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Langerhans cell histiocytosis(LCH)and Langerhans cell sarcoma(LCS)are characterized by clone proliferation of Langerhans-type cells, which may occur concurrently or sequentially with T-cell acute lymphoblastic leukemia (T-ALL) and other Lymphoid neoplasms. A 15-year old female patient diagnosed with T-ALL developed LCH involving multiple systems during maintenance chemotherapy of T-AL. After treated with chemotherapy with improved result, the patient showed progression of the illness and refractory to the second-line treatment. We found c.G35A (p.G12D)mutation in the KRAS gene and used the targeted drug Trametinib for treatment. The treatment proved effective, leading to partial remission within a week. Three months after Trametinib treatment, the patient developed new lymphadenopathy. Biopsy revealed the existence of LCS. The disease progressed quickly, and the patient died 7 days after diagnosis of LCS. The case of patients with T-ALL then developing LCH and LCS sequentially is extraordinarily rare. The causes of the case is unclear and may be related to cell transdifferentiation, clonal evolution, and chemotherapy. Targeted drugs can contain this disease for a short time.

A novel series of 2-(3-fluoro-4-nitrophenoxy)-N-phenylacetamide compounds were designed, synthesized and in vitro assessed for their antitubercular activities by a microdilution method. All the novel derivatives exerted potent or moderate active against M. tuberculosis H37Rv, with MIC values ranging from 4 to 64 μg/mL. The most potent derivative 3m showed an identical MIC value of 4 μg/mL for both M. tuberculosis H37Rv and rifampin-resistant M. tuberculosis 261. It demonstrated no inhibitory effects against six different tumor cell lines by a MTT assay and had a good safety profile in a vero cell line, providing a good lead for subsequent optimization in search of novel affordable antitubercular agents.

A series of N-3-substituted 7-aminopyrido[2,3-d]pyrimidin-6-carbonitrile derivatives was readily synthesized and their anti-proliferative activities on five types of tumor cells were evaluated through a cell-based phenotypic screening approach. Compound 3k was found to be potent on human colon cancer SW620 cells with an IC50 value of 12.5 mM. Structural optimization of compound 3k led to compound 4a with improved anti-proliferative potency on SW620 cells with an IC50 value of 6.9 mM. Further cell-cycle analyses suggested that compound 4a induced apoptosis of SW620 cells in a concentration-dependent manner.

In the title compound, C13H10FNO5S, the dihedral angle between the benzene rings is 47.63 (14)°. In the crystal, π–π stacking occurs between nearly parallel benzene rings of adjacent molecules, the centroid–centroid distance being 3.7806 (16) Å. Weak intermolecular C—H...O hydrogen bonding is also present in the crystal structure.

Abstract Objective The aim of this study was to describe the time series of broad-spectrum antibiotic utilisation and incidence of antibiotic-resistant organisms during the implementation of antimicrobial stewardship programmes (ASP) in Singapore. Methods An observational study was conducted using data from 2011 to 2020 in seven acute-care public hospitals. We applied joinpoint regressions to investigate changes in antibiotic utilisation rate and incidence density of antibiotic-resistant organisms. Results Across the seven hospitals, quarterly broad-spectrum antibiotic utilisation rate remained stable. Half-yearly incidence density of antibiotic-resistant organisms with two joinpoints at first half (H1) of 2012 and second half (H2) of 2014 decreased significantly in the second and third period with a half-yearly percentage change (HPC) of -2.9% and − 0.5%, respectively. Across the five hospitals with complete data, half-yearly broad-spectrum antibiotic utilisation rate with one joinpoint decreased significantly from H1 of 2011 to H2 of 2018 (HPC − 4.0%) and H2 of 2018 to H2 2020 (HPC − 0.5%). Incidence density of antibiotic-resistant organisms decreased significantly in the two joinpoint periods from H1 of 2012 to H2 of 2014 (HPC − 2.7%) and H2 of 2014 to H2 of 2020 (HPC − 1.0%). Ceftriaxone with one joinpoint decreased significantly from H1 of 2011 to H1 of 2014 (HPC − 6.0%) and H1 of 2014 to H2 of 2020 (HPC − 1.8%) and ceftriaxone-resistant E. coli and K. pneumoniae decreased significantly in later periods, from H2 of 2016 to H2 of 2020 (HPC − 2.5%) and H1 of 2012 to H2 of 2015 (HPC − 4.6%) respectively. Anti-pseudomonal antibiotics with one joinpoint decreased significantly from H1 of 2011 to H2 of 2014 (HPC − 4.5%) and H2 of 2014 to H2 of 2020 (HPC − 0.8%) and that of quinolones with one joinpoint at H1 of 2015 decreased significantly in the first period. C. difficile with one joinpoint increased significantly from H1 of 2011 to H1 of 2015 (HPC 3.9%) and decreased significantly from H1 of 2015 to H2 of 2020 (HPC − 4.9%). Conclusions In the five hospitals with complete data, decrease in broad-spectrum antibiotic utilisation rate was followed by decrease in incidence density of antibiotic-resistant organisms. ASP should continue to be nationally funded as a key measure to combat antimicrobial resistance in acute care hospitals.

