods: A total of 344 faecal samples were collected from seven wild rodent species from three provinces, and the small subunit ribosomal RNA (SSU rRNA) genes of Blastocystis were amplified to determine their prevalence and subtypes. Results: Of the 344 samples, 54 (15.70%) were detected as Blastocystis-positive. The prevalence of Blastocystis was 26.14% (40/153), 7.95% (7/88), and 6.80% (7/103) in wild rodents from Hunan Province, Yunnan Province, and Guangxi Province, respectively. The prevalence of Blastocystis in different wild rodent species varied from 0.00% (0/13) in Mus musculus to 40.00% (2/5) in Rattus rattus sladeni. The prevalence of Blastocystis in samples from the lake beach area (27.40%, 40/146) was significantly higher than in those from the mountain (6.80%, 7/103) and field regions (7.37%, 7/95). The prevalence in different seasons was 26.14% in summer (40/153), 7.95% in autumn (7/88), and 6.80% in winter (7/103). Moreover, a total of two Blastocystis subtypes were identified in the investigated wild rodents, including ST4 and ST5. Discussion: The present study discovered the existence of Blastocystis infection in Rattus favipectus, Microtus fortis, Apodemus agrarius, Bandicota indica, Rattus rattus sladeni, and Rattus losea, expanding the host range of this parasite. The findings also demonstrate that wild rodents may be an important potential infection source for Blastocystis infection in humans and other animals. [ABSTRACT FROM AUTHOR]

Background Epigenetic changes are plausible molecular sources of clinical heterogeneity in schizophrenia. A subgroup of schizophrenia patients with elevated inflammatory or immune-dysregulation has been reported by previous studies. However, little is known about epigenetic changes in genes related to immune activation in never-treated first-episode patients with schizophrenia (FES) and its consistency with that in treated long-term ill (LTS) patients. Methods In this study, epigenome-wide profiling with a DNA methylation array was applied using blood samples of both FES and LTS patients, as well as their corresponding healthy controls. Non-negative matrix factorization (NMF) and k -means clustering were performed to parse heterogeneity of schizophrenia, and the consistency of subtyping results from two cohorts. was tested. Results This study identified a subtype of patients in FES participants (47.5%) that exhibited widespread methylation level alterations of genes enriched in immune cell activity and a significantly higher proportion of neutrophils. This clustering of FES patients was validated in LTS patients, with high correspondence in epigenetic and clinical features across two cohorts Conclusions In summary, this study demonstrated a subtype of schizophrenia patients across both FES and LTS cohorts, defined by widespread alterations in methylation profile of genes related to immune function and distinguishing clinical features. This finding illustrates the promise of novel treatment strategies targeting immune dysregulation for a subpopulation of schizophrenia patients. [ABSTRACT FROM AUTHOR]

The high proportion of AIDS cases and mortality rates in Guangxi underscores the urgency to investigate the influence of HIV-1 genetic diversity on disease progression in this region. Newly diagnosed HIV-1 patients were enrolled from January 2016 to December 2021, and the follow-up work and detection of CD4+T lymphocytes were carried out every six months until December 2022. Multivariate logistic regression was used to analyze the factors affecting pre-treatment CD4+T lymphocyte counts, while local weighted regression models (LOESS) and generalized estimating equation models (GEE) were conducted to assess factors influencing CD4+T Lymphocyte Recovery. Cox regression analysis was utilized to examine the impact of subtypes on survival risk. Additionally, HIV- 1 env sequences were utilized for predicting CXCR4 and CCR5 receptors. The study encompassed 1867 individuals with pol sequences and 281 with env sequences. Our findings indicate that age over 30, divorced/widowed, peasant, heterosexual infection, CRF01_AE, long-term infection, and Pre-treatment Viral load >10000 copies/ml were factors associated with higher risk for pretreatment CD4+T lymphocyte decline. Specifically, male gender, age over 30, heterosexual infection (HETs), long-term infection, CRF01_AE, and Pretreatment CD4 T cell counts below 350/µL were identified as risk factors impeding CD4+T lymphocyte recovery. Pre-treatment CD4+T lymphocyte counts and recovery in individuals infected with CRF01_AE were lower compared to CRF07_BC and CRF55_01B. Additionally, CRF01_AE and CRF08_BC subtypes exhibited higher mortality rates than CRF07_BC, CRF55_01B, and other subtypes. Notably, CRF01_AE demonstrated the highest percentage of CXCR4 affinity ratios. This research unveils the intricate influence of HIV-1 gene diversity on CD4+T lymphocyte dynamics and clinical outcomes. It highlights the multifaceted nature of HIV infection in Guangxi, providing novel insights into subtype-specific disease progression among HIV-infected individuals in this region. [ABSTRACT FROM AUTHOR]

