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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 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.)

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.)

Coronaviruses have exceptionally large RNA genomes and employ multiprotein replication/transcription complexes to orchestrate specific steps of viral RNA genome replication and expression. Most of these processes involve viral cis-acting RNA elements that are engaged in vital RNA-RNA and/or RNA-protein interactions. Over the past years, a large number of studies provided interesting new insight into the structures and, to a lesser extent, functions of specific RNA elements for representative coronaviruses, and there is evidence to suggest that (a majority of) these RNA elements are conserved across genetically divergent coronavirus genera. It is becoming increasingly clear that at least some of these elements do not function in isolation but operate through complex and highly dynamic RNA-RNA interactions. This article reviews structural and functional aspects of cis-acting RNA elements conserved in alpha- and betacoronavirus 5'- and 3'-terminal genome regions, focusing on their critical roles in viral RNA synthesis and gene expression., 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 Ltd.. All rights reserved.)

There is an urgent need for rapid, non-sputum point-of-care diagnostics to detect tuberculosis. This prospective trial in seven high tuberculosis burden countries evaluated the diagnostic accuracy of the point-of-care urine-based lipoarabinomannan assay FUJIFILM SILVAMP TB LAM (FujiLAM) among inpatients and outpatients living with HIV. Diagnostic performance of FujiLAM was assessed against a mycobacterial reference standard (sputum culture, blood culture, and Xpert Ultra from urine and sputum at enrollment, and additional sputum culture ≤7 days from enrollment), an extended mycobacterial reference standard (eMRS), and a composite reference standard including clinical evaluation. Of 1637 participants considered for the analysis, 296 (18%) were tuberculosis positive by eMRS. Median age was 40 years, median CD4 cell count was 369 cells/ul, and 52% were female. Overall FujiLAM sensitivity was 54·4% (95% CI: 48·7-60·0), overall specificity was 85·2% (83·2-87·0) against eMRS. Sensitivity and specificity estimates varied between sites, ranging from 26·5% (95% CI: 17·4%-38·0%) to 73·2% (60·4%-83·0%), and 75·0 (65·0%-82·9%) to 96·5 (92·1%-98·5%), respectively. Post-hoc exploratory analysis identified significant variability in the performance of the six FujiLAM lots used in this study. Lot variability limited interpretation of FujiLAM test performance. Although results with the current version of FujiLAM are too variable for clinical decision-making, the lipoarabinomannan biomarker still holds promise for tuberculosis diagnostics. The trial is registered at clinicaltrials.gov (NCT04089423)., Competing Interests: RS, AM, CMD and MR are or were employed by FIND at the time of the study. FIND is a not-for-profit foundation that supports the evaluation of publicly prioritized tuberculosis assays and the implementation of WHO-approved (guidance and prequalification) assays using donor grants. FIND has product evaluation agreements with several private sector companies that design diagnostics for tuberculosis and other diseases. These agreements strictly define FIND’s independence and neutrality with regard to these private sector companies. TB reports patents in the field of TB detection and is a shareholder of Avelo Inc. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Székely 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.)

Background: Trypoxylon Latreille, 1796 (Hymenoptera, Crabronidae) consists of 633 known species worldwide and the genus is divided into numerous species groups. In Vietnam, 19 species of Trypoxylon have been recorded to date. In this study, a new species, Trypoxylonsicklum Pham and Antropov sp. nov. is described and illustrated from Vinh Phuc Province, Vietnam. The new species is the second member of the Trypoxylonfulvocollare species group. A key to species in the Trypoxylonfulvocollaris group is presented., New Information: Trypoxylonsicklum Pham and Antropov sp. nov., is described as a new species and is the second member of the Trypoxylonfulvocollare species group. A key to species in the Trypoxylonfulvocollaris group is presented., (Phong Huy Pham, Alexander V. Antropov, Hieu Van Nguyen.)

Controlling the access of proteases to cleavable peptides placed at specific locations within macromolecular architectures represents a powerful strategy for biologically responsive materials design. Here, we report the synthesis of peptide-containing bivalent bottlebrush (co)polymers (BBPs) featuring polyethylene glycol (PEG) and 7-amino-4-methylcoumarin (AMC) pendants on each backbone repeat unit. The AMCs are linked via caspase-3-cleavable peptides which, upon enzymatic cleavage, provide a "turn-on" fluorescence signal due to the release of free AMC. Time-dependent fluorscence measurements demonstrate that the caspase-3-induced peptide cleavage and AMC release from BBPs is strongly dependent on the BBP backbone length and the AMC-peptide linker location within the BBP architecture, revealing fundamental insights into the interactions of enzymes with BBPs.

Due to global demand, millions of tons of plastics have been widely consumed, resulting in the widespread entry of vast amounts of microplastic particles into the environment. The presence of microplastics (MPs) in water supplies, including bottled water, has undergone systematic review, assessing the potential impacts of MPs on humans through exposure assessment. The main challenges associated with current technologies lie in their ability to effectively treat and completely remove MPs from drinking and supply water. While the risks posed by MPs upon entering the human body have not yet been fully revealed, there is a predicted certainty of negative impacts. This review encompasses a range of current technologies, spanning from basic to advanced treatments and varying in scale. However, given the frequent detection of MPs in drinking and bottled water, it becomes imperative to implement comprehensive management strategies to address this issue effectively. Consequently, integrating current technologies with management options such as life-cycle assessment, circular economy principles, and machine learning is crucial to eliminating this pervasive problem., 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 Elsevier B.V. All rights reserved.)

