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Alicia Blackmore,1 Holly Etchegary,1,2 Leigh Anne Allwood-Newhook,3 Zhiwei Gao,1 Hai Van Nguyen,4 Kaylah Parsons-Mercer,5 Laurie Twells1 1Faculty of Medicine, Memorial University of Newfoundland, St. John’s, Newfoundland and Labrador, Canada; 2Scientific Patient Engagement Lead of NL SUPPORT Unit, St. John’s, Newfoundland and Labrador, Canada; 3Department of Pediatrics, Faculty of Medicine, Memorial University of Newfoundland, St. John’s, Newfoundland and Labrador, Canada; 4School of Pharmacy, Memorial University of Newfoundland, St. John’s, Newfoundland and Labrador, Canada; 5Patient Partner, St. John’s, Newfoundland and Labrador, CanadaCorrespondence: Alicia Blackmore, Faculty of Medicine, Memorial University of Newfoundland, St. John’s, Newfoundland and Labrador, Canada, Email Akt104@mun.caPurpose: Patient-oriented research (POR) and patient engagement (PE) has highlighted the value of incorporating patients’ ideas and priorities in health research. Using the guiding principles of POR and PE, the current study conducted PE sessions to gain insight on the perceptions of mothers regarding the costs of infant feeding.Methods: Four patient engagement sessions were held with mothers residing in Newfoundland and Labrador between November 2019 and January 2020. Mothers were targeted through the Brighter Futures Coalition of St. John’s, a not-for-profit community organization. PE sessions were designed in a two-hour format, allowing the research team to engage mothers and identify costs of infant feeding from a mothers’ perspective.Results: Through the guiding principles of patient-oriented research and patient engagement, our research team successful engaged with mothers in discussions surrounding the costs of infant feeding. The sessions allowed for an in-depth discussion surrounding monetary costs (eg, incidentals of breast or formula feeding), the associated costs of infant feeding and the workplace (eg, perceived productivity) and environment impacts (eg, single use plastics). During each session, evaluations were provided to solicit feedback on whether the goals and expectations of mothers had been met, and whether they felt their opinions were heard and understood.Conclusion: By conducting patient engagement sessions, informed by patient-oriented research guiding principles, we were able to successfully recruit and engage mothers in discussions that led to a better understanding of their perspectives on the costs of infant feeding.Keywords: patient engagement, infant feeding, patient-oriented research

Giao Huynh,1 Hau Viet Nguyen,2 Lan Y Vo,1 Ngoc Thi Le,3 Han Thi Ngoc Nguyen4 1Faculty of Public Health, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam; 2Emergency Department, University Medical Center Ho Chi Minh City, Ho Chi Minh City, Vietnam; 3Faculty of Medicine, Nguyen Tat Thanh University, Ho Chi Minh City, Vietnam; 4Infection Control Department, University Medical Center Ho Chi Minh City, Ho Chi Minh City, VietnamCorrespondence: Hau Viet Nguyen, Emergency Department, University Medical Center Ho Chi Minh City, 215 Hong Bang Street, District 5, Ho Chi Minh City, Vietnam, Tel +84918764092, Email hau.nv@umc.edu.vn Han Thi Ngoc Nguyen, Infection Control Department, University Medical Center Ho Chi Minh City, 201 Nguyen Chi Thanh Street, District 5, Ho Chi Minh City, Vietnam, Tel +84397975519, Email han.ntn2@umc.edu.vnIntroduction: The COVID-19 pandemic has been affecting the lives of millions of people globally. Patients recovering from COVID-19 are facing, not only the symptom of long COVID, but also psychological problems, such as sleep disturbance. This study aims to assess the proportion of COVID-19 recovered adult patients that suffer from insomnia and associated factors in Vietnam.Methods: A cross-sectional study was performed between January and March 2022 among patients who have recovered from a COVID-19 infection. Data were collected based on a self-administered questionnaire that included sociodemographic and standardized questionnaires from the Hospital Anxiety and Depression Scale (HADS), the Perceived stress scale (PSS) and the dependent variable using Insomnia Severity Index (ISI). Multivariable logistic regression was conducted to explore factors associated with the patients’ insomnia disorder.Results: A total of 325 participants