The HIV-1 pandemic, spanning four decades, presents a significant challenge to global public health. This study aimed to understand the molecular transmission characteristics of newly reported HIV infections in Taiyuan, Shanxi Province, China, to analyze the characteristics of subtypes and the risk factors of the transmission network, providing a scientific basis for precise prevention and intervention measures. A total of 720 samples were collected from newly diagnosed HIV-1 patients residing in Taiyuan between 2021 and 2023. Sequencing of partial genes of the HIV-1 pol gene resulted in multiple sequence acquisitions and was conducted to analyze their subtypes and molecular transmission networks. Out of the samples, 584 pol sequences were obtained, revealing 17 HIV-1 subtypes, with CRF07_BC (48.29%), CRF01_AE (31.34%), and CRF79_0107 (7.19%) being the dominant subtypes. Using a genetic distance threshold of 1.5%, 49 molecular transmission clusters were generated from the 313 pol gene sequences. Univariate analysis showed significant differences in the HIV transmission molecular network in terms of HIV subtype and household registration (p < 0.05). Multivariate logistic regression analysis showed that CRF79_0107 subtype and its migrants were associated with higher proportions of sequences in the HIV transmission network. These findings provide a scientific foundation for the development of localized HIV-specific intervention strategies. [ABSTRACT FROM AUTHOR]

Objective: Frontal hypometabolism on FDG-PET is observed in progressive supranuclear palsy (PSP), although it is unclear whether it is a feature of all PSP clinical variants and hence whether it is a useful diagnostic feature. We aimed to compare the frequency, severity, and pattern of frontal hypometabolism across PSP variants and determine whether frontal hypometabolism is related to clinical dysfunction. Methods: Frontal hypometabolism in prefrontal, premotor, and sensorimotor cortices was visually graded on a 0–3 scale using CortexID Z-score images in 137 PSP patients. Frontal asymmetry was recorded. Severity scores were used to categorize patients as premotor-predominant, prefrontal-predominant, sensorimotor-predominant, mixed-predominance, or no regional predominance. Frontal ratings were compared across PSP clinical variants, and Spearman correlations were used to assess relationships with the Frontal Assessment Battery (FAB). Results: 97% showed evidence of frontal hypometabolism which was most common (100%) in the speech–language (PSP-SL), corticobasal (PSP-CBS), and frontal (PSP-F) variants and least common in the progressive gait freezing (PSP-PGF) variant (73%). PSP-SL and PSP-CBS showed more severe hypometabolism than Richardson's syndrome (PSP-RS), Parkinsonism (PSP-P), and PSP-PGF. A premotor-predominant pattern was most common in PSP-SL and PSP-CBS, with more mixed patterns in the other variants. Hypometabolism was most commonly asymmetric in PSP-SL, PSP-P, PSP-F and PSP-CBS. Worse hypometabolism in nearly all frontal regions correlated with worse scores on the FAB. Conclusions: Frontal hypometabolism is a common finding in PSP, although it varies in severity and pattern across PSP variants and will likely be the most diagnostically useful in PSP-SL and PSP-CBS. [ABSTRACT FROM AUTHOR]

Blastocystis is an intestinal protist frequently identified in humans and other animals, though its clinical significance remains controversial. This study aimed to determine the prevalence and genetic diversity of Blastocystis in faecal samples from symptomatic (n = 55) and asymptomatic (n = 50) individuals seeking medical care in Meknes, Morocco. Detection of the protist was accomplished through coproparasitological examination and culture in Jones medium. Culture-positive samples were subjected to molecular analyses (PCR and Sanger sequencing) based on sequences of the small subunit ribosomal RNA gene. Epidemiological questionnaires on demographics and potential risk factors were collected from participating patients. The overall Blastocystis infection rate was 51.4% (54/105), with no differences between symptomatic (52.7%, 29/55) and asymptomatic (50.0%, 25/50) individuals. Sequence analyses identified three Blastocystis subtypes, with ST3 being the most prevalent (42.0%), followed by ST1 (34.0%), and ST2 (12.0%). Regarding intra-subtype diversity, allele 4 was found within ST1; alleles 11/12 and alleles 34/36 (alone or in combination) were identified within ST2 and ST3 respectively. Allele 34 in ST3 (40.8%) and allele 4 in ST1 (34.7%) were the most common genetic variants circulating in the surveyed clinical population. A statistically significant association between ST2 and the presence of flatulence was observed. This is the first study assessing the epidemiology and genetic diversity of Blastocystis sp. in the Meknes region, Morocco. [ABSTRACT FROM AUTHOR]