Reliable large-scale cell detection and segmentation is the fundamental first step to understanding biological processes in the brain. The ability to phenotype cells at scale can accelerate preclinical drug evaluation and system-level brain histology studies. The impressive advances in deep learning offer a practical solution to cell image detection and segmentation. Unfortunately, categorizing cells and delineating their boundaries for training deep networks is an expensive process that requires skilled biologists. This paper presents a novel self-supervised Dual-Loss Adaptive Masked Autoencoder (DAMA) for learning rich features from multiplexed immunofluorescence brain images. DAMA's objective function minimizes the conditional entropy in pixel-level reconstruction and feature-level regression. Unlike existing self-supervised learning methods based on a random image masking strategy, DAMA employs a novel adaptive mask sampling strategy to maximize mutual information and effectively learn brain cell data. To the best of our knowledge, this is the first effort to develop a self-supervised learning method for multiplexed immunofluorescence brain images. Our extensive experiments demonstrate that DAMA features enable superior cell detection, segmentation, and classification performance without requiring many annotations. In addition, to examine the generalizability of DAMA, we also experimented on TissueNet, a multiplexed imaging dataset comprised of two-channel fluorescence images from six distinct tissue types, captured using six different imaging platforms. Our code is publicly available at https://github.com/hula-ai/DAMA., Competing Interests: Declaration of competing interest There is no Conflict of Interest., (Copyright © 2024. Published by Elsevier B.V.)

Polymer-protein bioconjugation offers a powerful strategy to alter the physical properties of proteins, and various synthetic polymer compositions and architectures have been investigated for this purpose. Nevertheless, conjugation of molecular bottlebrush polymers (BPs) to proteins remains an unsolved challenge due to the large size of BPs and a general lack of methods to transform the chain ends of BPs into functional groups suitable for bioconjugation. Here, we present a strategy to address this challenge in the context of BPs prepared by "graft-through" ring-opening metathesis polymerization (ROMP), one of the most powerful methods for BP synthesis. Quenching ROMP of PEGylated norbornene macromonomers with an activated enyne terminator facilitates the transformation of the BP Ru alkylidene chain ends into Pd oxidative addition complexes (OACs) for facile bioconjugation. This strategy is shown to be effective for the synthesis of two BP-protein conjugates (albumin and ERG), setting the stage for a new class of BP-protein conjugates for future therapeutic and imaging applications.

Background and Objectives: Little is known regarding the cost-effectiveness of lecanemab (Leqembi), a monoclonal antibody approved by the US Food and Drug Administration in January 2023 for the treatment of mild cognitive impairment (MCI) or mild dementia due to Alzheimer disease (AD). This study aims to quantify the cost-effectiveness of lecanemab and how it varies based on the accuracy of AD testing and individuals' APOE ε4 status., Methods: Seven alternative test-treat-target strategies defined by combinations of testing approaches (PET, CSF, or plasma assay), treatment choices (standard of care [SoC] alone or lecanemab in addition to SoC), and targeting strategies (targeting APOE ε4 noncarriers or heterozygous patients or not) were compared. A hybrid decision tree-Markov cohort model was constructed with 5 states: (1) MCI (Clinical Dementia Rating-Sum of Boxes [CDR-SB] 0-4.5); (2) mild dementia (CDR-SB 4.6-9.5); (3) moderate dementia (CDR-SB 9.6-16); (4) severe dementia (CDR-SB >16); and (5) death. Effectiveness was measured by quality-adjusted life years and costs from third-party and societal perspectives were estimated in 2022 US dollars over a lifetime horizon., Results: Among the 7 test-treat-target strategies, SoC alone was the optimal strategy from a cost-effectiveness perspective. Neither targeted lecanemab treatment nor treatment unrestricted by APOE ε4 genotype was cost-effective vs SoC alone, regardless of the test used to diagnose patients with early-stage AD. However, CSF assay followed by targeted treatment would become cost-effective if lecanemab is priced below $5,100 per year. These results were robust to the accuracy of diagnostic testing and rates of lecanemab discontinuation and adverse events., Discussion: Neither targeted lecanemab treatment nor treatment unrestricted by APOE ε4 genotype is cost-effective vs SoC alone for patients with MCI or mild dementia due to AD. Lecanemab would be cost-effective in some settings if priced below $5,100 per year.

Background: The COVID-19 pandemic has underscored the significance of adopting healthy lifestyles to mitigate the risk of severe outcomes and long-term consequences., Objective: This study focuses on assessing the prevalence and clustering of 5 unhealthy lifestyle behaviors among Vietnamese adults after recovering from COVID-19, with a specific emphasis on sex differences., Methods: The cross-sectional data of 5890 survivors of COVID-19 in Vietnam were analyzed from December 2021 to October 2022. To examine the sex differences in 5 unhealthy lifestyle behaviors (smoking, drinking, unhealthy diet, physical inactivity, and sedentary behavior), the percentages were plotted along with their corresponding 95% CI for each behavior. Latent class analysis was used to identify 2 distinct classes of individuals based on the clustering of these behaviors: the "less unhealthy" group and the "more unhealthy" group. We examined the sociodemographic characteristics associated with each identified class and used logistic regression to investigate the factors related to the "more unhealthy" group., Results: The majority of individuals (male participants: 2432/2447, 99.4% and female participants: 3411/3443, 99.1%) exhibited at least 1 unhealthy behavior, with male participants being more susceptible to multiple unhealthy behaviors. The male-to-female ratio for having a single behavior was 1.003, but it escalated to 25 for individuals displaying all 5 behaviors. Male participants demonstrated a higher prevalence of combining alcohol intake with sedentary behavior (949/2447, 38.8%) or an unhealthy diet (861/2447, 35.2%), whereas female participants tended to exhibit physical inactivity combined with sedentary behavior (1305/3443, 37.9%) or an unhealthy diet (1260/3443, 36.6%). Married male participants had increased odds of falling into the "more unhealthy" group compared to their single counterparts (odds ratio [OR] 1.45, 95% CI 1.14-1.85), while female participants exhibited lower odds (OR 0.65, 95% CI 0.51-0.83). Female participants who are underweight showed a higher likelihood of belonging to the "more unhealthy" group (OR 1.11, 95% CI 0.89-1.39), but this was not observed among male participants (OR 0.6, 95% CI 0.41-0.89). In both sexes, older age, dependent employment, high education, and obesity were associated with higher odds of being in the "more unhealthy" group., Conclusions: The study identified notable sex differences in unhealthy lifestyle behaviors among survivors of COVID-19. Male survivors are more likely to engage in unhealthy behaviors compared to female survivors. These findings emphasize the importance of tailored public health interventions targeting sex-specific unhealthy behaviors. Specifically, addressing unhealthy habits is crucial for promoting post-COVID-19 health and well-being., (©Lan T H Le, Thi Ngoc Anh Hoang, Tan T Nguyen, Tien D Dao, Binh N Do, Khue M Pham, Vinh H Vu, Linh V Pham, Lien T H Nguyen, Hoang C Nguyen, Tuan V Tran, Trung H Nguyen, Anh T Nguyen, Hoan V Nguyen, Phuoc B Nguyen, Hoai T T Nguyen, Thu T M Pham, Thuy T Le, Thao T P Nguyen, Cuong Q Tran, Ha-Linh Quach, Kien T Nguyen, Tuyen Van Duong. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 02.04.2024.)

