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Justin B Hellman, Michele C Lim, Karen Y Leung, Cameron M Blount, Glenn Yiu Department of Ophthalmology & Vision Sciences, University of California, Davis Medical Center, Sacramento, CA, USA Purpose: To determine the financial and clinical impact of conversion from International Classification of Disease, 9th revision (ICD-9) to ICD-10 coding.Design: Retrospective, database study.Materials and methods: Monthly billing and coding data from 44,564 billable patient encounters at an academic ophthalmology practice were analyzed by subspecialty in the 1-year periods before (October 1, 2014, to September 30, 2015) and after (October 1, 2015, to September 30, 2016) conversion from ICD-9 to ICD-10.Main outcomes and measures: Primary outcome measures were payments per visit, relative value units per visit, number of visits, and percentage of high-level visits; secondary measures were denials due to coding errors, charges denied due to coding errors, and percentage of unspecified codes used as a primary diagnosis code.Results: Conversion to ICD-10 did not significantly impact payments per visit ($306.56±$56.50 vs $321.43±$38.12, P=0.42), relative value units per visit (7.15±0.56 vs 7.13±0.84, P=0.95), mean volume of visits (1,887.08±375.02 vs 1,863.83±189.81, P=0.71), or percentage of high-level visits (29.7%±4.9%, 548 of 1,881 vs 30.0%±1.7%, 558 of 1,864, P=0.81). For every 100 visits, the number of coding-related denials increased from 0.98±0.60 to 1.84±0.31 (P

Francina EM Dams,2 KY Esther Leung,1 Pieter HM van der Valk,2 Marc CJM Kock,2 Jeroen Bosman,1 Sjoerd P Niehof1 1Medical Physics and Technology, 2Department of Radiology, Albert Schweitzer Hospital, Dordrecht, The Netherlands Background: To inform cost-effective decisions in purchasing new medical liquid crystal displays, we compared the image quality in displays made by three manufacturers. Methods: We recruited 19 radiologists and residents to compare the image quality of four liquid crystal displays, including 3-megapixel Barco®, Eizo®, and NEC® displays and a 6-megapixel Barco display. The evaluators were blinded to the manufacturers' names. Technical assessments were based on acceptance criteria and test patterns proposed by the American Association of Physicists in Medicine. Radiological assessments were performed on images from the American Association of Physicists in Medicine Task Group 18. They included X-ray images of the thorax, knee, and breast, a computed tomographic image of the thorax, and a magnetic resonance image of the brain. Image quality was scored on an analog scale (range 0–10). Statistical analysis was performed with repeated-measures analysis of variance. Results: The Barco 3-megapixel display passed all acceptance criteria. The Eizo and NEC displays passed the acceptance criteria, except for the darkest pixel value in the grayscale display function. The Barco 6-megapixel display failed criteria for the maximum luminance response and the veiling glare. Mean radiological assessment scores were 7.8±1.1 (Barco 3-megapixel), 7.8±1.2 (Eizo), 8.1±1.0 (NEC), and 8.1±1.0 (Barco 6-megapixel). No significant differences were found between displays. Conclusion: According to the tested criteria, all the displays had comparable image quality; however, there was a three-fold difference in price between the most and least expensive displays. Keywords: data display, humans, radiographic image enhancement, user-computer interface, liquid crystals

We have measured the muon flux and production rate of muon-induced neutrons at a depth of 611 m water equivalent. Our apparatus comprises three layers of crossed plastic scintillator hodoscopes for tracking the incident cosmic-ray muons and 760 L of a gadolinium-doped liquid scintillator for producing and detecting neutrons. The vertical muon intensity was measured to be Iμ=(5.7±0.6)×10-6 cm-2 s-1 sr-1. The yield of muon-induced neutrons in the liquid scintillator was determined to be Yn=(1.19±0.08(stat)±0.21(syst))×10-4 neutrons/(μ·g·cm-2). A fit to the recently measured neutron yields at different depths gave a mean muon energy dependence of 0.76±0.03 for liquid-scintillator targets.