Objectives: Tick-borne encephalitis virus Siberian subtype (TBEV-Sib) and Omsk hemorrhagic fever virus (OHFV) are causative agents of natural focal infections in Western Siberia, Russia. The distribution of TBEV phylogenetic lineages and OHFV in the Kemerovo Region of Western Siberia remains poorly investigated. Methods: The phylogenetic analyses of fragment genome sequences 26 flaviviruses identified in 2019 were performed, and the amino acid variation was determined to reveal to which clusteron they belong. The age of Baltic and Asian lineages of the TBEV-Sib was calculated for Kemerovo District and Region, respectively. Results: Twenty-five isolates were members of three TBEV-Sib phylogenetic lineages: Baltic (48%), Asian (36%), and East Siberian (16%). The Baltic lineage's eastern boundary is commonly thought to be in the Novosibirsk Region, but our data suggest that it may reach further east. Analysis of the Baltic lineage clusteron structure showed that the isolates found are unique (6) or belong to clusteron-founder 3D (1) and derived clusteron 3O (5). Based on the age of 3O clusteron, Baltic lineage could have appeared in the Kemerovo Region by the late 1970s. One of the isolated viruses turned out to be the OHFV of the first subtype and not to belong to any known clusteron. This finding is the first known detection of the virus outside the endemic area of Russia. Given the recent discovery of OHFV in Kazakhstan, it can be assumed that the area of this virus distribution is much wider than previously thought. Conclusions: This report provides insights into the population structure of TBEV and OHFV, which may be helpful for epidemiological investigation and surveillance of the viruses. [ABSTRACT FROM AUTHOR]

The ABC classification has recently been proposed as a comprehensive classification system for posterior shoulder instability (PSI). The purpose of this study was to analyze the comprehensiveness as well as inter-rater and intrarater reliability of the ABC classification. All consecutive patients presenting with unidirectional PSI from June 2019 to June 2021 were included in a prospective study. No patients were excluded, leaving a consecutive series of 100 cases of PSI in 91 patients. All recorded clinical and imaging data were used to create anonymized clinical case vignettes, which were evaluated twice according to the ABC classification at the end of the recruitment period in random sequential order by 4 independent raters (2 experienced shoulder surgeons and 2 orthopedic residents) to analyze the comprehensiveness as well as inter-rater and intrarater reliability of the ABC classification for PSI and to describe differences in characteristics among subtypes. Group A was defined as a first-time singular PSI event <3 months in the past regardless of etiology and is further subdivided into type 1 and type 2 depending on the occurrence of a subluxation (A1) or dislocation (A2). Group B comprises recurrent dynamic PSI regardless of time since onset and is further subdivided by the cause of instability into functional (B1) and structural (B2) dynamic PSI. Group C includes chronic static PSI with posterior humeral decentering that can be either constitutional (C1) or acquired (C2). None of the cases was deemed unsuitable to be classified based on the proposed system by the observers. After consensus agreement between the 2 expert raters, 16 cases were attributed to group A (8 type A1 and 8 type A2); 64, to group B (33 type B1 and 31 type B2); and 20, to group C (11 type C1 and 9 type C2). The expert raters agreed on the classification subtypes in 99% and 96% of the cases during the first rating and second rating, respectively (intraclass correlation coefficients [ICCs], 0.998 and 0.99, respectively). The intraobserver reliability was excellent for both raters. The beginners reached the same conclusion as the consensus agreement in 94% of the cases (ICC, 0.99) and 89% of the cases (ICC, 0.97) during the first round and 94% each (ICC, 0.97) during the second round. The intraobserver reliability was excellent for both beginners. Overall, discrepancies between raters were found between groups B1 and B2 (n = 14), groups B2 and C2 (n = 4), groups B1 and C1 (n = 1), and groups A1 and B2 (n = 1). In general, each subtype showed distinctive clinical and imaging characteristics that facilitated the diagnosis. The presented ABC classification for PSI is a comprehensive classification with a high reliability and reproducibility. However, a gradual transition and potential progression between the subtypes of PSI must be considered. The reliable distinction between different subtypes of PSI based on etiology and pathomechanism provides a standardized basis for future investigations on treatment recommendations. [ABSTRACT FROM AUTHOR]