Pelvic organ prolapse refers to the descent of pelvic floor organs resulting from the weakening of pelvic muscles, fascia and connective tissue. The overall prevalence of pelvic organ prolapse is approximately 41%, including bladder prolapse (25%-34%), uterine prolapse (4%-14%) and rectal prolapse (13%-19%). Various methods are currently employed to repair damaged structures and improve patient symptoms, consequently enhancing their quality of life. This report focuses on a 94-year-old female diagnosed with pelvic organ prolapse, specifically Grade 3 bladder prolapse, Grade 3 uterine prolapse and complete rectal prolapse. A comprehensive surgical treatment was carried out to repair the pelvic organs on all three levels (rectum, uterus and bladder) by combining the Delorme procedure with synthetic graft implants. The surgical outcomes were good, illustrating immediate improvement in symptoms without early complications. A multispeciality approach helps functionally repair pelvic organ prolapse while preserving structural integrity., (Copyright © 2024 Copyright: © 2024 Nigerian Postgraduate Medical Journal.)

Background: There is increasing interest in understanding the impact of non-medical cannabis legalization on use of other substances, especially alcohol. Evidence on whether cannabis is a substitute or complement for alcohol is both mixed and limited. This study provides the first quasi-experimental evidence on the impact of Canada's legalization of non-medical cannabis on beer and spirits sales., Methods: We used the interrupted time series design and monthly data on beer sales between January 2012 and February 2020 and spirits sales between January 2016 and February 2020 across Canada to investigate changes in beer and spirits sales following Canada's cannabis legalization in October 2018. We examined changes in total sales, nationally and in individual provinces, as well as changes in sales of bottled, canned and kegged beer., Results: Canada-wide beer sales fell by 96 hectoliters per 100,000 population (p=0.011) immediately after non-medical cannabis legalization and by 4 hectoliters per 100,000 population (p>0.05) each month thereafter for an average monthly reduction of 136 hectoliters per 100,000 population (p<0.001) post-legalization. However, the legalization was associated with no change in spirits sales. Beer sales reduced in all provinces except the Atlantic provinces. By beer type, the legalization was associated with declines in sales of canned and kegged beer but there was no reduction in sales of bottled beer., Conclusions: Non-medical cannabis legalization was associated with a decline in beer sales in Canada, suggesting substitution of non-medical cannabis for beer. However, there was no change in spirits sales following the legalization., Competing Interests: Declaration of Competing Interest No conflict was declared., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Scabies is a neglected tropical disease and represents a considerable global burden. Although consensus diagnostic criteria for scabies have been recently published, diagnosing scabies infestation remains challenging in clinical practice. We investigated the diagnostic utility of complete blood cell count (CBC) and CBC-derived ratios obtained at diagnosis in a set of 167 patients who are Vietnamese with confirmed scabies. These parameters were compared with those of patients with dermatophytosis (N = 800) and urticaria (N = 2023), two diseases frequent in Vietnam, which can present with similar skin manifestations to scabies and tend to pose a diagnostic challenge in vulnerable populations. Our analysis revealed that white blood cell, monocyte, and eosinophil counts were significantly higher among patients with scabies than the other two diseases. Similarly, the monocyte-to-lymphocyte ratio (MLR) and eosinophil-to-lymphocyte ratio (ELR) were significantly higher among patients with scabies. The optimal cut-off values to distinguish scabies from dermatophytosis and urticaria were 0.094 for ELR (sensitivity: 74.85%, specificity: 70.7%) and 0.295 for MLR (sensitivity: 52.69%, specificity: 73.54%). CBC, ELR, and MLR are low-cost and easily calculated parameters that may be helpful for the diagnosis of scabies.

In response to the increasing number of carbapenem-resistant Enterobacterales (CRE), we investigated carbapenemase-producing Klebsiella pneumoniae and non-K. pneumoniae epidemiology and genetics. We collected 76 clinical Enterobacterales and 4 stool surveillance Escherichia coli isolates resistant to ertapenem or imipenem. Using polymerase chain reaction (PCR) and DNA sequencing, we assessed carbapenemases, extended-spectrum β-lactamases, and AmpC β-lactamases. Molecular typing via pulsed-field gel electrophoresis (PFGE) and conjugation experiments were conducted to examine resistance gene transfer. Among the 80 isolates, 96.2% harbored at least one carbapenemase gene, with bla OXA-48 in 87.5%. KPC-2 and IMP-8 carbapenemases were found in 15.0 and 22.5% of the isolates, respectively, with 27.5% having 2 or more carbapenemase genes. The PFGE analysis revealed the presence of diverse genotypes. PCR-based plasmid replicon typing identified IncA/C as the most prevalent type among K. pneumoniae isolates (26/29), and IncF and IncFIB among E. coli isolates (22/28). Conjugal transfer was successful for plasmids encoding OXA-48, CTX-M-3, CTX-M-14, CMY-2, and other β-lactamases, except the KPC-2 gene. In conclusion, our study highlights high carbapenemase prevalence in CRE, primarily OXA-48. Multiple carbapenemases within strains were common, and PFGE showed diverse patterns in these carbapenem-resistant isolates.

