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Megacities are major sources of anthropogenic fossil fuel CO2 (FFCO2) emissions. The spatial extents of these large urban systems cover areas of 10 000 km2 or more with complex topography and changing landscapes. We present a high-resolution land-atmosphere modelling system for urban CO2 emissions over the Los Angeles (LA) megacity area. The Weather Research and Forecasting (WRF)-Chem model was coupled to a very high-resolution FFCO2 emission product, Hestia-LA, to simulate atmospheric CO2 concentrations across the LA megacity at spatial resolutions as fine as ∼ 1 km. We evaluated multiple WRF configurations, selecting one that minimized errors in wind speed, wind direction, and boundary layer height as evaluated by its performance against meteorological data collected during the CalNex-LA campaign (May-June 2010). Our results show no significant difference between moderate-resolution (4 km) and high-resolution (1.3 km) simulations when evaluated against surface meteorological data, but the high-resolution configurations better resolved planetary boundary layer heights and vertical gradients in the horizontal mean winds. We coupled our WRF configuration with the Vulcan 2.2 (10 km resolution) and Hestia-LA (1.3 km resolution) fossil fuel CO2 emission products to evaluate the impact of the spatial resolution of the CO2 emission products and the meteorological transport model on the representation of spatiotemporal variability in simulated atmospheric CO2 concentrations. We find that high spatial resolution in the fossil fuel CO2 emissions is more important than in the atmospheric model to capture CO2 concentration variability across the LA megacity. Finally, we present a novel approach that employs simultaneous correlations of the simulated atmospheric CO2 fields to qualitatively evaluate the greenhouse gas measurement network over the LA megacity. Spatial correlations in the atmospheric CO2 fields reflect the coverage of individual measurement sites when a statistically significant number of sites observe emissions from a specific source or location. We conclude that elevated atmospheric CO2 concentrations over the LA megacity are composed of multiple fine-scale plumes rather than a single homogenous urban dome. Furthermore, we conclude that FFCO2 emissions monitoring in the LA megacity requires FFCO2 emissions modelling with ∼ 1 km resolution because coarser-resolution emissions modelling tends to overestimate the observational constraints on the emissions estimates.

Although the Flow experience has been researched extensively in music education, there is limited investigation into exploring the link between the Suzuki piano method and Csikszentmihalyi’s flow theory. To address this gap, a quasi-experimental study was conducted to examine how the Suzuki piano method can promote the flow state of adult piano beginners. The study involved 36 participants assigned to either a treatment group or a control group. Both groups underwent an eight-week training program in Suzuki Piano Method and Conventional Group Piano Class respectively. After the program, participants from both groups underwent a post-training performance test and completed a survey, namely Learning and Performing Experience Scale (LPES), modified based on the Short Flow State Scale (S-FFS) by Martin and Jackson to examine their flow experience. The treatment group showed significantly higher flow experience levels than the control group, particularly in dimensions of Concentration, Unambiguous feedback, Timelessness, Loss of self-consciousness, Sense of control, Autotelic experience, and Challenge-skill balance. The findings suggested that the Suzuki piano method may promote flow experiences among adult beginners in piano learning. The implication of the study signified that the collaborative and interactive learning inherent in the method might be beneficial in achieving flow state and could be a consideration in conducting group piano classes.

We investigate the scattering properties of coupled parity-time (PT) symmetric chiral nanospheres with scattering matrix formalism. The exceptional points, i.e., spectral singularities at which the eigenvalues and eigenvectors simultaneously coalesce in the parameter space, of scattering matrix can be tailored by the chirality of the nanospheres. We also calculate the scattering, absorption and extinction cross sections of the PT-symmetric chiral scatter under illumination by monochromatic left- and right-circularly polarized plane waves. We find that the scattering cross section of the nanostructures exhibits an asymmetry when the plane waves are incident from the loss and gain regions, respectively, especially in the broken phase, and the optical cross section exhibits circular dichroism, i.e., differential extinction when the PT-symmetric scatter is endowed with chirality. In particular, under illumination by linearly polarized monochromatic plane waves without intrinsic chirality, the ellipticity of scattered fields in the forward direction, denoting the chirality of light, becomes larger when the scatter is in the PT-symmetry-broken phase. Our findings demonstrate that the gain and loss can control the optical chirality and enhance the chiroptical interactions and pave the way for studying the resonant chiral light–matter interactions in non-Hermitian photonics.