were included in this analysis, 34.5% of participants had insomnia. According to multivariable logistic regression, participants who were equal to and over 50 years of age, feeling alienated from others, and were not supported by families or relatives, reported significantly higher levels of insomnia disorders over those aged under 50 years, having closer ties with family and had received support from family or relatives. Besides, respondents who recorded mental health problems that included anxiety, depression and stress were more likely to get insomnia disorders than those without mental health symptoms (OR 2.7, 95% CI 1.1– 6.6) (OR 4.5, 95% CI 2.3– 8.9) (OR 2.3, 95% CI 1.1– 5.3), respectively, all p < 0.05.Conclusion: There was a remarkable rate of COVID-19 recovered patients experiencing insomnia disorders. Older age, alienated relationships and not being supported by families or relatives, as well as had mental health problems, are factors that affected the patients’ insomnia, which showed that these sleep issues need to be screened and managed among adults who have recovered from COVID-19.Keywords: COVID-19, insomnia, recovery, sleep disturbance, Vietnam

Huan Thanh Nguyen,1,2 Huong Thanh Do,2 Hai Van Be Nguyen,2 Tan Van Nguyen1,3 1Department of Geriatrics and Gerontology, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam; 2Department of Cardiology, Thong Nhat Hospital, Ho Chi Minh City, Vietnam; 3Department of Interventional Cardiology, Thong Nhat Hospital, Ho Chi Minh City, VietnamCorrespondence: Huan Thanh Nguyen, Department of Geriatrics and Gerontology University of Medicine and Pharmacy at Ho Chi Minh City, 17 Hong Bang Street, Ward 11, District 5, Ho Chi Minh City, Vietnam, Tel +84-909097849, Email huannguyen@ump.edu.vnPurpose: To investigate the prevalence and factors associated with frailty and impact of frailty on hospitalization due to any cause in elderly patients with chronic coronary syndrome (CCS).Patients and Methods: We conducted a study wherein we assessed frailty using Fried frailty phenotype for outpatients aged ≥ 60 years with CCS. Logistic regression analysis was performed to assess the factors associated with frailty. Frailty was adjusted for demographic and geriatric variables and comorbidities to assess its impact on hospitalization.Results: Overall, 420 patients (median age 70 years [interquartile range, 65– 77]; men, 74.5%) who completed the 3-month follow-up period were analyzed. Coronary revascularization for > 1 year was the most common clinical scenario for CCS (59.8%; n = 251). The prevalence of non-frail, pre-frail, and frail patients were 22.4% (n = 94), 49.7% (n = 209), and 27.9% (n = 117), respectively. In the adjusted model, three factors associated with frailty were age ≥ 75 years (odds ratio [OR] 2.29, 95% confidence interval [CI] 1.39– 3.75, P = 0.001), limitations in instrumental activity of daily living (OR 3.89, 95% CI 2.33– 6.48, P < 0.001), and heart failure (OR 2.30, 95% CI 1.32– 4.02, P = 0.003). The overall 3-month hospitalization rate was higher in frail patients than in non-frail patients (23.9% vs 13.5%, P = 0.012). Frailty was associated with hospitalization (OR 1.85, 95% CI 1.04– 3.30, P = 0.037) but in a weak strength of association (r = 0.126).Conclusion: The prevalence of frailty was 27.9% in the elderly patients with CCS. Age ≥ 75 years, limitations in functional status, and heart failure were associated with increased odds of frailty. Frailty was a predictor of 3-month all-cause hospitalization in these patients.Keywords: frailty, chronic coronary syndrome, elderly

The branched-chain amino acid, leucine, acts as a nutrient signal to stimulate protein synthesis in skeletal muscle of young pigs. However, the chemical structure responsible for this effect has not been identified. We have shown that the other branched-chain amino acids, isoleucine and valine, are not able to stimulate protein synthesis when raised in plasma to levels within the postprandial range. In this study, we evaluated the effect of leucine, alpha-ketoisocaproic acid (KIC), and norleucine infusion (0 or 400 micromol kg(-1) h(-1) for 60 min) on protein synthesis and activation of translation initiation factors in piglets. Infusion of leucine, KIC, and norleucine raised plasma levels of each compound compared with controls. KIC also increased (P < 0.01) and norleucine reduced (P < 0.02) plasma levels of leucine compared with controls. Administration of leucine and KIC resulted in greater (P < 0.006) phosphorylation of eukaryotic initiation factor (eIF) 4E binding protein-1 (4E-BP1) and eIF4G, lower (P < 0.04) abundance of the inactive 4E-BP1.eIF4E complex, and greater (P < 0.05) active eIF4G.eIF4E complex formation in skeletal muscle compared with controls. Protein synthesis in skeletal muscle was greater (P < 0.02) in leucine- and KIC-infused pigs than in those in the control group. Norleucine infusion did not affect muscle protein synthesis or translation initiation factor activation. In liver, neither protein synthesis nor activation of translation initiation factors was affected by treatment. These results suggest that the ability of leucine to act as a nutrient signal to stimulate skeletal muscle protein synthesis is specific for leucine and/or its metabolite, KIC. [ABSTRACT FROM AUTHOR]

The rapid evolution of multifunctional electronics necessitates interconnection technologies appropriate for large dies with high-density and/or ultrafine pitch input/output pins. Existing technologies face numerous challenges, including demands for bonding equipment that can deliver extremely high force as well as thermo-mechanical stresses induced in the assembled packages due to mismatched thermal expansion of materials involved. This study proposes an approach to compliant interconnects comprising single micrometer-sized metal-coated polymer spheres, being joined to mating electrodes by sintering of Ag nano ink at low temperature (140 °C) and low pressure (∼15 mN/particle). Such an interconnection technology is expected to enhance the thermo-mechanical robustness of the assembled packages as well as be capable of high-density, ultrafine pitch interconnects. Our approach demonstrates control over conductive particles during assembly, achieving a 98% success rate in individual interconnects with a single captured particle. The use of sintered Ag not only secures free-standing particles on electrical pads (with an adhesion force above 2 μN) but also results in a 15% reduction in interconnect resistance, with measured resistance as low as 0.5 Ω, compared to interconnects without Ag ink. This method presents an alternative to metallurgical joints, particularly suited for high-density, ultrafine pitch applications, offering low bonding pressure and temperature, along with improved interconnect compliance to enhance the thermo-mechanical robustness of the packages.

GLABRA2 (GL2), a class IV homeodomain leucine-zipper (HD-Zip IV) transcription factor from Arabidopsis, is a developmental regulator of specialized cell types in the epidermis. GL2 contains a monopartite nuclear localization sequence (NLS) that is conserved in most HD-Zip IV members across the plants. We demonstrate that NLS mutations affect nuclear transport and result in a loss-of-function phenotypes. NLS fusions to enhanced yellow fluorescent protein (EYFP) show that it is sufficient for nuclear localization in roots and trichomes. Despite partial overlap of the NLS with the homeodomain, genetic dissection indicates that nuclear localization and DNA binding are separable functions. Affinity purification of GL2 from plants followed by MS-based proteomics identified importin α (IMPα) isoforms as potential GL2 interactors. NLS structural prediction and molecular docking studies with IMPα-3 revealed major interacting residues. Cytosolic yeast two-hybrid assays and co-immunoprecipitation experiments with recombinant proteins verified NLS-dependent interactions between GL2 and several IMPα isoforms. IMPα triple mutants (impα-1,2,3) exhibit abnormal trichome formation and defects in GL2 nuclear localization in trichomes, consistent with tissue-specific and redundant functions of IMPα isoforms. Taken together, our findings provide mechanistic evidence for IMPα-dependent nuclear localization of GL2 in Arabidopsis, a process that is critical for cell type differentiation of the epidermis., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Conjugation of a therapeutic agent to a polymer for enhanced delivery into target cells followed by its intracellular triggered release has proved to be an effective drug delivery approach. This approach is applied to the delivery of the immune-stimulatory unmethylated cytosine-phosphate-guanine (CpG) oligonucleotide for an anti-tumour immune response after intratumoral administration. On average four CpG-1668 molecules were covalently linked to a 40-kDa amino-functionalised dextran polymer via either a non-reversible (CpG-dextran) or an intracellular redox-responsive disulfide linkage (CpG-SS-dextran). Dynamic light scattering analysis showed that both conjugates had a similar particle size and surface charge of 17 nm and -10 mV, respectively. Agarose gel electrophoresis analysis showed that CpG-SS-dextran was stable in the extracellular low glutathione (GSH) concentration range (i.e. 10-20 μM) and was cleaved at the higher intracellular GSH concentration (5 mM), while CpG-dextran was stable in both GSH concentrations. Uptake and activation assays on bone-marrow-derived dendritic cells showed no significant difference between free CpG, CpG-dextran and CpG-SS-dextran. In a mouse subcutaneous colorectal tumour model the CpG-SS-dextran showed a statistically significantly greater inhibition of tumour growth (p < 0.03) and prolonged survival (p < 0.001) compared to CpG-dextran or free CpG. These results demonstrate that the redox-triggered intracellular release of CpG from a dextran polymer carrier has promise for intratumoral therapeutic vaccination against cancer., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Greg Walker reports equipment, drugs, or supplies was provided by University of Otago. Greg Walker reports a relationship with University of Otago that includes: employment. If there are other authors, they 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 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objective: Life satisfaction pertains to an individual's subjective evaluation of their life quality, grounded in their personal criteria. It stands as a crucial cognitive aspect of subjective wellbeing, offering a reliable gauge of a person's comprehensive wellbeing status. In this research, our objective is to develop a hybrid self-supervised model tailored for predicting individuals' life satisfaction in South Korea., Methods: We employed the Busan Metropolitan City Social Survey Data in 2021, a comprehensive dataset compiled by the Big Data Statistics Division of Busan Metropolitan City. After preprocessing, our analysis focused on a total of 32,390 individuals with 51 variables. We developed the self-supervised pre-training TabNet model as a key component of this study. In addition, we integrated the proposed model with the Local Interpretable Model-agnostic Explanation (LIME) technique to enhance the ease and intuitiveness of interpreting local model behavior., Results: The performance of our advanced model surpassed conventional tree-based ML models, registering an AUC of 0.7778 for the training set and 0.7757 for the test set. Furthermore, our integrated model simplifies and clarifies the interpretation of local model actions, effectively navigating past the intricate nuances of TabNet's standard explanatory mechanisms., Conclusion: Our proposed model offers a transparent understanding of AI decisions, making it a valuable tool for professionals in the social sciences and psychology, even if they lack expertise in data analytics., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Nguyen and Byeon.)

Spinal epidural hematoma (SEDH) is a rare but serious complication associated with spinal anesthesia (SA). We present an unusual case of cervical SEDH occurring 24 h after a lumbar puncture for a cesarean section. The patient, who was on low-dose aspirin due to preeclampsia, initially exhibited neurological symptoms resembling a stroke. Despite a normal magnetic resonance imaging (MRI) of the brain, further investigations revealed a SEDH located between the C3 and T1 segments, well beyond the L3-L4 puncture site. Although coagulation tests were normal, this case underscores the potential risk of low-dose aspirin in affecting platelet function, which may contribute to SEDH development. It also emphasizes the importance of considering spinal MRI when neurological symptoms arise after SA, even if initial cranial MRI results are normal. She underwent emergency C3-T1 laminectomy through a dorsal midline approach. Her motor, sensory, and sphincter functions fully recovered at follow-up., Competing Interests: The authors declared no conflicts of interest., (Copyright © 2024 Kham Van Vu et al.)