AbstractBackground: Little is known about U.S. healthcare provider views and practices regarding evidence, counseling, and shared decision-making about in-hospital versus out-of-hospital birth settings., Methods: We conducted 19 in-depth, semistructured, qualitative interviews of eight obstetricians, eight midwives, and three pediatricians from across the United States. Interviews explored healthcare providers' interpretation of the current evidence and their personal and professional experiences with childbirth within the existing medical, ethical, and legal context in the United States., Results: Themes emerged concerning risks and benefits, decision-making, and patient-provider power dynamics. Collectively, the narratives illuminated fundamental ideological tensions between in- and out-of-hospital providers arising from divergent assignment of value to described risks and benefits. The majority of physicians focused on U.S.-specific data demonstrating increased neonatal morbidity and mortality associated with delayed access to hospital-based interventions, thereby justifying hospital birth as the standard of care. By contrast, midwives emphasized data demonstrating fewer interventions and superior maternal and neonatal outcomes in high-income European countries, where out-of-hospital birth is more common for low-risk birthing people. A key gap in counseling was revealed, as no interviewees offered anticipatory counseling regarding birth setting options. Providers directly and indirectly illustrated the propensity for asymmetric power relations between birth providers and pregnant people, especially in hospital settings., Conclusions: The narratives highlight the common goal of optimizing maternal and neonatal outcomes despite tensions arising from divergent prioritization of specific maternal and neonatal risks. Our findings suggest opportunities to foster collaboration and optimize outcomes via mutual respect and improved integration of care.

Importance: In March 2020, British Columbia, Canada, became the first jurisdiction globally to launch a large-scale provincewide safer supply policy. The policy allowed individuals with opioid use disorder at high risk of overdose or poisoning to receive pharmaceutical-grade opioids prescribed by a physician or nurse practitioner, but to date, opioid-related outcomes after policy implementation have not been explored., Objective: To investigate the association of British Columbia's Safer Opioid Supply policy with opioid prescribing and opioid-related health outcomes., Design, Setting, and Participants: This cohort study used quarterly province-level data from quarter 1 of 2016 (January 1, 2016) to quarter 1 of 2022 (March 31, 2022), from British Columbia, where the Safer Opioid Supply policy was implemented, and Manitoba and Saskatchewan, where the policy was not implemented (comparison provinces)., Exposure: Safer Opioid Supply policy implemented in British Columbia in March 2020., Main Outcomes and Measures: The main outcomes were rates of prescriptions, claimants, and prescribers of opioids targeted by the Safer Opioid Supply policy (hydromorphone, morphine, oxycodone, and fentanyl); opioid-related poisoning hospitalizations; and deaths from apparent opioid toxicity. Difference-in-differences analysis was used to compare changes in outcomes before and after policy implementation in British Columbia with those in the comparison provinces., Results: The Safer Opioid Supply policy was associated with statistically significant increases in rates of opioid prescriptions (2619.6 per 100 000 population; 95% CI, 1322.1-3917.0 per 100 000 population; P < .001) and claimants (176.4 per 100 000 population; 95% CI, 33.5-319.4 per 100 000 population; P = .02). There was no significant change in prescribers (15.7 per 100 000 population; 95% CI, -0.2 to 31.6 per 100 000 population; P = .053). However, the opioid-related poisoning hospitalization rate increased by 3.2 per 100 000 population (95% CI, 0.9-5.6 per 100 000 population; P = .01) after policy implementation. There were no statistically significant changes in deaths from apparent opioid toxicity (1.6 per 100 000 population; 95% CI, -1.3 to 4.5 per 100 000 population; P = .26)., Conclusions and Relevance: Two years after its launch, the Safer Opioid Supply policy in British Columbia was associated with higher rates of safer supply opioid prescribing but also with a significant increase in opioid-related poisoning hospitalizations. These findings will help inform ongoing debates about this policy not only in British Columbia but also in other jurisdictions that are contemplating it.

Tuberculosis (TB) and non-communicable diseases (NCD) share predisposing risk factors. TB-associated NCD might cluster within households affected with TB requiring shared prevention and care strategies. We conducted an individual participant data meta-analysis of national TB prevalence surveys to determine whether NCD cluster in members of households with TB. We identified eligible surveys that reported at least one NCD or NCD risk factor through the archive maintained by the World Health Organization and searching in Medline and Embase from 1 January 2000 to 10 August 2021, which was updated on 23 March 2023. We compared the prevalence of NCD and their risk factors between people who do not have TB living in households with at least one person with TB (members of households with TB), and members of households without TB. We included 16 surveys (n = 740,815) from Asia and Africa. In a multivariable model adjusted for age and gender, the odds of smoking was higher among members of households with TB (adjusted odds ratio (aOR) 1.23; 95% CI: 1.11-1.38), compared with members of households without TB. The analysis did not find a significant difference in the prevalence of alcohol drinking, diabetes, hypertension, or BMI between members of households with and without TB. Studies evaluating household-wide interventions for smoking to reduce its dual impact on TB and NCD may be warranted. Systematically screening for NCD using objective diagnostic methods is needed to understand the actual burden of NCD and inform comprehensive interventions., Competing Interests: TSo declares a receipt of funding from the Global Fund for conducting the TB prevalence survey in Mongolia. All other authors declare no competing interests., (Copyright: © 2024 Hamada 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.)