This Letter reports a measurement of the flux and energy spectrum of electron antineutrinos from six 2.9 GWth nuclear reactors with six detectors deployed in two near (effective baselines 512 and 561 m) and one far (1579 m) underground experimental halls in the Daya Bay experiment. Using 217 days of data, 296 721 and 41 589 inverse β decay (IBD) candidates were detected in the near and far halls, respectively. The measured IBD yield is (1.55±0.04) ×10(-18)  cm(2) GW(-1) day(-1) or (5.92±0.14) ×10(-43)  cm(2) fission(-1). This flux measurement is consistent with previous short-baseline reactor antineutrino experiments and is 0.946±0.022 (0.991±0.023) relative to the flux predicted with the Huber-Mueller (ILL-Vogel) fissile antineutrino model. The measured IBD positron energy spectrum deviates from both spectral predictions by more than 2σ over the full energy range with a local significance of up to ∼4σ between 4-6 MeV. A reactor antineutrino spectrum of IBD reactions is extracted from the measured positron energy spectrum for model-independent predictions.

We developed a highly sensitive, reliable and portable automatic system (H3) to monitor the radon concentration of the underground experimental halls of the Daya Bay Reactor Neutrino Experiment. H3 is able to measure radon concentration with a statistical error less than 10% in a 1-h measurement of dehumidified air (R.H. 5% at 25°C) with radon concentration as low as 50 Bq/m3. This is achieved by using a large radon progeny collection chamber, semiconductor α-particle detector with high energy resolution, improved electronics and software. The integrated radon monitoring system is highly customizable to operate in different run modes at scheduled times and can be controlled remotely to sample radon in ambient air or in water from the water pools where the antineutrino detectors are being housed. The radon monitoring system has been running in the three experimental halls of the Daya Bay Reactor Neutrino Experiment since November 2013.

We report a new measurement of electron antineutrino disappearance using the fully constructed Daya Bay Reactor Neutrino Experiment. The final two of eight antineutrino detectors were installed in the summer of 2012. Including the 404 days of data collected from October 2012 to November 2013 resulted in a total exposure of 6.9×10^{5} GW_{th}  ton days, a 3.6 times increase over our previous results. Improvements in energy calibration limited variations between detectors to 0.2%. Removal of six ^{241}Am-^{13}C radioactive calibration sources reduced the background by a factor of 2 for the detectors in the experimental hall furthest from the reactors. Direct prediction of the antineutrino signal in the far detectors based on the measurements in the near detectors explicitly minimized the dependence of the measurement on models of reactor antineutrino emission. The uncertainties in our estimates of sin^{2}2θ_{13} and |Δm_{ee}^{2}| were halved as a result of these improvements. An analysis of the relative antineutrino rates and energy spectra between detectors gave sin^{2}2θ_{13}=0.084±0.005 and |Δm_{ee}^{2}|=(2.42±0.11)×10^{-3}  eV^{2} in the three-neutrino framework.

The Daya Bay Reactor Neutrino Experiment was designed to achieve a sensitivity on the value of sin22θ13 to better than 0.01 at 90% CL. The experiment consists of eight antineutrino detectors installed underground at different baselines from six nuclear reactors. With data collected with six antineutrino detectors for 55 days, Daya Bay announced the discovery of a non-zero value for sin22θ13 with a significance of 5.2 standard deviations in March 2012. The most recent analysis with 139 days of data acquired in a six-detector configuration yields sin22θ13=0.089±0.010(stat.)±0.005(syst.), which is the most precise measurement of sin22θ13 to date. © 2013.