Sodium (Na)-metal batteries (SMBs) are considered one of the most promising candidates for the large-scale energy storage market owing to their high theoretical capacity (1,166 mAh g -1 ) and the abundance of Na raw material. However, the limited stability of electrolytes still hindered the application of SMBs. Herein, sulfolane (Sul) and vinylene carbonate (VC) are identified as effective dual additives that can largely stabilize propylene carbonate (PC)-based electrolytes, prevent dendrite growth, and extend the cycle life of SMBs. The cycling stability of the Na/NaNi 0.68 Mn 0.22 Co 0.1 O 2 (NaNMC) cell with this dual-additive electrolyte is remarkably enhanced, with a capacity retention of 94% and a Coulombic efficiency (CE) of 99.9% over 600 cycles at a 5 C (750 mA g -1 ) rate. The superior cycling performance of the cells can be attributed to the homogenous, dense, and thin hybrid solid electrolyte interphase consisting of F- and S-containing species on the surface of both the Na metal anode and the NaNMC cathode by adding dual additives. Such unique interphases can effectively facilitate Na-ion transport kinetics and avoid electrolyte depletion during repeated cycling at a very high rate of 5 C. This electrolyte design is believed to result in further improvements in the performance of SMBs., (© 2024 Wiley‐VCH GmbH.)

Objective: In dermatological research, the focus on scalp and skin health has intensified, particularly regarding prevalent conditions like dandruff and erythema. This study aimed to utilize YOLOv7 model to develop an automated detection web-based system for these specific scalp lesions., Methods: Utilizing a dataset of 2200 clinical images, the model's accuracy and robustness were assessed. The raw images were initially preprocessed by the Roboflow tool. We then trained and evaluated the YOLOv7 model, comparing its performance with several baseline models including YOLOv5, YOLOF, and the single-shot detector. Finally, the proposed model was integrated into a flask API-based web application using the flask-ngrok library., Results: The YOLOv7 demonstrated exceptional performance, attaining a mean average precision of 98.6%, with precision and recall rates of 98.6% and 97.2%, respectively. When benchmarked against baseline models, the YOLOv7 demonstrated enhanced performance metrics both during the training phase and the testing process on unseen data., Conclusions: This study not only validates the potential of YOLOv7 for scalp lesion diagnostic applications but also brings the integration of sophisticated AI models into practical healthcare solutions., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Background: Supplementing probiotics in livestock feed is increasing due to concerns over the potential harm caused by antibiotics and other chemical growth promoters. Several Bacillus sp. have been used as probiotic supplements for livestock. In this study, Bacillus amyloliquefaciens S2.5 was isolated from freshwater and its potential probiotic characteristics were evaluated in vitro. The whole genome of strain S2.5 was sequenced, and its probiotic traits were annotated using bioinformatic tools., Results: Both vegetative cells and spores of strain S2.5 remained stable throughout the 1.5 h of gastric juice and 48 h of intestine simulation. The strain S2.5 harbored the ability to produce glucoamylase, carboxymethyl cellulase, protease, and chitinase. It is also susceptible to all six tested antibiotics. The complete genome sequence shows genes related to acid-bile tolerance, environmental stress resistance, hydrolases, and adhesion to gut mucosa, confirming probiotic traits in the in vitro experiments., Conclusions: B. amyloliquefaciens S2.5 demonstrated potential probiotic characteristics and its genetic profile in the in vitro experiments. Further in vivo assessments of B. amyloliquefaciens S2.5 on livestock and poultry should be performed to assess its practical application., 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 The Authors. Published by Elsevier Inc. All rights reserved.)