Introduction: Mild cognitive impairment (MCI) is an important stage in Alzheimer's disease (AD) research, focusing on early pathogenic factors and mechanisms. Examining MCI patient subtypes and identifying their cognitive and neuropathological patterns as the disease progresses can enhance our understanding of the heterogeneous disease progression in the early stages of AD. However, few studies have thoroughly analyzed the subtypes of MCI, such as the cortical atrophy, and disease development characteristics of each subtype. Methods: In this study, 396 individuals with MCI, 228 cognitive normal (CN) participants, and 192 AD patients were selected from ADNI database, and a semi-supervised mixture expert algorithm (MOE) with multiple classification boundaries was constructed to define AD subtypes. Moreover, the subtypes of MCI were obtained by using the multivariate linear boundary mapping of support vector machine (SVM). Then, the gray matter atrophy regions and severity of each MCI subtype were analyzed and the features of each subtype in demography, pathology, cognition, and disease progression were explored combining the longitudinal data collected for 2 years and analyzed important factors that cause conversion of MCI were analyzed. Results: Three MCI subtypes were defined by MOE algorithm, and the three subtypes exhibited their own features in cortical atrophy. Nearly one-third of patients diagnosed with MCI have almost no significant difference in cerebral cortex from the normal aging population, and their conversion rate to AD are the lowest. The subtype characterized by severe atrophy in temporal lobe and frontal lobe have a faster decline rate in many cognitive manifestations than the subtype featured with diffuse atrophy in the whole cortex. APOE e4 is an important factor that cause the conversion of MCI to AD. Conclusion: It was proved through the data-driven method that MCI collected by ADNI baseline presented different subtype features. The characteristics and disease development trajectories among subtypes can help to improve the prediction of clinical progress in the future and also provide necessary clues to solve the classification accuracy of MCI. [ABSTRACT FROM AUTHOR]

Ischemic stroke is a major cause of mortality worldwide. Proper etiological subtyping of ischemic stroke is crucial for tailoring treatment strategies. This study explored the utility of circulating microRNAs encapsulated in extracellular vesicles (EV-miRNAs) to distinguish the following ischemic stroke subtypes: large artery atherosclerosis (LAA), cardioembolic stroke (CES), and small artery occlusion (SAO). Using next-generation sequencing (NGS) and machine-learning techniques, we identified differentially expressed miRNAs (DEMs) associated with each subtype. Through patient selection and diagnostic evaluation, a cohort of 70 patients with acute ischemic stroke was classified: 24 in the LAA group, 24 in the SAO group, and 22 in the CES group. Our findings revealed distinct EV-miRNA profiles among the groups, suggesting their potential as diagnostic markers. Machine-learning models, particularly logistic regression models, exhibited a high diagnostic accuracy of 92% for subtype discrimination. The collective influence of multiple miRNAs was more crucial than that of individual miRNAs. Additionally, bioinformatics analyses have elucidated the functional implications of DEMs in stroke pathophysiology, offering insights into the underlying mechanisms. Despite limitations like sample size constraints and retrospective design, our study underscores the promise of EV-miRNAs coupled with machine learning for ischemic stroke subtype classification. Further investigations are warranted to validate the clinical utility of the identified EV-miRNA biomarkers in stroke patients. [ABSTRACT FROM AUTHOR]

The incidence of leiomyosarcoma (LMS) is about 4-5/100,000 individuals per year. LMSs occurring in the small bowel are even rarer, and their preoperative diagnosis is very difficult. We described two patients with pathologically confirmed small bowel LMS and analyzed their clinical and medical imaging features. Similar cases reported in English in Pubmed database over the past decade were reviewed and summarized. These tumors were categorized by the growth direction and relationship with the intestinal lumen into three types: intraluminal (n = 10), intermural (n = 3), and extraluminal (n = 7). Notably, among the three types of LMS, the intramural leiomyosarcoma stands out as a noteworthy subtype. Emerging evidence suggests that smaller tumor size (< 5 cm) and the intraluminal type may serve as favorable prognostic indicators, while the extraluminal type is associated with relatively poor prognosis. Furthermore, the integration of imaging features with CA125 and LDH biomarkers holds promise for potential diagnostic value in LMS. [ABSTRACT FROM AUTHOR]