We report an improved measurement of the neutrino mixing angle θ13 from the Daya Bay Reactor Neutrino Experiment. We exclude a zero value for sin22θ13 with a significance of 7.7 standard deviations. Electron antineutrinos from six reactors of 2.9 GW th were detected in six antineutrino detectors deployed in two near (flux-weighted baselines of 470 m and 576 m) and one far (1648 m) underground experimental halls. Using 139 days of data, 28909 (205308) electron antineutrino candidates were detected at the far hall (near halls). The ratio of the observed to the expected number of antineutrinos assuming no oscillations at the far hall is 0.944±0.007(stat.)±0.003(syst.). An analysis of the relative rates in six detectors finds sin22θ13=0. 089±0.010(stat.)±0.005(syst.) in a three-neutrino framework. © 2013 Chinese Physical Society and the Institute of High Energy Physics of the Chinese Academy of Sciences and the Institute of Modern Physics of the Chinese Academy of Sciences and IOP Publishing Ltd.

OBJECTIVES: To determine haematological parameters in fetuses affected by homozygous [alpha](0)-thalassemia. METHODS: This was a cross-sectional retrospective study reviewing 546 blood samples (268 fetal and 278 neonatal cord) being collected between 1993 and 2006, from 12 weeks' gestation onwards for any indication, including the prenatal diagnosis of homozygous [alpha](0)-thalassemia, other haematological disorders, hydrops or aneuploidy. The proportion of haemoglobin (Hb) fractions was determined by electrophoresis of haemolysate on cellulose acetate in all samples. RESULTS: There were significant differences in the haematological parameters between homozygous [alpha](0)-thalassemia (n = 183) and control (n = 363) which were either heterozygous [alpha](0)-thalassemia (alpha thalassemia trait) or normal. In homozygous [alpha](0)-thalassemia, the median Hb level, proportion of Hb Bart's ([gamma](4)) and Hb Portland 1((2)[gamma](2)) were 6.4 g/dL, 77.5% and 22.5%, respectively. While the Hb level and the proportion of Hb Bart's increased significantly with gestation, the proportion of Hb Portland 1 decreased. The Hb level contributed by Hb Portland 1 remained around 1.4 g/dL throughout gestation. The proportion of mild, moderate and severe anaemia in the affected fetuses was 27.5, 32.7 and 39.8%, respectively. There was no significant difference in these proportions across different gestation (P = 0.231). There were no differences in the haematological parameters between hydropic and non-hydropic fetuses. CONCLUSION: Although the degree of anaemia is mild in around one-quarter of the affected fetuses, the contribution by Hb Portland 1 ((2)[gamma](2)) to the Hb level was very low throughout gestation, and the affected fetuses may therefore be at risk for hypoxia. Copyright © 2010 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Objectives: To compare XI VOCAL (eXtended Imaging Virtual Organ Computer-aided AnaLysis) for three-dimensional (3D) ultrasound volumetry of the placenta and of phantom objects with a rotational method using VOCAL and with the multiplanar method. Methods: We acquired 3D volume datasets from 32 fetuses at 11-14 weeks' gestation. Placental volume was calculated twice by each of two observers using XI VOCAL (with 5, 10, 15 and 20 slices), multiplanar (1-mm interval) and VOCAL (with 12 degrees, 18 degrees and 30 degrees rotation) methods. In addition, validity was assessed using the in-vitro setting with three phantom objects of known volume. Results: Both inter- and intraobserver reliabilities were very high for all three methods. There was no systematic bias between any two methods except between XI VOCAL (10 slices) and the multiplanar (1-mm interval) method, with a smaller volume using the former method. The limits of agreement were wide between any two of the three methods. In the in-vitro setting, there was a trend towards less valid measurements with the XI VOCAL technique and fewer slices. With the same number of steps, measurements made with VOCAL (12 degrees and 18 degrees) were more valid than were those made with XI VOCAL (15 and 10 slices, respectively). Conclusion: XI VOCAL cannot be used interchangeably with VOCAL or multiplanar techniques in measuring placental volume at 11-14 weeks' gestation. [ABSTRACT FROM AUTHOR]