We conducted an extensive Monte Carlo study of factor-rotation local solutions (LS) in multidimensional, two-parameter logistic (M2PL) item response models. In this study, we simulated more than 19,200 data sets that were drawn from 96 model conditions and performed more than 7.6 million rotations to examine the influence of (a) slope parameter sizes, (b) number of indicators per factor (trait), (c) probabilities of cross-loadings, (d) factor correlation sizes, (e) model approximation error, and (f) sample sizes on the local solution rates of the oblimin and (oblique) geomin rotation algorithms. To accommodate these design variables, we extended the standard M2PL model to include correlated major factors and uncorrelated minor factors (to represent model error). Our results showed that both rotation methods converged to LS under some conditions with geomin producing the highest local solution rates across many models. Our results also showed that, for identical item response patterns, rotation LS can produce different latent trait estimates with different levels of measurement precision (as indexed by the conditional standard error of measurement). Follow-up analyses revealed that when rotation algorithms converged to multiple solutions, quantitative indices of structural fit, such as numerical measures of simple structure, will often misidentify the rotation that is closest in mean-squared error to the factor pattern (or item-slope pattern) of the data-generating model., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Static well plates remain the gold standard to study viral infections in vitro, but they cannot accurately mimic dynamic viral infections as they occur in the human body. Therefore, we established a dynamic cell culture platform, based on centrifugal microfluidics, to study viral infections in perfusion. To do so, we used human primary periodontal dental ligament (PDL) cells and herpes simplex virus-1 (HSV-1) as a case study. By microscopy, we confirmed that the PDL cells efficiently attached and grew in the chip. Successful dynamic viral infection of perfused PDL cells was monitored using fluorescent imaging and RT-qPCR-based experiments. Remarkably, viral infection in flow resulted in a gradient of HSV-1-infected cells gradually decreasing from the cell culture chamber entrance towards its end. The perfusion of acyclovir in the chip prevented HSV-1 spreading, demonstrating the usefulness of such a platform for monitoring the effects of antiviral drugs. In addition, the innate antiviral response of PDL cells, measured by interferon gene expression, increased significantly over time in conventional static conditions compared to the perfusion model. These results provide evidence suggesting that dynamic viral infections differ from conventional static infections, which highlights the need for more physiologically relevant in vitro models to study viral infections.

Purpose: Revumenib, an oral, small molecule inhibitor of the menin-lysine methyltransferase 2A (KMT2A) interaction, showed promising efficacy and safety in a phase I study of heavily pretreated patients with KMT2A -rearranged ( KMT2Ar ) acute leukemia. Here, we evaluated the activity of revumenib in individuals with relapsed/refractory (R/R) KMT2Ar acute leukemia., Methods: AUGMENT-101 is a phase I/II, open-label, dose-escalation and expansion study of revumenib conducted across 22 clinical sites in five countries (ClinicalTrials.gov identifier: NCT04065399). We report results from the phase II, registration-enabling portion. Individuals age ≥30 days with R/R KMT2Ar acute leukemia or with AML and nucleophosmin 1 ( NPM1 ) mutation were enrolled. Revumenib was administered once every 12 hours, at 163 mg (95 mg/m 2 if weight <40 kg) with a strong cytochrome P450 inhibitor, in 28-day cycles. The primary end points were the rate of complete remission (CR) or CR with partial hematologic recovery (CR + CRh) and safety. At a prespecified interim analysis, safety was assessed in all KMT2Ar treated patients; efficacy was assessed in those with centrally confirmed KMT2Ar . The separate NPM1 cohort of the trial is ongoing., Results: From October 1, 2021, to July 24, 2023, N = 94 patients (median [range] age, 37 [1.3-75] years) were treated. Grade ≥3 adverse events included febrile neutropenia (37.2%), differentiation syndrome (16.0%), and QTc prolongation (13.8%). In the efficacy-evaluable patients (n = 57), the CR + CRh rate was 22.8% (95% CI, 12.7 to 35.8), exceeding the null hypothesis of 10% ( P = .0036). Overall response rate was 63.2% (95% CI, 49.3 to 75.6), with 15 of 22 patients (68.2%) having no detectable residual disease., Conclusion: Revumenib led to high remission rates with a predictable safety profile in R/R KMT2Ar acute leukemia. To our knowledge, this trial represents the largest evaluation of a targeted therapy for these patients.