Introduction: The literature puts forward a range of challenges of interprofessional education (IPE) related to its planning, initiation, implementation, and especially to IPE assessment. The present study aims to map changes in students' readiness and interprofessional collaboration competence (IPCC) in implementing an innovative IPE module. Potential differences in impact related to the health education programs and IPCC scores resulting from self-, peer-, and tutor assessments will also be analysed., Methods: A pre-post design was adopted. The student's readiness for interprofessional learning was assessed using the Readiness for Interprofessional Learning Scale, and the student's IPCC score was calculated based on self-, peer-, and tutor assessments with the interprofessional collaborator assessment rubric., Results: Students' mean post-test readiness scores and mean post-test IPCC scores were significantly higher than the total and subscales/domain pre-test scores (p<0.01). No significant within-subject differences were observed in students' readiness total or subscale scores when comparing health educational programs. However, significant differences were observed in students' mean total IPCC scores between programs (p<0.01). Significant differences in students' average IPCC scores were found when comparing self-, peer- and tutor assessment scores in six domains (p<0.01). Also, significant correlations between peer and tutor assessment scores were observed (p<0.01)., Conclusion: The IPE module, designed and implemented to focus on patient-centred practice within a primary care context, positively impacted students' readiness and IPCC development. These results offer insights to expand the implementation of the IPE module to all health educational programs., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Nguyen 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.)

Foods and beverages high in free sugars can displace healthier choices and increase the risk of weight gain, dental caries, and noncommunicable diseases. Little is known about the intake of free sugars across early childhood. This study aimed to examine the longitudinal intake from 1 to 5 years of free sugars and identify the independent maternal and child-related predictors of intake in a cohort of Australian children participating in the Study of Mothers' and Infants' Life Events Affecting Oral Health (SMILE). Free sugars intake (FSI) was previously estimated at 1, 2, and 5 years of age, and three distinct FSI trajectories were determined using group-based trajectory modelling analysis. This study utilized multinomial logistic regression to identify the maternal and child-related predictors of the trajectories. The risk of following the 'high and increasing' trajectory of FSI compared to the 'low and fast increasing' trajectory was inversely associated with socio-economic disadvantage (aRRR 0.83; 95% CI 0.75-0.92; p < 0.001), lower for females (aRRR 0.56; 95% CI 0.32-0.98; p = 0.042), and higher in children with two or more older siblings at birth (aRRR 2.32; 95% CI 0.99-5.42; p = 0.052). Differences in trajectories of FSI were evident from an early age and a high trajectory of FSI was associated primarily with socio-economic disadvantage, providing another example of diet quality following a social gradient.

Background: The prevalence of posttraumatic stress disorder (PTSD) has increased, particularly among individuals who have recovered from coronavirus disease 2019 (COVID-19) infection. Health literacy is considered a "social vaccine" that helps people respond effectively to the pandemic. We aimed to investigate the association between long COVID-19 and PTSD, and to examine the modifying role of health literacy in this association., Methods: A cross-sectional study was conducted at 18 hospitals and health centers in Vietnam from December 2021 to October 2022. We recruited 4,463 individuals who had recovered from COVID-19 infection for at least 4 weeks. Participants provided information about their sociodemographics, clinical parameters, health-related behaviors, health literacy (using the 12-item short-form health literacy scale), long COVID-19 symptoms and PTSD (Impact Event Scale-Revised score of 33 or higher). Logistic regression models were used to examine associations and interactions., Results: Out of the study sample, 55.9% had long COVID-19 symptoms, and 49.6% had PTSD. Individuals with long COVID-19 symptoms had a higher likelihood of PTSD (odds ratio [OR], 1.86; 95% confidence interval [CI], 1.63-2.12; p<0.001). Higher health literacy was associated with a lower likelihood of PTSD (OR, 0.98; 95% CI, 0.97-0.99; p=0.001). Compared to those without long COVID-19 symptoms and the lowest health literacy score, those with long COVID-19 symptoms and a 1-point health literacy increment had a 3% lower likelihood of PTSD (OR, 0.97; 95% CI, 0.96-0.99; p=0.001)., Conclusion: Health literacy was found to be a protective factor against PTSD and modified the negative impact of long COVID-19 symptoms on PTSD.

Background: Continuous feeding does not elicit an optimal anabolic response in skeletal muscle but is required for some preterm infants. We reported previously that intermittent intravenous pulses of leucine (Leu; 800 μmol Leu·kg -1 ·h -1 every 4 h) to continuously fed pigs born at term promoted mechanistic target of rapamycin complex 1 (mTORC1) activation and protein synthesis in skeletal muscle., Objectives: The aim was to determine the extent to which intravenous Leu pulses activate mTORC1 and enhance protein synthesis in the skeletal muscle of continuously fed pigs born preterm., Methods: Pigs delivered 10 d preterm was advanced to full oral feeding >4 d and then assigned to 1 of the following 4 treatments for 28 h: 1) ALA (continuous feeding; pulsed with 800 μmol alanine·kg -1 ·h -1 every 4 h; n = 8); 2) L1× (continuous feeding; pulsed with 800 μmol Leu·kg -1 ·h -1 every 4 h; n = 7); 3) L2× (continuous feeding; pulsed with 1600 μmol Leu·kg -1 ·h -1 every 4 h; n = 8); and 4) INT (intermittent feeding every 4 h; supplied with 800 μmol alanine·kg -1 per feeding; n = 7). Muscle protein synthesis rates were determined with L-[ 2 H 5 -ring]Phenylalanine. The activation of insulin, amino acid, and translation initiation signaling pathways were assessed by Western blot., Results: Peak plasma Leu concentrations were 134% and 420% greater in the L2× compared to the L1× and ALA groups, respectively (P < 0.01). Protein synthesis was greater in the L2× than in the ALA and L1× groups in both the longissimus dorsi and gastrocnemius muscles (P < 0.05) but not different from the INT group (P > 0.10). Amino acid signaling upstream and translation initiation signaling downstream of mTORC1 largely corresponded to the differences in protein synthesis., Conclusions: Intravenous Leu pulses potentiate mTORC1 activity and protein synthesis in the skeletal muscles of continuously fed preterm pigs, but the amount required is greater than in pigs born at term., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: As part of its recreational cannabis legalization in October 2018, Canada imposed an excise tax of 10% (or $1 a gram, whichever is higher) on both recreational and medical cannabis. There is little evidence to inform the ongoing debate on whether the legalization had adverse impacts on medical cannabis use. Methods: We used an interrupted time series design and data on medical cannabis shipments (i.e., mail-order deliveries of cannabis from a licensed producer to a patient authorized to obtain medical cannabis) in Canada between quarter 1 of 2014 and quarter 1 of 2020. We examined changes in medical cannabis shipments after Canada's recreational cannabis legalization both across Canada and for each province. As this study used publicly available, province-level aggregate data, ethics approval was not required. Results: Recreational cannabis legalization was associated with significant reductions in medical cannabis use in 7 out of 10 Canadian provinces. Compared with the counterfactual estimated from prelegalization trends, the reduction in quarter 1 of 2020 varied from 500 shipments per 100,000 population (95% CI=312-688 shipments per 100,000 population) or 32% (95% CI=22-43%) in Newfoundland and Labrador to 3,778 shipments per 100,000 population (95% CI=2,972-4,585 shipments per 100,000 population) or 74% (95% CI=68-79%) in Alberta. At the national level, the number of medical cannabis shipments decreased by 823 per 100,000 population (95% CI=725-921 shipments per 100,000 population) or 48% (95% CI=45-52%). Conclusions: Recreational cannabis legalization was associated with reductions in medical cannabis use. Our findings call for policy attention to address possible adverse impacts of recreational cannabis legalization on medical cannabis users.