Objective: To compare the predictive values of three ultrasonographic parameters: placental thickness (PT), fetal cardiothoracic ratio (CTR) and middle cerebral artery peak systolic velocity (MCA-PSV), alone or in combination, in pregnancies affected by homozygous alpha(0)-thalassemia at 12-20 weeks' gestation. Methods: Pregnant women at risk of carrying a fetus affected by homozygous alpha(0)-thalassemia were studied from 1995 to 2006 using serial ultrasonography at 12-15 weeks, 16-20 weeks and 30 weeks' gestation. We measured CTR and PT from 1995, and MCA-PSV as well from 1997. An invasive prenatal test was offered if cardiomegaly with or without placentomegaly was detected but the MCA-PSV results were used only retrospectively for analysis. Results: Of a total of 777 at-risk fetuses studied, 138 (17.8%) were affected by homozygous alpha(0)-thalassemia. At 12-15 weeks' gestation, 598 ultrasound examinations were performed. CTR was better than both PT and MCA-PSV in the prediction of affected pregnancies. The highest sensitivity (98.3%) was achieved by the combination of CTR and/or MCA-PSV at a false-positive rate of 15.8%. At 16-20 weeks' gestation, 410 ultrasound examinations were performed, 121 of which were at the patient's first visit and 289 of which were at a follow-up visit. Both CTR and MCA-PSV predicted the affected pregnancies equally well. The sensitivity of CTR was 100.0%, but the false-positive rate was 5.2%. In contrast, the false-positive rate of MCA-PSV alone was 1.4% and that of the combination of CTR and MCA-PSV was 0%, although their sensitivities were less than 65%. Conclusions: The data suggest that adding MCA-PSV to CTR in the prediction of homozygous alpha(0)-thalassemia can increase the sensitivity at 12-15 weeks and decrease the false-positive rate at 16-20 weeks' gestation. [ABSTRACT FROM AUTHOR]

Objectives: To compare the new XI VOCAL (eXtended Imaging Virtual Organ Computer-aided Analysis) for three-dimensional (3D) ultrasound measurement of fetal volume with the conventional multiplanar technique and a rotational method using VOCAL. Methods: We acquired 3D volume datasets from 30 fetuses at 11-14 weeks of gestation using a commercially available ultrasound system. Fetal volume was calculated using XI VOCAL (with 5, 10, 15 and 20 slices), multiplanar (1-mm interval) and VOCAL (with 12 degrees, 18 degrees and 30 degrees rotation) techniques. The level of agreement for interobserver and intraobserver variability was determined and evaluated for all methods and reliability was assessed. Results: Fetal volume measurements obtained using XI VOCAL (10 slices) showed good correlation with those obtained using VOCAL (18 degrees) (r = 0.940, P = 0.076; intraclass correlation coefficient (ICC), 0.962 (95% CI, 0.920-0.982), P = 0.182), and XI VOCAL (15 slices) showed good correlation with VOCAL (12 degrees ) (r = 0.961, P = 0.092; ICC, 0.979 (95% CI, 0.957-0.990), P = 0.190). The mean difference between paired measurements by the XI VOCAL (10 slices) and VOCAL (18 degrees ) methods was 1.00 mL, while that by the XI VOCAL (15 slices) and VOCAL (12 degrees) methods was 0.90 mL. 95% limits of agreement were - 2.80 to 4.80 between XI VOCAL (10 slices) and VOCAL (18 degrees) and - 1.90 to 3.70 between XI VOCAL (15 slices) and VOCAL (12 degrees). There was a small difference in the time required to complete the fetal volume measurement between XI VOCAL and VOCAL when a similar number of slices or rotational steps was used (P < 0.05), XI VOCAL taking less time. Conclusion: XI VOCAL (with 10, 15 and 20 slices) can be used interchangeably with the multiplanar technique (1-mm interval) for the measurement of fetal volume. XI VOCAL (10 slices) and VOCAL (18 degrees) can be used interchangeably, as can XI VOCAL (15 slices) and VOCAL (12 degrees), for the measurement of fetal volume. [ABSTRACT FROM AUTHOR]