Novel Gram-positive, catalase-negative, α-haemolytic cocci were isolated from breast milk samples of healthy mothers living in Hanoi, Vietnam. The 16S rRNA gene sequences of these strains varied by 0-2 nucleotide polymorphisms. The 16S rRNA gene sequence of one strain, designated as BME SL 6.1 T , showed the highest similarity to those of Streptococcus salivarius NCTC 8618 T (99.4 %), Streptococcus vestibularis ATCC 49124 T (99.4 %), and Streptococcus thermophilus ATCC 19258 T (99.3 %) in the salivarius group. Whole genome sequencing was performed on three selected strains. Phylogeny based on 631 core genes clustered the three strains into the salivarius group, and the strains were clearly distinct from the other species in this group. The average nucleotide identity (ANI) value of strain BME SL 6.1 T exhibited the highest identity with S. salivarius NCTC 8618 T (88.4 %), followed by S. vestibularis ATCC 49124 T (88.3 %) and S. thermophilus ATCC 19258 T (87.4 %). The ANI and digital DNA-DNA hybridization values between strain BME SL 6.1 T and other species were below the cut-off value (95 and 70 %, respectively), indicating that it represents a novel species of the genus Streptococcus . The strains were able to produce α-galactosidase and acid from raffinose and melibiose. Therefore, we propose to assign the strains to a new species of the genus Streptococcus as Streptococcus raffinosi sp. nov. The type strain is BME SL 6.1 T (=VTCC 12812 T =NBRC 116368 T ).

Background: Subclinical pulmonary tuberculosis, which presents without recognisable symptoms, is frequently detected in community screening. However, the disease category is poorly clinically defined. We explored the prevalence of subclinical pulmonary tuberculosis according to different case definitions., Methods: We did a one-stage individual participant data meta-analysis of nationally representative surveys that were conducted in countries with high incidence of tuberculosis between 2007 and 2020, that reported the prevalence of pulmonary tuberculosis based on chest x-ray and symptom screening in participants aged 15 years and older. Screening and diagnostic criteria were standardised across the surveys, and tuberculosis was defined by positive Mycobacterium tuberculosis sputum culture. We estimated proportions of subclinical tuberculosis for three case definitions: no persistent cough (ie, duration ≥2 weeks), no cough at all, and no symptoms (ie, absence of cough, fever, chest pain, night sweats, and weight loss), both unadjusted and adjusted for false-negative chest x-rays and uninterpretable culture results., Findings: We identified 34 surveys, of which 31 were eligible. Individual participant data were obtained and included for 12 surveys (620 682 participants) across eight countries in Africa and four in Asia. Data on 602 863 participants were analysed, of whom 1944 had tuberculosis. The unadjusted proportion of subclinical tuberculosis was 59·1% (n=1149/1944; 95% CI 55·8-62·3) for no persistent cough and 39·8% (773/1944; 36·6-43·0) for no cough of any duration. The adjusted proportions were 82·8% (95% CI 78·6-86·6) for no persistent cough and 62·5% (56·6-68·7) for no cough at all. In a subset of four surveys, the proportion of participants with tuberculosis but without any symptoms was 20·3% (n=111/547; 95% CI 15·5-25·1) before adjustment and 27·7% (95% CI 21·0-36·4) after adjustment. Tuberculosis without cough, irrespective of its duration, was more frequent among women (no persistent cough: adjusted odds ratio 0·79, 95% CI 0·63-0·97; no cough: adjusted odds ratio 0·76, 95% CI 0·62-0·93). Among participants with tuberculosis, 29·1% (95% CI 25·2-33·3) of those without persistent cough and 23·1% (18·8-27·4) of those without any cough had positive smear examinations., Interpretation: The majority of people in the community who have pulmonary tuberculosis do not report cough, a quarter report no tuberculosis-suggestive symptoms at all, and a quarter of those not reporting any cough have positive sputum smears, suggesting infectiousness. In high-incidence settings, subclinical tuberculosis could contribute considerably to the tuberculosis burden and to Mycobacterium tuberculosis transmission., Funding: Mr Willem Bakhuys Roozeboom Foundation., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 World Health Organization. Published by Elsevier Ltd. All rights reserved. Published by Elsevier Ltd.. All rights reserved.)