The male of Okinawepipona yty Nguyen, 2018 is described and illustrated for the first time, together with its genitalia, based on specimens from Y Ty, Lao Cai, Vietnam. In addition, the male genitalia of O. curcipunctura Nguyen & Xu, 2014 is also described for the first time. Based on these descriptions, a discussion is provided regarding the male genitalia of eumenine wasps in general.

Background: Wearable devices have been used extensively both inside and outside of the hospital setting. During the COVID-19 pandemic, in some contexts, there was an increased need to remotely monitor pulse and saturated oxygen for patients due to the lack of staff and bedside monitors., Objective: A prototype of a remote monitoring system using wearable pulse oximeter devices was implemented at the Hospital for Tropical Diseases in Ho Chi Minh City, Vietnam, from August to December 2021. The aim of this work was to support the ongoing implementation of the remote monitoring system., Methods: We used an action learning approach with rapid pragmatic methods, including informal discussions and observations as well as a feedback survey form designed based on the technology acceptance model to assess the use and acceptability of the system. Based on these results, we facilitated a meeting using user-centered design principles to explore user needs and ideas about its development in more detail., Results: In total, 21 users filled in the feedback form. The mean technology acceptance model scores ranged from 3.5 (for perceived ease of use) to 4.4 (for attitude) with behavioral intention (3.8) and perceived usefulness (4.2) scoring in between. Those working as nurses scored higher on perceived usefulness, attitude, and behavioral intention than did physicians. Based on informal discussions, we realized there was a mismatch between how we (ie, the research team) and the ward teams perceived the use and wider purpose of the technology., Conclusions: Designing and implementing the devices to be more nurse-centric from their introduction could have helped to increase their efficiency and use during the complex pandemic period., (©An Phuoc Luu, Truong Thanh Nguyen, Van Thi Cam Cao, Trinh Hoang Diem Ha, Lien Thi Thu Chung, Trung Ngoc Truong, Tung Nguyen Le Nhu, Khoa Bach Dao, Hao Van Nguyen, Phan Nguyen Quoc Khanh, Khanh Thuy Thuy Le, Luu Hoai Bao Tran, Phung Tran Huy Nhat, Duc Minh Tran, Yen Minh Lam, Catherine Louise Thwaites, Jacob Mcknight, Nguyen Van Vinh Chau, Jennifer Ilo Van Nuil, Vietnam ICU Translational Applications Laboratory (VITAL). Originally published in JMIR Human Factors (https://humanfactors.jmir.org), 05.01.2024.)

Importance: While some have argued that cannabis legalization has helped to reduce opioid-related morbidity and mortality in the US, evidence has been mixed. Moreover, existing studies did not account for biases that could arise when policy effects vary over time or across states or when multiple policies are assessed at the same time, as in the case of recreational and medical cannabis legalization., Objective: To quantify changes in opioid prescriptions and opioid overdose deaths associated with recreational and medical cannabis legalization in the US., Design, Setting, and Participants: This quasiexperimental, generalized difference-in-differences analysis used annual state-level data between January 2006 and December 2020 to compare states that legalized recreational or medical cannabis vs those that did not., Intervention: Recreational and medical cannabis law implementation (proxied by recreational and medical cannabis dispensary openings) between 2006 and 2020 across US states., Main Outcomes and Measures: Opioid prescription rates per 100 persons and opioid overdose deaths per 100 000 population based on data from the US Centers for Disease Control and Prevention., Results: Between 2006 and 2020, 13 states legalized recreational cannabis and 23 states legalized medical cannabis. There was no statistically significant association of recreational or medical cannabis laws with opioid prescriptions or overall opioid overdose mortality across the 15-year study period, although the results also suggested a potential reduction in synthetic opioid deaths associated with recreational cannabis laws (4.9 fewer deaths per 100 000 population; 95% CI, -9.49 to -0.30; P = .04). Sensitivity analyses excluding state economic indicators, accounting for additional opioid laws and using alternative ways to code treatment dates yielded substantively similar results, suggesting the absence of statistically significant associations between cannabis laws and the outcomes of interest during the full study period., Conclusions and Relevance: The results of this study suggest that, after accounting for biases due to possible heterogeneous effects and simultaneous assessment of recreational and medical cannabis legalization, the implementation of recreational or medical cannabis laws was not associated with opioid prescriptions or opioid mortality, with the exception of a possible reduction in synthetic opioid deaths associated with recreational cannabis law implementation.