Objectives: The prevention of mother‐to‐child transmission of HIV has been a global success. But little is known about the growth parameters of infants delivered by mothers with HIV or the drug resistance of infants with HIV in China. The study aimed to assess growth parameters and drug resistance in Chinese infants exposed to HIV. Methods: We conducted an 18‐month longitudinal follow‐up study of 3283 infants (3222 without HIV; 61 with HIV) born to mothers with HIV in the Guangxi Zhuang Autonomous Region between January 2015 and December 2021. The weight and length of all participants was recorded. In addition, genetic subtypes and drug resistance analysis were performed for infants with HIV. Results: Compared with infants without HIV, those with HIV had significantly lower weight/length Z‐scores, except at 18 months of age. The length/age Z‐scores of infants with HIV was significantly reduced, except at 1 month of age. The weight/age Z‐scores of infants with HIV were significantly lower at all follow‐up time points. The weight/length Z‐scores of male infants without HIV were significantly lower than for female infants without HIV at all follow‐up time points. Male infants without HIV had lower length/age and weight/age Z‐scores than female infants at the remaining follow‐up points, except at 1 month of age. Of a total of 61 infants with HIV, subtype and drug‐resistance data were obtained from 37 (60.66%) samples. Infants with HIV were dominated by the CRF01_AE genotype and showed a diversity of mutation sites dominated by non‐nucleoside reverse transcriptase inhibitor resistance. Conclusion: Our study demonstrates the growth of infants exposed to HIV in southwest China and provides detailed information on subtype distribution and drug resistance of those with HIV. Nutritional support and drug‐resistance surveillance for infants exposed to HIV need to be strengthened. [ABSTRACT FROM AUTHOR]

Cryptosporidium spp. are protozoa commonly found in domestic and wild animals. Limited information is available on Cryptosporidium in deer worldwide. In this study, 201 fecal samples were collected from Alpine musk deer on three farms in Gansu Province, China. Detection and subtyping of Cryptosporidium were performed by PCR and sequence analysis of the SSU rRNA and gp60 genes. The prevalence of Cryptosporidium infection in Alpine musk deer was 3.9% (8/201), with infection rates of 1.0% (1/100), 2.8% (1/36), and 9.2% (6/65) in three different farms. All positive samples for Cryptosporidium were from adult deer. Two Cryptosporidium species were identified, including C. parvum (n = 2) and C. xiaoi (n = 6). The C. parvum isolates were subtyped as IIdA15G1, while the C. xiaoi isolates were subtyped as XXIIIa (n = 2) and XXIIIg (n = 4). The IIdA15G1 subtype of C. parvum was found for the first time in deer. These results provide important insights into the identity and human infectious potential of Cryptosporidium in farmed Alpine musk deer. [ABSTRACT FROM AUTHOR]

Introduction: Low self‐esteem is a frequent symptom in major depressive disorder (MDD). This functional magnetic resonance imaging study investigated whether MDD patients with low self‐esteem show a distinct neural pathophysiology. Previous studies linked low self‐esteem to reduced task‐induced deactivation of the pregenual anterior cingulate cortex (pgACC) as a part of the default mode network, and to reduced connectivity between pgACC and reward system. Goya‐Maldonado et al. identified an MDD subtype with pgACC and ventral striatal overactivations during reward processing. We hypothesized that this subtype might be characterized by low self‐esteem. Methods: Eighty‐three MDD patients performed the desire–reason dilemma task and completed the Rosenberg Self‐Esteem Scale (RSES). Brain activity during bottom‐up reward processing was regressed upon the RSES scores, controlling for depression severity measured by the Montgomery–Åsberg Depression Rating Scale. To corroborate the findings, we compared self‐esteem scores between patient subgroups with impaired task‐induced deactivation (n = 31) and with preserved task‐induced deactivation (n = 31) of the pgACC. Results: Consistent with our a priori hypothesis, activity in a bilateral fronto‐striatal network including pgACC and ventral striatum correlated negatively with RSES scores, also when controlling for depression severity. In the additional analysis, patients with impaired task‐induced pgACC deactivation showed lower self‐esteem (t (52.82) = −2.27; p =.027, d = 0.58) compared to those with preserved task‐induced pgACC deactivation. Conclusions: We conclude that low self‐esteem in MDD patients is linked to a task‐induced deactivation dysfunction of the pgACC. Our findings suggest that a previously described possible subtype of MDD with pgACC and ventral striatal overactivations during reward processing is clinically characterized by low self‐esteem. [ABSTRACT FROM AUTHOR]