Introduction: Total knee arthroplasty has been adopted to be the most successful treatment for advanced knee osteoarthritis. The adoption of multimodal periarticular analgesic (MPI) has been shown to have satisfactory pain control after surgery. However, there is relatively lack of data investigating whether this mode of pain control is effective in enhancing rehabilitation. Method: This is a prospective randomized control trial from July 2017 to June 2018, including 82 patients, in which 43 of them had MPI injection and 39 of them had no MPI injection. Primary outcome measures included the number of days required to perform straight leg raise, length of hospital stay, and Insall knee score upon discharge. Secondary outcome measures included total dose of patient-controlled analgesia (PCA) consumption postoperatively and visual analog scale (VAS) at rest and on motion during postoperative days 1–4. Result: The MPI group performed significantly better than the femoral nerve block (FNB) group in terms of early functional outcome, namely the number of days required to perform straight leg raising and length of hospital stay. The total postoperative PCA consumption and VAS score on motion during postoperative day 1 were also significantly better for MPI group. There was no difference in Insall knee score upon discharge between these two groups. Conclusion: Compared to FNB, MPI depicts a faster inpatient rehabilitation, accounted by its quadriceps-sparing, and better pain relief especially in the early postoperative period.

AIM: This paper reports a study to determine whether a nurse-initiated telephone follow-up programme could increase patients' self-efficacy in managing dyspnoea and decrease health care service use. BACKGROUND: Chronic obstructive pulmonary disease is a worldwide health problem and has been labelled a burdensome disease. Because of the fear of activity-induced dyspnoea, patients with chronic obstructive pulmonary disease lack the confidence to perform daily activities. Studies of cardiac and diabetic patients have shown that telephone follow-up care is an effective approach to increasing self-efficacy. However, little such research has been done with patients with chronic obstructive pulmonary disease. METHODS: This was a randomized controlled study. A total of 60 participants (30 telephone follow-up, 30 control) with chronic obstructive pulmonary disease were recruited from an acute care hospital in Hong Kong. The Chinese Self-Efficacy Scale was used to assess self-efficacy. Measures of health care use were numbers of visits to an accident and emergency department, hospitalizations, and unscheduled visits by physicians. FINDINGS: The self-efficacy scores (U = 272.5, P = 0.009) of patients who were followed up by telephone improved significantly compared with those of patients in the control group. Multiple regression analyses showed that telephone follow-up (Beta = 0.33, CI: 0.19-0.48, P = 0.001), the pulmonary rehabilitation programme (Beta = 0.44, CI: 0.16-0.72, P = 0.003), smoking (Beta = 0.34, CI: 0.09-0.57, P = 0.009), and health care use (Beta = -0.27, CI: -0.47-(-0.07), P = 0.008) were significant factors in predicting patient self-efficacy. CONCLUSIONS: Nurse-initiated telephone follow-up care was effective in increasing self-efficacy in managing dyspnoea. The study needs to be replicated in other setting to strengthen its external validity. [ABSTRACT FROM AUTHOR]

This article illustrates the clinical course of a patient diagnosed to have bilateral Charcot hip arthropathy secondary to tabes dorsalis from delayed untreated syphilitic infection. This differential diagnosis of rapid bilateral hip destruction was a near-extinct entity, and a high index of suspicion is needed to prevent untoward sequelae.