The mortality and hospitalization rate by COVID-19 dropped significantly currently, but its seasonal outbreaks make antiviral treatment still vital. The mortality and hospitazation rate by COVID-19 dropped significantly currently, but its seasonal ourbreaks make antiviral treatment still vital. In our study, syrian golden hamsters were treated with molnupiravir and interferons (IFNs) after SARS-CoV-2 infection. Their weight changes, pathological changes, virus replication and inflammation levels were evaluated. In the IFNs single treatment, only IFN-α group reduced viral load (p < 0.05) and virus titer in hamster lungs. The TNF-α expression decreased significantly in both IFNs treatment at 2dpi. Histological and immunofluorescence results showed lung damage in the IFNs groups were milder at 4dpi. In the molnupiravir/IFN-α combination treatment, weight loss and virus replication in lung were significantly decreased in the mono-molnupiravir group and combination group (p < 0.05), the expression of IL-6, TNF-α, IL-1β and MIP-1α also decreased significantly (p < 0.05), but the combination treatment was not more effective than the mono-molnupiravir treatment. Histological and immunofluorescence results showed the lung damage and inflammation in mono-molnupiravir and combination groups were milder. In summary, IFNs treatment had anti-inflammatory effect against SARS-CoV-2, only IFN-α showed a weak antiviral effect. Molnupiravir/IFN-α combination treatment was effective against SARS-CoV-2 but was not superior to mono-molnupiravir treatment. IFN-α could be considered for immunocompromised patients to stimulate and activate early immune responses., (© 2024 Wiley Periodicals LLC.)

The emergence and dissemination of antibiotic resistance genes (ARGs) in the ecosystem are global public health concerns. One Health emphasizes the interconnectivity between different habitats and seeks to optimize animal, human, and environmental health. However, information on the dissemination of antibiotic resistance genes (ARGs) within complex microbiomes in natural habitats is scarce. We investigated the prevalence of antibiotic resistant bacteria (ARB) and the spread of ARGs in intensive bullfrog (Rana catesbeiana) farms in the Shantou area of China. Antibiotic susceptibilities of 361 strains, combined with microbiome analyses, revealed Escherichia coli, Edwardsiella tarda, Citrobacter and Klebsiella sp. as prevalent multidrug resistant bacteria on these farms. Whole genome sequencing of 95 ARB identified 250 large plasmids that harbored a wide range of ARGs. Plasmid sequences and sediment metagenomes revealed an abundance of tetA, sul1, and aph(3″)-Ib ARGs. Notably, antibiotic resistance (against 15 antibiotics) highly correlated with plasmid-borne rather than chromosome-borne ARGs. Based on sequence similarities, most plasmids (62%) fell into 32 distinct groups, indicating a potential for horizontal plasmid transfer (HPT) within the frog farm microbiome. HPT was confirmed in inter- and intra-species conjugation experiments. Furthermore, identical mobile ARGs, flanked by mobile genetic elements (MGEs), were found in different locations on the same plasmid, or on different plasmids residing in the same or different hosts. Our results suggest a synergy between MGEs and HPT to facilitate ARGs dissemination in frog farms. Mining public databases retrieved similar plasmids from different bacterial species found in other environmental niches globally. Our findings underscore the importance of HPT in mediating the spread of ARGs in frog farms and other microbiomes of the ecosystem., 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 Author(s). Published by Elsevier Ltd.. All rights reserved.)