For uncooled infrared cameras based on microbolometers, silicon caps are often utilized to maintain a vacuum inside the packaged bolometer array. To reduce Fresnel reflection losses, anti-reflection coatings are typically applied on both sides of the silicon caps.This work investigates whether black silicon may be used as an alternative to conventional anti-reflective coatings. Reactive ion etching was used to etch the black silicon layer and deep cavities in silicon. The effects of the processed surfaces on optical transmission and image quality were investigated in detail by Fourier transform infrared spectroscopy and with modulated transfer function measurements. The results show that the etched surfaces enable similar transmission to the state-of-the-artanti-reflection coatings in the 8-12 µm range and possibly obtain wider bandwidth transmission up to 24 µm. No degradation in image quality was found when using the processed wafers as windows. These results show that black silicon can be used as an effective anti-reflection layer on silicon caps used in the vacuum packaging of microbolometer arrays.

Introduction: Endogenous endophthalmitis-related Klebsiella pyogenic liver abscess is a rare complication of metastatic infection. In most cases, visual acuity results are often impaired, even blind, and even with aggressive treatment with topical antibiotics, the final results are unsatisfactory. The objective of this study is to retrospectively based on medical records to describe clinical features, risk factors, and visual outcomes of patients with endogenous endophthalmitis-related pyogenic liver abscesses., Methods: We reported a case series of 12 endogenous endophthalmitis-related pyogenic liver abscess patients from March 2021 to 2023. All cases of endogenous endophthalmitis were diagnosed at admission or during the hospital stay., Results: From the medical records of 588 pyogenic liver abscess patients, we found 12 cases of endogenous endophthalmitis with 2.0%. The result showed a mean age of 61.5 ± 12.0 (41-78), diabetes mellitus (7 of 12), right lobe (7 of 12), single abscess (9 of 12), and the mean largest abscess diameter of 5.8 ± 1.7 cm (3.3-9). All patients had ocular symptoms such as eye pain (9 of 12), pus discharge (3 of 12), hypopyon (1 of 12), swollen eyelids (2 of 12), and corneal edema (2 of 12), pyogenic liver abscess before endogenous endophthalmitis (10 of 12), the median interval between endogenous endophthalmitis and pyogenic liver abscess 6.1 ± 1.9 days, ocular symptoms before diagnosis endogenous endophthalmitis 4.4 ± 2.3 days. All affected eyes were injected intravitreously with ceftazidime, amikacin, and vancomycin. Two patients underwent evisceration., Conclusions: Endogenous endophthalmitis has permanent morbidity, reducing visual acuity, poor quality of life, and lacks the warning signs, so it is essential for early detection of symptoms and referral to ophthalmologists., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Background: Individuals with bacteriologically confirmed pulmonary tuberculosis (TB) disease who do not report symptoms (subclinical TB) represent around half of all prevalent cases of TB, yet their contribution to Mycobacterium tuberculosis ( Mtb ) transmission is unknown, especially compared to individuals who report symptoms at the time of diagnosis (clinical TB). Relative infectiousness can be approximated by cumulative infections in household contacts, but such data are rare., Methods: We reviewed the literature to identify studies where surveys of Mtb infection were linked to population surveys of TB disease. We collated individual-level data on representative populations for analysis and used literature on the relative durations of subclinical and clinical TB to estimate relative infectiousness through a cumulative hazard model, accounting for sputum-smear status. Relative prevalence of subclinical and clinical disease in high-burden settings was used to estimate the contribution of subclinical TB to global Mtb transmission., Results: We collated data on 414 index cases and 789 household contacts from three prevalence surveys (Bangladesh, the Philippines, and Viet Nam) and one case-finding trial in Viet Nam. The odds ratio for infection in a household with a clinical versus subclinical index case (irrespective of sputum smear status) was 1.2 (0.6-2.3, 95% confidence interval). Adjusting for duration of disease, we found a per-unit-time infectiousness of subclinical TB relative to clinical TB of 1.93 (0.62-6.18, 95% prediction interval [PrI]). Fourteen countries across Asia and Africa provided data on relative prevalence of subclinical and clinical TB, suggesting an estimated 68% (27-92%, 95% PrI) of global transmission is from subclinical TB., Conclusions: Our results suggest that subclinical TB contributes substantially to transmission and needs to be diagnosed and treated for effective progress towards TB elimination., Funding: JCE, KCH, ASR, NS, and RH have received funding from the European Research Council (ERC) under the Horizon 2020 research and innovation programme (ERC Starting Grant No. 757699) KCH is also supported by UK FCDO (Leaving no-one behind: transforming gendered pathways to health for TB). This research has been partially funded by UK aid from the UK government (to KCH); however, the views expressed do not necessarily reflect the UK government's official policies. PJD was supported by a fellowship from the UK Medical Research Council (MR/P022081/1); this UK-funded award is part of the EDCTP2 programme supported by the European Union. RGW is funded by the Wellcome Trust (218261/Z/19/Z), NIH (1R01AI147321-01), EDTCP (RIA208D-2505B), UK MRC (CCF17-7779 via SET Bloomsbury), ESRC (ES/P008011/1), BMGF (OPP1084276, OPP1135288 and INV-001754), and the WHO (2020/985800-0)., Competing Interests: JE, SB, BF, FG, KH, SH, IL, Fv, HN, HN, MQ, AR, ET, RW, KZ, FC, RH No competing interests declared, PD has received consultancy fees from WHO (TB burden estimation) and participates as chair of SAB for NIHR grant on TBI screening. The author has no other competing interests to declare, GM acts as President of the International Union Against TB & Lung Disease. The author has no other competing interests to declare, IO has received grants from National TB Program Cambodia, WHO and DFAT (Australia) and has received consulting fees from WHO Myanmar Office. The author is on the Board of the Directors, UNION IUATLD and WHO’s Global Task Force on TB Impact Measurement. The author has no other competing interests to declare, NS received a grant from the Bill and Melinda Gates Foundation and owns stock/stock options in Sanofi Aventis Pharma LTD. The author has no other competing interests to declare, (© 2023, Emery et al.)