A case with simultaneous tibial tuberosity fracture and patellar tendon avulsion in a 16-year-old boy is presented. Surgery was performed for open reduction, screw fixation and patellar tendon repair, and protected with a wire loop to restore the extensor mechanism. The wire loop was removed at 2 months postoperatively. The fracture healed at 5 months after surgery and the patient regained the full range of movement of the knee at 5 months.

Background/Purpose Reverse shoulder arthroplasty (RSA) is an effective treatment for patients who suffer from shoulder pain and dysfunction associated with a variety of shoulder pathologies including severe rotator cuff deficiency with or without glenohumeral arthritis. It has been widely used in European countries and the United States and is now gaining popularity in Asia, including Hong Kong. However, there are only limited size options available for glenoid baseplates, with 25 mm being the smallest size in some commonly used systems. The aim of our study is to perform computerized tomography (CT) measurements of the glenoid dimension in the Chinese population and to see if the current glenoid baseplate component size option is sufficient for our local population. Methods A total of 70 CT scans of shoulder regions were analysed. Measurements included maximum superoinferior height and the anteroposterior height. Results The glenoid dimensions were smaller compared to those from previous studies in Caucasian counterparts. Some 41% of female glenoids had widths measuring < 25 mm (25 mm being the smallest size available in some commonly used RSA systems). Conclusion Although there are only limited size options available for the glenoid baseplate in RSA, from our data, it should be able to cover most patients in our local population. However, surgeons should exercise special care when contemplating performing reverse shoulder replacement for small size females in our local population.

Abstract Background MIR129-2 has been shown to be a tumor suppressor microRNA hypermethylated in epithelial cancers. Patients and methods Epigenetic inactivation of MIR129-2 was studied by methylation-specific PCR (MSP) in 13 cell lines (eight myeloma and five lymphoma), 15 normal controls and 344 primary samples including acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML), chronic lymphocytic leukemia (CLL), non-Hodgkin’s lymphoma (NHL), multiple myeloma (MM) at diagnosis, MM at relapse/progression, and monoclonal gammopathy of undetermined significance (MGUS). Expression of MIR129 and its target, SOX4, in cell lines was measured before and after hypomethylating treatment and MIR129 overexpression. MIR129 expression was correlated with MIR129-2 methylation status in primary lymphoma samples. Tumor suppressor function of MIR129 was demonstrated by MTT and trypan blue exclusion assay after MIR129 overexpression. Results The sensitivity of the methylated-MSP was one in 103. Different MSP statuses, including complete methylation, partial methylation, and complete unmethylation, were verified by quantitative bisulfite pyrosequencing. All five lymphoma and seven of eight myeloma cell lines showed complete and partial MIR129-2 methylation. In primary samples, MIR129-2 methylation was absent in AML and CML, but detected in 5% ALL, 45.9% CLL, 49.5% MM at diagnosis, and 59.1% NHL. In CLL, MIR129-2 methylation adversely impacted on survival (p=0.004). In MM, MIR129-2 methylation increased from 27.5% MGUS to 49.5% MM at diagnosis and 41.5% at relapse/progression (p=0.023). In NHL, MIR129-2 methylation was associated with MIR124-1 and MIR203 methylation (pMIR129 expression (p=0.009). Hypomethylation treatment of JEKO-1, homozygously methylated for MIR129-2, led to MIR129-2 demethylation and MIR129 re-expression, with downregulation of SOX4 mRNA. Moreover, MIR129 overexpression in both mantle cell lines, JEKO-1 and GRANTA-519, inhibited cellular proliferation and enhanced cell death, with concomitant SOX4 mRNA downregulation. Conclusions MIR129-2 is a tumor suppressive microRNA frequently methylated in lymphoid but not myeloid malignancies, leading to reversible MIR129-2 silencing. In CLL, MIR129-2 methylation was associated with an inferior survival. In MM, MIR129-2 methylation might be acquired during progression from MGUS to symptomatic MM. In NHL, MIR129-2 methylation might collaborate with MIR124-1 and MIR203 methylation in lymphomagenesis.