The distribution of human immunodeficiency virus-1 (HIV-1) subtypes indicates difference from region to region and in risk groups acquiring the disease worldwide. Although subtype C is more in terms of total cases, subtype B is dominant in certain regions, especially in western and central Europe. Molecular epidemiological studies are essential for the control, effective treatment, and understanding in transmission routes of HIV-1 infection. This study aims to determine the molecular epidemiology and antiretroviral drug resistance profiles of HIV-1 in northern Cyprus. The study involved 71 naive HIV-positive patients diagnosed in northern Cyprus between 2016 and 2022. HIV-1 subtypes and circulating recombinant forms (CRFs) were identified by phylogenetic analysis (neighbor-joining method) of pol gene sequences. Drug resistance mutations were analyzed using the World Health Organization (WHO) lists of mutations for surveillance. The Stanford University HIVdb program was used to interpret drug resistance mutations. In our study, 40 of 71 samples were successfully sequenced. Subtype B of HIV-1 was dominant with a rate of 52.5%, followed by CRF02_AG (20%) and G (7.5%) subtypes. The rate of subtype B (71.4%) in northern Cyprus was significantly higher than in the other country of origin (p = .028). Antiretroviral drug resistance was found in 15% of the sequenced serum samples. Nucleoside/nucleotide reverse transcriptase inhibitor (NRTI), non-nucleoside nucleotide reverse transcriptase inhibitor (NNRTI), and protease inhibitor (PI) resistance rates were 10% (4/40), 7.5% (3/40), and 2.5% (1/40), respectively. According to the results, it is noteworthy that the dominant subtype circulating in northern Cyprus is the B subtype, and CRFs were detected at a higher rate than expected. [ABSTRACT FROM AUTHOR]

This study employed a comprehensive genome-mining approach to characterize CRISPR-Cas systems in Lactobacillus delbrueckii strains. The analysis involved retrieving 105 genome sequences to explore the variety, occurrence, and evolution of CRISPR-Cas systems within the species. Homology analysis of spacer sequences in detected CRISPR arrays was conducted to assess the variety of target phages and plasmids. The evolutionary trajectories of spaceromes in each subtype of CRISPR arrays were determined by analyzing acquisition and deletion events under the selection pressure of foreign plasmids and phages. Among the analyzed strains, 53 contained only one CRISPR-Cas locus, 11 had two loci, and 21 featured three loci with complete CRISPR-Cas systems. Subtype designation of the results of current study revealed that 56 % of these systems belong to subtypes I-E/I-C, 23 % to subtypes III-A/III-D, and 17 % to subtype II-A. Notably, certain plasmids were found to be specifically targeted by distinct CRISPR array systems. The comparison of spacer sequences with phage genomes indicated that strains containing only CRISPR-Cas type-I systems targeted a broader range of phages. In conclusion, this study highlights the diversity of the three identified CRISPR-Cas types in L. delbrueckii strains and emphasizes their significant role in defense against phage invasion.