PurposeCompare results obtained using infrared two-photon microperimetry (2PM-IR) with conventional visual function tests in healthy subjects of varying ages with and without simulated media opacities.MethodsSubjects from two separate cohort studies completed cone contrast threshold (CCT) testing, conventional microperimetry, visible light microperimetry from a novel device (2PM-Vis), and infrared two-photon microperimetry. The first cohort study, which consisted of six healthy volunteers (23 to 29 years of age), evaluated the effects of simulated media opacities on visual performance testing. Subjects underwent testing on four visual function devices nine separate times under the following conditions: no filter, red filter, green filter, blue filter, light brown filter, dark brown filter, polarized black filter (0° rotation), and polarized black filter (90° rotation). Subjects subsequently performed 2PM-IR and 2PM-Vis testing without a filter in the mydriatic state. The second cohort study evaluated the effect of age on visual test performance in 42 healthy subjects split between two groups (ages 20-40 years and 60-80 years).ResultsRetinal sensitivity measured by 2PM-IR demonstrated lower variability than all other devices relying on visible spectrum stimuli. Retinal sensitivity decreased proportionally with the transmittance of light through each filter. CCT scores and retinal sensitivity decreased with age in all testing modalities. Visible spectrum testing modalities demonstrated larger test result differences between young and old patient cohorts; this difference was inversely proportional to the wavelength of the visual function test.Conclusions2PM-IR mitigates media opacities that may mask small differences in retinal sensitivity when tested with conventional visual function testing devices.Translational relevanceConventional visual function tests that emit visible light may not detect differences in retinal function during the early stages of age-related diseases due to the confounding effects of cataracts. Infrared light, which has greater transmittance through ocular tissue, may reliably quantify retinal sensitivity and thereby detect degenerative changes early on.

IntroductionSurgical treatment is increasingly the treatment of choice in cancer patients with epidural spinal cord compression and spinal instability. There has also been an evolution in surgical treatment with the advent of minimally invasive surgical (MIS) techniques and separation surgery. This paper aims to investigate the changes in epidemiology, surgical technique, outcomes and complications in the last 17 years in a tertiary referral center in Singapore.MethodsThis is a retrospective study of 383 patients with surgically treated spinal metastases treated between January 2005 to January 2022. Patients were divided into 3 groups, patients treated between 2005 – 2010, 2011-2016, and 2017- 2021. Demographic, oncological, surgical, patient outcome and survival data were collected. Statistical analysis with univariate analysis was performed to compare the groups.ResultsThere was an increase in surgical treatment (87 vs 105 vs 191). Lung, Breast and prostate cancer were the most common tumor types respectively. There was a significant increase in MIS(p

PurposeTo evaluate effects of age and simulated and real cataractous changes on color vision as measured by the high-definition cone contrast test (CCT).MethodsTwenty-four healthy volunteers from two cohort studies performed CCT using best-corrected visual acuity, filters, mydriasis, and pinhole correction. Retrospective cross-sectional study of patients seen in eye clinics evaluated the relationship between age and color vision, and age and lens status in 355 eyes. Last, 25 subjects underwent CCT before and after cataract surgery.ResultsCCT scores were most reliable in the nonmydriatic condition without pinhole correction. Progressively dense brown filters produced small decreases in S-cone sensitivity. Linear regression analysis of phakic subjects showed a decline for all cone classes with age. Rate of decline was greater for S-cones (slope = -1.09; 95% confidence interval [CI], -1.30 to 0.86) than M-cones (slope = -0.80; 95% CI, -1.03 to -0.58) and L-cones (slope = -0.66; 95% CI, -0.88 to -0.44). CCT scores increased for S-cones but reduced for L- and M-cones in pseudophakic subjects compared with phakic patients. CCT scores after cataract surgery increased for S-cones, M-cones, and L-cones by 33.0 (95% CI, 8.6 to 57.4), 24.9 (95% CI, 3.8 to 46.0), and 22.0 (95% CI, -3.2 to 47.3), respectively.ConclusionsCCT assessment allows for clinically practical quantitation of color and contrast vision improvement after cataract surgery and aging patients who note poor vision despite good visual acuity.Translational relevanceCCT testing, which quantifies hereditary and acquired color deficiency, can also quantify the degree of cataract severity and, combined with other parameters, can provide more precise guidance for cataract extraction to optimize patient care.