Abstract Background MicroRNA (miR) miR-34a, -34b/c, -124-1 and -203 are tumor suppressor miRs implicated in carcinogenesis. Methods We studied DNA methylation of these miRs in Philadelphia-negative (Ph-ve) myeloproliferative neoplasms (MPNs). Methylation-specific PCR (MSP), verified by direct sequencing of the methylated MSP products, was performed in cell lines, normal controls and diagnostic marrow samples of patients with MPNs. Results Methylation of these miRs was absent in the normal controls. miR-34b/c were homozygously methylated in HEL cells but heterozygously in MEG-01. In HEL cells, homozygous miR-34b/c methylation was associated with miR silencing, and 5-aza-2'-deoxycytidine treatment led to re-expression of both miR-34b and miR-34c, consistent with that both miRs are under the regulation of the same promoter CpG island. miR-34a was heterozygously methylated in MEG-01 and K-562. miR-203 was completely unmethylated in K-562 and SET-2 but no MSP amplification was found in both HEL and MEG-01, suggestive of miR deletion. In primary samples, four each had miR-34b/c and -203 methylation, in which two had concomitant methylation of miR-34b/c and -203. miR-34a was methylated in one patient and none had methylation of miR-124-1. Seven patients (15.6%) had methylation of at least one of the four miRs. miR methylation did not correlate with clinical parameters, disease complications or JAK2 V617F mutation. Conclusion This is the first report of miR hypermethylation in MPNs. miR-203 hypermethylation is not specific to Ph+ve leukemias but also present in Ph-ve MPNs. miR-34b/c methylation was associated with reversible miR silencing. There was no correlation of miR methylation with clinical demographic data or outcome.

Embryonic stem cells possess the remarkable ability to self-organize into blastocyst-like structures upon induction. These stem cell-based embryo models serve as invaluable platforms for studying embryogenesis and therapeutic developments. Nevertheless, the specific intrinsic regulators that govern this potential for blastoid formation remain unknown. Here we demonstrate an intrinsic program that plays a crucial role in both blastoids and blastocysts across multiple species. We first establish metrics for grading the resemblance of blastoids to mouse blastocysts, and identify the differential activation of gene regulons involved in lineage specification among various blastoid grades. Notably, abrogation of nuclear receptor subfamily 1, group H, member 2 (Nr1h2) drastically reduces blastoid formation. Nr1h2 activation alone is sufficient to rewire conventional ESC into a distinct pluripotency state, enabling them to form blastoids with enhanced implantation capacity in the uterus and contribute to both embryonic and extraembryonic lineages in vivo. Through integrative multi-omics analyses, we uncover the broad regulatory role of Nr1h2 in the transcriptome, chromatin accessibility and epigenome, targeting genes associated with embryonic lineage and the transposable element SINE-B1. The Nr1h2-centred intrinsic program governs and drives the development of both blastoids and early embryos., Competing Interests: Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Purpose: Antibodies to select Epstein-Barr virus proteins can diagnose early-stage nasopharyngeal carcinoma (NPC). We have previously shown that IgA against Epstein-Barr virus nuclear antigen 1 (EBNA1) can predict incident NPC in high- and intermediate-risk cohorts 4 years before diagnosis. Here, we tested EBNA1 variants, with mutants, to define the sequence requirements for an NPC risk assay., Experimental Design: Mammalian-expressed constructs were developed to represent EBNA1 variants 487V and 487A, which can differ by ≥15 amino acids in the N- and C-termini. Denatured lysates were evaluated by a refined IgA and IgG immunoblot assay in a case-control study using prediagnostic NPC sera from two independent cohorts in Singapore and Shanghai, the People's Republic of China., Results: At 95% sensitivity, 487V yielded a 94.9% specificity compared with 86.1% for 487A. EBNA1 deleted for the conserved glycine-alanine repeats (GAr) reduced false positives by 22.8%. NPC sera reacted more strongly to the C-terminus than healthy controls, but the C-terminal construct (a.a. 390-641) showed lower specificity (84.8%) than the EBNA1 GAr-deleted construct (92.4%) at 95% sensitivity., Conclusions: Although EBNA1 IgA was present in healthy sera, most epitopes localized to the immunodominant GAr. We conclude that a refined EBNA1 antigen deleted for the GAr, but with residues consistently detected in Southeast Asian NPC tumors, is optimized for risk prediction with an extended sojourn time of 7.5 years. Furthermore, distinct EBNA1 serologic profiles enhanced the utility of the EBNA1 IgA assay for risk stratification. This illustrates the importance of serologically relevant EBNA1 sequences for NPC risk prediction and early detection., (©2024 American Association for Cancer Research.)