Purpose: To elucidate the clinical characteristics and progression rates of pachychoroid and conventional geographic atrophy (GA). Design: Retrospective, multicenter, observational study. Participants: A total of 173 eyes from 173 patients (38 eyes with pachychoroid GA and 135 with conventional GA) from 6 university hospitals in Japan were included. All patients were Japanese, aged ≥50 years and with fundus autofluorescence images having analyzable image quality. A total of 101 eyes (22 with pachychoroid GA and 79 with conventional GA) were included in the follow-up group. Methods: The studied eyes were classified as having pachychoroid or conventional GA; the former was diagnosed if the eye had features of pachychoroid and no drusen. The GA area was semiautomatically measured on fundus autofluorescence images, and the GA progression rate was calculated for the follow-up group. Multivariable linear regression analysis was used to determine whether the rate of GA progression was associated with GA subtype. Main Outcome Measures: Clinical characteristics and progression rates of pachychoroid and conventional GA. Results: The pachychoroid GA group was significantly younger (70.3 vs. 78.7 years; P < 0.001), more male-dominant (89.5 vs. 55.6%; P < 0.001), and had better best-corrected visual acuity (0.15 vs. 0.40 in logarithm of the minimum angle of resolution; P = 0.002), thicker choroid (312.4 vs. 161.6 μm; P < 0.001), higher rate of unifocal GA type (94.7 vs. 49.6%; P < 0.001), and smaller GA area (0.59 vs. 3.76 mm2; P < 0.001) than the conventional GA group. In the follow-up group, the mean GA progression rate (square-root transformation) was significantly lower in the pachychoroid GA group than in the conventional GA group (0.11 vs. 0.27 mm/year; P < 0.001). Conclusions: Demographic and ocular characteristics differed between GA subtypes. The progression rate of pachychoroid GA, adjusted for age and baseline GA area, was significantly lower than that of conventional GA. Japanese patients with conventional GA showed characteristics and progression rates similar to those in White populations. Some characteristics of GA in Japanese population differ from those in Waucasian populations, which may be due to the inclusion of pachychoroid GA. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Min Yu,1– 3 Zeliang Hao,1– 3 Liyue Xu,4 Long Zhao,4 Yongfei Wen,4 Fang Han,4,&ast; Xuemei Gao1– 3,&ast; 1Department of Orthodontics, Peking University School and Hospital of Stomatology, Beijing, People’s Republic of China; 2Center for Oral Therapy of Sleep Apnea, Peking University Hospital of Stomatology, Beijing, People’s Republic of China; 3National Center for Stomatology, Beijing, 100081, People’s Republic of China; 4Sleep Division, Peking University People’s Hospital, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fang Han, Sleep Division, Peking University People’s Hospital, No. 11 Xizhimen South Street, Xicheng District, Beijing, 100044, People’s Republic of China, Tel +86-010-88324204, Email hanfang1@hotmail.com Xuemei Gao, Department of Orthodontics, Peking University School and Hospital of Stomatology, No. 22 Zhongguancun South Avenue, Haidian District, Beijing, 100081, People’s Republic of China, Tel/Fax +86-010-82195350, Email xmgao@263.netPurpose: Catathrenia is a rare sleeping disorder characterized by repetitive nocturnal groaning during prolonged expirations. Patients with catathrenia had heterogeneous polysomnographic, comorbidity, craniofacial characteristics, and responses to treatment. Identifying phenotypes of catathrenia might benefit the exploration of etiology and personalized therapy.Patients and Methods: Sixty-six patients diagnosed with catathrenia by full-night audio/video polysomnography seeking treatment with mandibular advancement devices (MAD) or continuous positive airway pressure (CPAP) were included in the cohort. Polysomnographic characteristics including sleep architecture, respiratory, groaning, and arousal events were analyzed. Three-dimensional (3D) and 2D craniofacial hard tissue and upper airway structures were evaluated with cone-beam computed tomography and lateral cephalometry. Phenotypes of catathrenia were identified by K-mean cluster analysis, and inter-group comparisons were assessed.Results: Two distinct clusters of catathrenia were identified: cluster 1 (n=17) was characterized to have more males (71%), a longer average duration of groaning events (18.5± 4.8 and 12.8± 5.7s, p=0.005), and broader upper airway (volume 41,386± 10,543 and 26,661± 6700 mm3, p< 0.001); cluster 2 (n=49) was characterized to have more females (73%), higher respiratory disturbance index (RDI) (median 1.0 [0.3, 2.0] and 5.2 [1.2, 13.3]/h, p=0.009), more respiratory effort-related arousals (RERA)(1 [1, 109] and 32 [13, 57)], p=0.005), smaller upper airway (cross-sectional area of velopharynx 512± 87 and 339± 84 mm2, p< 0.001) and better response to treatment (41.2% and 82.6%, p=0.004).Conclusion: Two distinct phenotypes were identified in patients with catathrenia, primary catathrenia, and catathrenia associated with upper airway obstruction, suggesting respiratory events and upper airway structures might be related to the etiology of catathrenia, with implications for its treatment.Keywords: subtype, groaning, upper airway, treatment, OSA, sleep-disordered breathing

Abstract Objective The study aimed to investigate the predictive value of dynamic contrast-enhanced ultrasound (DCE-US) in differentiating small-duct (SD) and large-duct (LD) types of intrahepatic cholangiocarcinoma (ICC). Methods This study retrospectively enrolled 110 patients with pathologically confirmed ICC lesions who were subject to preoperative contrast-enhanced ultrasound (CEUS) examinations between January 2022 and February 2023. Patients were further classified according to the subtype: SD-type and LD-type, and an optimal predictive model was established and validated using the above pilot cohort. The test cohort, consisting of 48 patients prospectively enrolled from March 2023 to September 2023, was evaluated. Results In the pilot cohort, compared with SD-type ICCs, more LD-type ICCs showed elevated carcinoembryonic antigen (p