Physics-informed neural network (PINN) architectures are recent developments that can act as surrogate models for fluid dynamics in order to reduce computational costs. PINNs make use of deep neural networks, where the Navier-Stokes equation and freestream boundary conditions are used as losses of the neural network; hence, no simulation or experimental data in the training of the PINN is required. Here, the formulation of PINN for fluid dynamics is demonstrated and critical factors influencing the PINN design are discussed through a low Reynolds number flow over a cylinder. The PINN architecture showed the greatest improvement to the accuracy of results from the increase in the number of layers, followed by the increase in the number of points in the point cloud. Increasing the number of nodes per hidden layer brings about the smallest improvement in performance. In general, PINN is much more efficient than computational fluid dynamics (CFD) in terms of memory resource usage, with PINN requiring 5–10 times less memory. The tradeoff for this advantage is that it requires longer computational time, with PINN requiring approximately 3 times more than that of CFD. In essence, this paper demonstrates the direct formulation of PINN without the need for data, alongside hyperparameter design and comparison of computational requirements.

Abstract Background Early diagnosis is crucial in securing optimal outcomes in the HIV care cascade. Recent HIV infection (RHI) serves as an indicator of early detection in the course of HIV infection. Surveillance of RHI is important in uncovering at-risk groups in which HIV transmission is ongoing. The study objectives are to estimate the proportion of RHI among persons newly-diagnosed in 2013–2017, and to elucidate epidemiological factors associated with RHI in Singapore. Methods As part of the National HIV Molecular Surveillance Programme, residual plasma samples of treatment-naïve HIV-1 positive individuals were tested using the biotinylated peptide-capture enzyme immunoassay with a cutoff of normalized optical density ≤ 0.8 for evidence of RHI. A recent infection testing algorithm was applied for the classification of RHI. We identified risk factors associated with RHI using logistic regression analyses. Results A total of 701 newly-diagnosed HIV-infected persons were included in the study. The median age at HIV diagnosis was 38 years (interquartile range, 28–51). The majority were men (94.2%), and sexual route was the predominant mode of HIV transmission (98.3%). Overall, 133/701 (19.0, 95% confidence interval [CI] 16.2–22.0%) were classified as RHI. The proportions of RHI in 2015 (31.1%) and 2017 (31.0%) were significantly higher than in 2014 (11.2%). A significantly higher proportion of men having sex with men (23.4, 95% CI 19.6–27.6%) had RHI compared with heterosexual men (11.1, 95% CI 7.6–15.9%). Independent factors associated with RHI were: age 15–24 years (adjusted odds ratio [aOR] 4.18, 95% CI 1.69–10.31) compared with ≥55 years; HIV diagnosis in 2015 (aOR 2.36, 95% CI 1.25–4.46) and 2017 (aOR 2.52, 95% CI 1.32–4.80) compared with 2013–2014; detection via voluntary testing (aOR 1.91, 95% CI 1.07–3.43) compared with medical care; and self-reported history of HIV test(s) prior to diagnosis (aOR 1.72, 95% CI 1.06–2.81). Conclusion Although there appears to be an increasing trend towards early diagnosis, persons with RHI remain a minority in Singapore. The strong associations observed between modifiable behaviors (voluntary testing and HIV testing history) and RHI highlight the importance of increasing the accessibility to HIV testing for at-risk groups.

COVID-19 infection or vaccination is rarely associated with arterial occlusive disease of the extremities. The surgical department of a hospital in Johor, Malaysia, recorded a significant increase in the number of COVID-19-related acute limb ischaemia when the rates of COVID-19 were high both locally and internationally. The clinical presentation and management of acute limb ischaemia associated with COVID-19 infection or vaccination are largely underreported in Johor. Herein, we report a case series of 12 patients managed with strategies ranging from purely anticoagulation to catheter-directed thrombolysis and surgical embolectomy. This case series describes the clinical presentation, risk profiles, treatment approaches and limb outcomes of the patients. The amputation rate was high in view of unfavourable factors, including delayed presentation, high-risk factors and severe COVID-19. Three cases of potential COVID-19 vaccine-related acute limb ischaemia were included. COVID-19-related acute limb ischaemia can be minimised with heightened alert, preemptive optimisation with proper hydration and consideration for early prophylactic anticoagulation in high-risk cases.