Key Clinical Message: Lumbar facet fracture-dislocation is rare, often due to hyperflexion with rotational force. Abnormal scoliosis on radiography is a key sign, prompting further imaging. Facetectomy and laminectomy ensure safe reduction, while instrumented fusion is an effective surgical treatment., Abstract: Traumatic lumbar facet dislocation is an uncommon condition, particularly when unilateral lumbar facet dislocation is accompanied by a contralateral facet fracture. The patient had a locked facet joint at the left L4-L5, a fracture of the right superior articular process of L5 and a comminuted fracture at the peritrochanteric region of the right femur following a fall. Emergent operation was conducted, starting with open reduction and fixation for the right proximal femur, followed by posterior open reduction and posterolateral fusion with instrumentation, without interbody fusion, for the lumbar spine injury. The patient exhibited positive outcomes throughout the follow-up. This article highlights the trauma mechanism of lumbar facet dislocation, emphasizing hyperflexion with rotational force. Abnormal local scoliosis is a distinctive imaging sign of facet joint dislocation. Facetectomy and laminectomy are recommended for safe reduction and instrumented fusion is considered a safe and effective surgical treatment for facet joint dislocation injuries., Competing Interests: None of the authors had any conflict of interest in relation to this report., (© 2024 The Author(s). Clinical Case Reports published by John Wiley & Sons Ltd.)

Wearable haptics serve as an enhanced media to connect humans and VR/robots. The inevitable sweating issue in all wearables creates a bottleneck for wearable haptics, as the sweat/moisture accumulated in the skin/device interface can substantially affect feedback accuracy, comfortability, and create hygienic problems. Nowadays, wearable haptics typically gain performance at the cost of sacrificing the breathability, comfort, and biocompatibility. Here, we developed a fully integrated breathable haptic textile (FIBHT) to solve these trade-off issues, where the FIBHT exhibits high-level integration of 128 pixels over the palm, great stretchability of 400%, and superior permeability of over 657 g/m 2 /day (moisture) and 40 mm/s (air). It is a stand-alone haptic system totally composed of stretchable, breathable, and bioadhesive materials, which empowers it with precise, sweating/movement-insensitive and dynamic feedback, and makes FIBHT powerful for virtual touching in broad scenarios.