Prior studies have successfully used manganese oxides to facilitate the transformation of tetracycline in aqueous solution. To further understand the kinetic and the transformation pathway of tetracycline via birnessite (δ-MnO 2 ) under different conditions, experiments were conducted at pH levels of 3, 6, and 9 in the presence or absence of Aldrich humic acid (ADHA). Tetracycline removal followed the pseudo-second-order reaction model in all investigated cases, and the removal efficiency (g mg -1 h -1 ) followed the following trend: pH 3 (0.45/0.27) > pH 6 (0.036/0.087) > pH 9 (0.036/0.103) in the absence/presence of ADHA. Liquid chromatography-mass spectrometry/mass spectrometry results identified five main transformation products at m/z 495, 477, 493, 459, and 415, produced by the transformation reactions, including hydration, oxidation, desaturation, and oxy reduction. Notably, in the presence of ADHA at pH 3, products with higher toxicity secondary (m/z 477 and 495) were reduced, while less toxicity products (m/z 459 and 415) were enhanced. The experiments utilizing tetracycline and δ-MnO 2 with varied humic acids (HA) revealed that HA with high polar organic carbon groups, such as O-alkyl, exhibited higher removal efficiency at pH 6. This research offers the first comprehensive insights into the pathway transformations of tetracycline via δ-MnO 2 under different pH conditions and HA types. For further understanding, future work should investigate the binding of HA, TTC, and/or Mn 2+ and the oxidation capacity of MnO 2 after the reaction to clarify Mn 2+ elution mechanisms., 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 © 2023 Elsevier Ltd. All rights reserved.)

Monitoring and prevention of the formation of disinfection by-products (DBPs) is paramount in drinking water treatment plants (DWTP) to ensure human health safety. This review provides an overview of how fluorescence techniques are developed to predict DBP formation and to evaluate the reduction of fluorescence components and DBPs following individual DWTP processes. Evidence has shown that common DBPs, nitrogenous DBPs and specific emerging DBPs exhibit positive linear relationships with terrestrial, anthropogenic, tryptophan-like, and eutrophic humic-like fluorescence. Due to the interrelationships of both regulated and emerging DBP types with fluorescence components, the limitations arise when attempting to predict emerging DBPs solely through linear relationships. Monitoring the reduction of DBP precursors after each treatment process can be achieved by studying the relationship between fluorescence components and DBPs. During the coagulation process, highest reduction rates are observed for terrestrial humic-like fluorescence. Advanced treatments such as granular, powdered, silver-impregnated activated carbon, magnetic ion exchange resins, and reverse osmosis, have revealed a significant reduction of fluorescent DBP precursors, ranging from 53% to 100%. During chlorination, the reduction rate follows the order: terrestrial humic-like > microbial humic-like > protein/tryptophan-like fluorescence. This review provides insights into the reduction of fluorescence signatures following individual DWTP processes, which offers information regarding DBP formation. These insights could assist in optimizing the treatment process to more effectively manage DBP formation. For the identification of emerging DBP generation, the utilization of advanced models is imperative to precisely predict emerging DBPs and to more accurately trace DBP precursors within DWTPs., 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 © 2023 Elsevier Ltd. All rights reserved.)

Background and Objective: The Oxford Classification for IgA nephropathy is the most successful example of an evidence-based nephropathology classification system. The aim of our study was to replicate the glomerular components of Oxford scoring with an end-to-end deep learning pipeline that involves automatic glomerular segmentation followed by classification for mesangial hypercellularity (M), endocapillary hypercellularity (E), segmental sclerosis (S) and active crescents (C)., Methods: A total number of 1056 periodic acid-Schiff (PAS) whole slide images (WSIs), coming from 386 kidney biopsies, were annotated. Several detection models for glomeruli, based on the Mask R-CNN architecture, were trained on 587 WSIs, validated on 161 WSIs, and tested on 127 WSIs. For the development of segmentation models, 20,529 glomeruli were annotated, of which 16,571 as training and 3958 as validation set. The test set of the segmentation module comprised of 2948 glomeruli. For the Oxford classification, 6206 expert-annotated glomeruli from 308 PAS WSIs were labelled for M, E, S, C and split into a training set of 4298 glomeruli from 207 WSIs, and a test set of 1908 glomeruli. We chose the best-performing models to construct an end-to-end pipeline, which we named MESCnn (MESC classification by neural network), for the glomerular Oxford classification of WSIs., Results: Instance segmentation yielded excellent results with an AP50 ranging between 78.2-80.1 % (79.4 ± 0.7 %) on the validation and 75.1-77.7 % (76.5 ± 0.9 %) on the test set. The aggregated Jaccard Index was between 73.4-75.9 % (75.0 ± 0.8 %) on the validation and 69.1-73.4 % (72.2 ± 1.4 %) on the test set. At granular glomerular level, Oxford Classification was best replicated for M with EfficientNetV2-L with a mean ROC-AUC of 90.2 % and a mean precision/recall area under the curve (PR-AUC) of 81.8 %, best for E with MobileNetV2 (ROC-AUC 94.7 %) and ResNet50 (PR-AUC 75.8 %), best for S with EfficientNetV2-M (mean ROC-AUC 92.7 %, mean PR-AUC 87.7 %), best for C with EfficientNetV2-L (ROC-AUC 92.3 %) and EfficientNetV2-S (PR-AUC 54.7 %). At biopsy-level, correlation between expert and deep learning labels fulfilled the demands of the Oxford Classification., Conclusion: We designed an end-to-end pipeline for glomerular Oxford Classification on both a granular glomerular and an entire biopsy level. Both the glomerular segmentation and the classification modules are freely available for further development to the renal medicine community., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)