Abstract Background In this study, the risk of dementia in patients with a history of herpes simplex virus (HSV) or varicella zoster virus (VZV) infection was evaluated. Methods This nationwide cohort study used data from the Korean National Health Insurance Service collected between 2006 and 2017. A total of 752,205 subjects ≥ 45 years of age not diagnosed with dementia until 2006 were included. A multivariate Cox regression model, adjusted for age, sex, and other comorbidities, was used to assess the hazard ratio (HR) for dementia based on VZV or HSV infection. The interaction effects of both viral infections were analysed. Viral infections are classified into four categories: eye, central nervous system (CNS), simple, and complicated. The hazard ratio (HR) of viral infection was analysed based on the type of dementia. Results In multivariable analysis, both HSV and VZV infection were associated with an increased risk of dementia (HR = 1.38, 95% confidence interval, CI:1.33–1.43) and (HR = 1.41, 95% CI:1.37–1.46), respectively. Patients who experienced both HSV and VZV infections were also at an increased risk of dementia (HR = 1.57, 95% CI:1.50–1.63). The co-infection group showed the shortest time from viral infection to dementia diagnosis (4.09 ± 3.02 years). In the subgroup analysis, all types of HSV and VZV infections were associated with an increased risk of dementia compared to the non-infection group. The eye, CNS, and complicated VZV infections were associated with a significantly higher risk than simple VZV infections. There were no significant differences between the subtypes of HSV infection. Furthermore, HSV, VSV, and co-infection were associated with an increased risk of all dementia types, including Alzheimer’s disease (AD) and vascular dementia (VD). Conclusions Individual HSV and VZV infections were associated with an increased risk of all types of dementia, including AD and VD. Patients co-infected with HSV and VZV, VZV infection in the eye, CNS, or complicated type were more vulnerable to the development of dementia.

Cluster analysis of HIV sequence can provide insights into viral transmission patterns in border regions. This study aims to illuminate the HIV-1 subtype distribution and transmission dynamics among newly diagnosed individuals in Dehong prefecture, a region along the China-Myanmar border. Among 948 participants with pol gene sequences, 36 HIV-1 subtypes were identified, with URFs (18.8%, 178/948) being the dominant strain, followed by CRF01_AE (18.5%, 175/948) and CRF07_BC (10.9%, 103/948). Additionally, 287 sequences (30.3%, 287/948) were grouped into 91 clusters, 31 of which contained both Chinese and Burmese individuals. Multivariable logistic regression indicated that men who have sex with men (MSM), CD4 + cell count of 200∼499, and 500 cells/μl and above, and CRF01_AE were risk factors for entering the network. Through the Chord diagram, we found frequent transmission relationships among heterosexual China male group, especially those over 35 years of age. Additionally, the correlation between heterosexual Myanmar female group and heterosexual China male group among cross-risk groups deserved to be emphasized. Furthermore, the network exhibited a growing trend over time, with the largest active transmission cluster identified in Ruili county. In conclusion, the HIV-1 subtype landscape in Dehong has become increasingly complex, and the region has faced risks of transmission from both domestic and international sources. Targeted intervention strategies should be implemented for MSM, heterosexual Chinese middle-aged and elderly men, and heterosexual Burmese young adults to mitigate these risks. These findings provided evidence-based insights for local government to formulate coordinated transnational intervention approaches.

Hepatitis E virus (HEV) and Rat Hepatitis E virus (RHEV), recognized for their zoonotic potential, pose significant public health concerns. Our previous research identified both viruses in effluent wastewater in Gothenburg, Sweden. However, there are lingering inquiries regarding the prevalence and genetic diversity of these viruses in influent wastewater, as well as the utility of wastewater surveillance in elucidating their community circulation dynamics. To address these knowledge gaps, we conducted weekly collection of wastewater samples at the Rya wastewater treatment plant in Gothenburg throughout 2023. The concentrations of HEV and RHEV were quantified using quantitative polymerase chain reaction (qPCR). Additionally, two semi/nested-PCR were utilized to amplify viral strains. Furthermore, HEV strains from patients within the same region, as well as other regions in Sweden in 2023, were incorporated into the analysis. Remarkably, we observed a high prevalence of HEV (86%) and RHEV (98%) in wastewater samples, with the majority of HEV sequences identified as subtype 3c/i (9/12). In contrast, HEV subtype 3f was the most sequenced among clinical patient samples (6/12). Notably, previously unreported HEV-3b and unclassified strains were detected in wastewater. Almost all RHEV strains (20/21) were clustered into European groups, with none of the RHEV genetically close to strains previously found in human cases. The notable discordance in prevalence and identified subtypes of HEV-3 in wastewater compared to clinical samples suggests either a significant underdiagnosis of HEV infections or differences in viral loads and shedding durations among humans between HEV-3 subtypes. This underscores the urgent need for improved diagnostic techniques and heightened awareness of HEV transmission dynamics. Furthermore, the consistent detection of RHEV in wastewater underscores the necessity for further investigations to assess the potential role of RHEV in hepatitis cases of unknown etiology, given that most currently available clinical diagnostic assays fail to detect RHEV.