Background: Metabolic surgery is recognized for its effectiveness in weight loss and improving outcomes for individuals with type 2 diabetes mellitus (T2DM). However, its impact on renal function, especially in multi-ethnic Asian populations, remains underexplored. This study investigates mid- and long-term renal outcomes following metabolic surgery in Asian patients with T2DM., Methods: This retrospective cohort study utilized data from the Asian Diabetes Surgery Study (ADSS), involving T2DM patients aged 20-79 who underwent metabolic surgery from 2008 to 2015. The primary outcome was the change in estimated glomerular filtration rate (eGFR) at 1, 3, and 5 years post-surgery, with adjustments for confounders. Secondary outcomes included changes in chronic kidney disease (CKD) stages and the relationship between weight loss and eGFR changes. Data were analyzed using univariate and multivariable regression analyses, along with the McNemar test., Results: The study included 1513 patients with a mean age of 42.7 years. The results revealed that a significant improvement in eGFR was observed at 1-year post-surgery (112.4 ± 32.0 ml/min/1.73 m², P  < .001), with a shift toward less severe CKD stages. However, this improvement was not sustained at 3 and 5 years. No significant correlation was found between weight loss and eGFR changes at 1-year follow-up., Conclusion: Metabolic surgery significantly improves renal function at 1 year postoperatively in Asian individuals with T2DM, highlighting its potential benefits beyond glycemic control and weight loss. The long-term effects on renal function require further investigation., Competing Interests: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

For emergency medicine physicians, being named in a malpractice suit is not an if, it is a when. By the age of 55 years, 68% of emergency physicians have been sued. In the following article, we review the most common factors shared by closed claims in adult and pediatric patients from emergency departments and acute care settings. Our hope is that by identifying shared characteristics, we may improve patient care and reduce litigation risk., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: Mass Casualty Incidents (MCIs) involving high-speed passenger ferries (HSPFs) may result in the dual-wave phenomenon, in which the emergency department (ED) is overwhelmed by an initial wave of minor injuries, followed by a second wave of more seriously injured victims. This study aimed to characterize the time pattern of ED presentation of victims in such accidents in Hong Kong., Methods: All HSPF MCIs from 2005 to 2015 were reviewed retrospectively, with the time interval from accident to ED registration determined for each victim. Multivariable linear regression was used to identify independent factors associated with the time of ED presentation after the accidents., Results: Eight MCIs involving 492 victims were identified. Victims with an Injury Severity Score (ISS) ≥ 9 had a significantly shorter median time interval compared to those with minor injuries. An ISS ≥ 9 and evacuation by emergency service vessels were associated with a shorter delay in ED arrival, whereas ship sinking, accident at nighttime, and a longer linear distance between the accident and receiving ED were associated with a longer delay., Conclusion: The dual-wave phenomenon was not present in HSPF MCIs. Early communication is the key to ensure early resource mobilisation and a well-timed response.

Given a maze (e.g., in a book of puzzles), you might solve it by drawing out paths with your pencil. But even without a pencil, you might naturally find yourself mentally tracing along various paths. This "mental path tracing" may intuitively seem to depend on your (overt, conscious, voluntary) goal of wanting to get out of the maze, but might it also occur spontaneously-as a result of simply seeing the maze, via a kind of dynamic visual routine? Here, observers simply had to compare the visual properties of two probes presented in a maze. The maze itself was entirely task irrelevant, but we predicted that simply seeing the maze's visual structure would "afford" incidental mental path tracing (à la Gibson). Across four experiments, observers were slower to compare probes that were further from each other along the paths, even when controlling for lower level properties (such as the probes' brute linear separation, ignoring the maze "walls"). These results also generalized beyond mazes to other unfamiliar displays with task-irrelevant circular obstacles. This novel combination of two prominent themes from our field-affordances and visual routines-suggests that at least some visual routines may not require voluntary goals; instead, they may operate in an automatic (incidental, stimulus-driven) fashion, as a part of visual processing itself. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Objective: To evaluate the factors that improve professional and personal well-being amongst women in neonatology (WiN)., Study Design: A 30-question survey of multiple choice, rank order, and open-ended questions focused on professional and personal factors that affect the well-being of WiN members. Quantitative and qualitative methods were used to determine leading factors and themes., Results: Of 326 respondents, 64% felt "well" professionally over half of the time. Professional well-being was most affected by scheduling flexibility, helping patients, administrative and staffing support, feelings of being valued, and clinical workload/acuity. Time for family and self-care, having domestic help, and scheduling flexibility were factors that most positively impacted personal well-being., Conclusion: In this national survey, WiN members identified the factors that can improve their well-being. Strategic planning and targeted interventions are urgently needed to enhance work-life integration and job satisfaction, leading to improved neonatal workforce retention and improved quality of patient care., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: Autologous bone dust can be filled in bone defects to promote effective bone healing but typically it is lost when using suction during surgery. The aim of this study was to develop a novel bone collector that can be used to collect bone chips/dust of varying sizes without changing current surgical procedures., Research Design and Methods: This collector was designed to connect to a surgical continuous suction system and comprised a plate filter with a 3 mm hole and featured a taper filter with a mesh size of 0.27 mm for the separation and collection of both coarse and fine bone chips/dust. The bone collector was manufactured using nylon 3D printing and plastic injection with biocompatible materials., Results: The bone collector functional test revealed high bone chip collection efficiency (93%) with automatic size separation function. Low (3.42%) filtration errors showed that most of the water can be drained smoothly from the bone collector. In clinical usability testing, bone collectors can provide functions demonstrated in in vivo spinal fusion and femoral fracture surgeries with different bone grafting size requirements., Conclusions: The novel bone collector has been validated as a viable and effective surgical device, offering surgeons an additional option to enhance patient outcomes.