Objective: Abnormal liver tests have been associated with worse clinical outcomes in patients infected with COVID-19. This retrospective observational study from Singapore aims to elucidate simple clinical predictors of abnormal alanine aminotransferase (ALT) in COVID-19 infections. Design: 717 patients hospitalised with COVID-19 at the National Centre for Infectious Diseases (NCID), Singapore, from 23 January–15 April 2020 were screened, of which 163 patients with baseline normal alanine transferase (ALT) and at least two subsequent ALTs performed were included in the final analysis. Information on baseline demographics, clinical characteristics and biochemical laboratory tests were collected. Results: 30.7% of patients developed abnormal ALT. They were more likely to be older (60 vs. 55, p = 0.022) and have comorbidities of hyperlipidaemia and hypertension. The multivariate logistic regression showed that R-factor ≥1 on admission (adjusted odds ratio (aOR) 3.13, 95% Confidence Interval (CI) 1.41–6.95) and hypoxia (aOR 3.54, 95% CI 1.29–9.69) were independent risk factors for developing abnormal ALT. The patients who developed abnormal ALT also ran a more severe course of illness with a greater proportion needing supplementary oxygen (58% vs. 18.6%, p < 0.0005), admission to the Intensive Care Unit (ICU)/High Dependency Unit (HDU) (32% vs. 11.5%, p = 0.003) and intubation (20% vs. 2.7%, p < 0.0005). There was no difference in death rate between the two groups. Conclusions: Liver injury is associated with poor clinical outcomes in patients with COVID-19. R-factor ≥1 on admission and hypoxia are independent simple clinical predictors for developing abnormal ALT in COVID-19.

Tropical urban greenhouses are prone to heat trapping due to higher daily temperatures compared to temperate climates, and a high energy cost is required to maintain optimal growth conditions. Lanthanide-based nanoparticles are known for their capability of performing upconversion, a process where lower energy photons are absorbed and converted to a single photon of higher energy. These upconversion nanoparticles (UCNPs) possess the innate ability to convert infrared energy to visible light, thereby facilitating efficient heat removal while simultaneously providing upconverted visible light. Consequently, the incorporation of such material into greenhouse façades presents an attractive zero-energy alternative to commonly used greenhouse cooling technologies. In this study, NaYF4:Yb3+/Er3+ UCNPs were synthesized and coated onto a simulated greenhouse enclosure with Pak Choi plants to observe the effect of such a film coating on actual crop growth. A reduction of the interior temperature, increased sunlight diffusion, and improved crop yield were demonstrated in this work, showing promising results for future urban greenhouse façade applications. [ABSTRACT FROM AUTHOR]

Background We aimed to analyze the clinical characteristics of peripheral Epstein-Barr virus (EBV)-infected lymphocyte subtypes in children with chronic active EBV infection (CAEBV). Methods The levels of peripheral EBV infection of CD4+ T cells, CD8+ T cells, and CD56+ natural killer (NK) cells were determined by flow cytometry and quantitative polymerase chain reaction (qPCR) in patients with CAEBV from July 2017 to July 2022. Results In total, 112 children with CAEBV were evaluated. Of these, CD4+ type, CD8+ type, and CD56+ type were defined in 44, 21, and 47 patients, respectively. Patients with CD8+ T-cell type had a significantly higher frequency of rash, while hepatomegaly was more common in patients with CD4+ T-cell type. Generally, patients with CD8+ T-cell type had the lowest overall survival rate (P =.017). Patients treated with chemotherapy and hematopoietic stem cell transplantation (HSCT) had a better prognosis (P =.001). In multivariate analysis, rash, hemophagocytic lymphohistiocytosis, CD8+ T-cell type, and no decrease of plasma EBV-DNA after treatment were independent indicators of poor prognosis (P =.002,.024,.022, and.012, respectively). Conclusions In children with CAEBV, rash was more frequent in patients with CD8+ T-cell type, whereas patients with CD4+ T-cell type were more likely to develop hepatomegaly. Patients with CD8+ T-cell type had a poor prognosis despite receiving chemotherapy or further HSCT. [ABSTRACT FROM AUTHOR]