Introduction and Importance: Os odontoideum is a rare condition commonly associated with atlantoaxial instability (AAI) and leading to atlantoaxial dislocation. The incidence of Os odontoideum is higher in patients with Down syndrome. Similar to odontoid fractures, atlantoaxial dislocation in patients with Os odontoideum can result in neurological deficits, disability, and even mortality., Case Presentation: We present two cases of Os odontoideum accompanied by Down syndrome. Both patients were hospitalized due to progressive tetraparesis after falls several months prior. Upon examination, the patients exhibited myelopathy and were unable to walk or stand. MRI revealed spinal stenosis at the C1-C2 level due to atlantoaxial dislocation. C1-C2 fixation using Harms' technique was performed in both cases. One case experienced a complication involving instrument failure, necessitating revision surgery., Clinical Discussion: Due to the characteristics of transverse ligament laxity, low muscle tone, excessive joint flexibility, and cognitive impairment, children with both Down syndrome and Os odontoideum are at a high risk of disability and even mortality from spinal cord injury. Most authors recommend surgical management when patients exhibit atlantoaxial instability. Additional factors such as low bone density, cognitive impairment, and a high head-to-body ratio may increase the risk of surgical instrument failure and nonunion postoperatively in patients with Down syndrome., Conclusion: Os odontoideum is a cause of AAI in patients with DS. Indication of surgery in the presence of AAI helps to resolve neurological injury and prevent further deterioration. The use of a cervical collar is considered to prevent instrument failure postoperatively., Competing Interests: Declaration of competing interest No potential conflict of interest relevant to this article was reported., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Despite advances in understanding the genetic abnormalities in myeloproliferative neoplasms (MPN) and the development of JAK2 inhibitors, there is an urgent need to devise new treatment strategies, particularly for patients with triple-negative (TN) myelofibrosis (MF) who lack mutations in the JAK2 kinase pathway and have very poor clinical outcomes. Here we report that MYC copy number gain and increased MYC expression frequently occur in TN-MF and that MYC-directed activation of S100A9, an alarmin protein that plays pivotal roles in inflammation and innate immunity, is necessary and sufficient to drive development and progression of MF. Notably, the MYC-S100A9 circuit provokes a complex network of inflammatory signaling that involves numerous hematopoietic cell types in the bone marrow microenvironment. Accordingly, genetic ablation of S100A9 or treatment with small molecules targeting the MYC-S100A9 pathway effectively ameliorates MF phenotypes, highlighting the MYC-alarmin axis as a novel therapeutic vulnerability for this subgroup of MPNs. Significance: This study establishes that MYC expression is increased in TN-MPNs via trisomy 8, that a MYC-S100A9 circuit manifest in these cases is sufficient to provoke myelofibrosis and inflammation in diverse hematopoietic cell types in the BM niche, and that the MYC-S100A9 circuit is targetable in TN-MPNs., (©2024 American Association for Cancer Research.)

Acute myeloid leukemia (AML) is a type of blood cancer with diverse genetic variations and DNA methylation alterations. By studying the interaction of gene mutations, expression, and DNA methylation, we aimed to gain valuable insights into the processes that lead to block differentiation in AML. We analyzed TCGA-LAML data (173 samples) with RNA sequencing and DNA methylation arrays, comparing FLT3 mutant (48) and wild-type (125) cases. We conducted differential gene expression analysis using cBioPortal, identified DNA methylation differences with ChAMP tool, and correlated them with gene expression changes. Gene set enrichment analysis (g:Profiler) revealed significant biological processes and pathways. ShinyGo and GeneCards were used to find potential transcription factors and their binding sites among significant genes. We found significant differentially expressed genes (DEGs) negatively correlated with their most significant methylation probes (Pearson correlation coefficient of -0.49, P-value <0.001) between FLT3 mutant and wild-type groups. Moreover, our exploration of 450 k CpG sites uncovered a global hypo-methylated status in 168 DEGs. Notably, these methylation changes were enriched in the promoter regions of Homebox superfamily gene, which are crucial in transcriptional-regulating pathways in blood cancer. Furthermore, in FLT3 mutant AML patient samples, we observed overexpress of WT1, a transcription factor known to bind homeobox gene family. This finding suggests a potential mechanism by which WT1 recruits TET2 to demethylate specific genomic regions. Integrating gene expression and DNA methylation analyses shed light on the impact of FLT3 mutations on cancer cell development and differentiation, supporting a two-hit model in AML. This research advances understanding of AML and fosters targeted therapeutic strategy development., (© The Author(s) 2024. Published by Oxford University Press.)