Tuberculosis-affected lungs with chronic inflammation harbor abundant immunosuppressive immune cells but the nature of such inflammation is unclear. Dysfunction in T cell exhaustion, while implicated in chronic inflammatory diseases, remains unexplored in tuberculosis. Given that immunotherapy targeting exhaustion checkpoints exacerbates tuberculosis, we speculate that T cell exhaustion is dysfunctional in tuberculosis. Using integrated single-cell RNA sequencing and T cell receptor profiling we reported defects in exhaustion responses within inflamed tuberculosis-affected lungs. Tuberculosis lungs demonstrated significantly reduced levels of exhausted CD8+ T cells and exhibited diminished expression of exhaustion-related transcripts among clonally expanded CD4+ and CD8+ T cells. Additionally, clonal expansion of CD4+ and CD8+ T cells bearing T cell receptors specific for CMV was observed. Expanded CD8+ T cells expressed the cytolytic marker GZMK. Hence, inflamed tuberculosis-affected lungs displayed dysfunction in T cell exhaustion. Our findings likely hold implications for understanding the reactivation of tuberculosis observed in patients undergoing immunotherapy targeting the exhaustion checkpoint., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Genetic variants in Epstein-Barr virus (EBV) have been strongly associated with nasopharyngeal carcinoma (NPC) in South China. However, different results regarding the most significant viral variants, with polymorphisms in EBER2 and BALF2 loci, have been reported in separate studies. In this study, we newly sequenced 100 EBV genomes derived from 61 NPC cases and 39 population controls. Comprehensive genomic analyses of EBV sequences from both NPC patients and healthy carriers in South China were conducted, totaling 279 cases and 227 controls. Meta-analysis of genome-wide association study revealed a 4-bp deletion downstream of EBER2 (coordinates, 7188-7191; EBER-del) as the most significant variant associated with NPC. Furthermore, multiple viral variants were found to be genetically linked to EBER-del forming a risk haplotype, suggesting that multiple viral variants might be associated with NPC pathogenesis. Population structure and phylogenetic analyses further characterized a high risk EBV lineage for NPC revealing a panel of 38 single nucleotide polymorphisms (SNPs), including those in the EBER2 and BALF2 loci. With linkage disequilibrium clumping and feature selection algorithm, the 38 SNPs could be narrowed down to 9 SNPs which can be used to accurately detect the high risk EBV lineage. In summary, our study provides novel insight into the role of EBV genetic variation in NPC pathogenesis by defining a risk haplotype of EBV for downstream functional studies and identifying a single high risk EBV lineage characterized by 9 SNPs for potential application in population screening of NPC., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Wong et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)