Non-Ketotic Hyperglycinemia (NKH) is a rare inborn error of metabolism caused by impaired function of the glycine cleavage system (GCS) and characterised by accumulation of glycine in body fluids and tissues. NKH is an autosomal recessive condition and the majority of affected individuals carry mutations in GLDC (glycine decarboxylase). Current treatments for NKH have limited effect and are not curative. As a monogenic condition with known genetic causation, NKH is potentially amenable to gene therapy. An AAV9-based expression vector was designed to target sites of GCS activity. Using a ubiquitous promoter to drive expression of a GFP reporter, transduction of liver and brain was confirmed following intra-venous and/or intra-cerebroventricular administration to neonatal mice. Using the same capsid and promoter with transgenes to express mouse or human GLDC, vectors were then tested in GLDC-deficient mice that provide a model of NKH. GLDC-deficient mice exhibited elevated plasma glycine concentration and accumulation of glycine in liver and brain tissues as previously observed. Moreover, the folate profile indicated suppression of folate one‑carbon metabolism (FOCM) in brain tissue, as found at embryonic stages, and reduced abundance of FOCM metabolites including betaine and choline. Neonatal administration of vector achieved reinstatement of GLDC mRNA and protein expression in GLDC-deficient mice. Treated GLDC-deficient mice showed significant lowering of plasma glycine, confirming functionality of vector expressed protein. AAV9-GLDC treatment also led to lowering of brain tissue glycine, and normalisation of the folate profile indicating restoration of glycine-derived one‑carbon supply. These findings support the hypothesis that AAV-mediated gene therapy may offer potential in treatment of NKH., Competing Interests: Declaration of competing interest None., (Copyright © 2023. Published by Elsevier Inc.)

Background: The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has lasted for three years. Coinfection with seasonal influenza may occur resulting in more severe diseases. The interaction between these two viruses for infection and the effect of antiviral treatment remains unclear., Methods: A SARS-CoV-2 and influenza H1N1 coinfection model on Calu-3 cell line was established, upon which the simultaneous and sequential coinfection was evaluated by comparing the viral load. The efficacy of molnupiravir and baloxavir against individual virus and coinfection were also studied., Results: The replication of SARS-CoV-2 was significantly interfered when the influenza virus was infected simultaneously or in advance (p < 0.05). On the contrary, the replication of the influenza virus was not affected by the SARS-CoV-2. Molnupiravir monotherapy had significant inhibitory effect on SARS-CoV-2 when the concentration reached to 6.25 μM but did not show any significant anti-influenza activity. Baloxavir was effective against influenza within the dosage range and showed significant effect of anti-SARS-CoV-2 at 16 μM. In the treatment of coinfection, molnupiravir had significant effect for SARS-CoV-2 from 6.25 μM to 100 μM and inhibited H1N1 at 100 μM (p < 0.05). The tested dosage range of baloxavir can inhibit H1N1 significantly (p < 0.05), while at the highest concentration of baloxavir did not further inhibit SARS-CoV-2, and the replication of SARS-CoV-2 significantly increased in lower concentrations. Combination treatment can effectively inhibit influenza H1N1 and SARS-CoV-2 replication during coinfection. Compared with molnupiravir or baloxavir monotherapy, combination therapy was more effective in less dosage to inhibit the replication of both viruses., Conclusions: In coinfection, the replication of SARS-CoV-2 would be interfered by influenza H1N1. Compared with molnupiravir or baloxavir monotherapy, treatment with a combination of molnupiravir and baloxavir should be considered for early treatment in patients with SARS-CoV-2 and influenza coinfection., 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 B.V. All rights reserved.)

Maternal nutrition contributes to gene-environment interactions that influence susceptibility to common congenital anomalies such as neural tube defects (NTDs). Supplemental myo-inositol (MI) can prevent NTDs in some mouse models and shows potential for prevention of human NTDs. We investigated effects of maternal MI intake on embryonic MI status and metabolism in curly tail mice, which are genetically predisposed to NTDs that are inositol-responsive but folic acid resistant. Dietary MI deficiency caused diminished MI in maternal plasma and embryos, showing that de novo synthesis is insufficient to maintain MI levels in either adult or embryonic mice. Under normal maternal dietary conditions, curly tail embryos that developed cranial NTDs had significantly lower MI content than unaffected embryos, revealing an association between diminished MI status and failure of cranial neurulation. Expression of inositol-3-phosphate synthase 1, required for inositol biosynthesis, was less abundant in the cranial neural tube than at other axial levels. Supplemental MI or d-chiro-inositol (DCI) have previously been found to prevent NTDs in curly tail embryos. Here, we investigated the metabolic effects of MI and DCI treatments by mass spectrometry-based metabolome analysis. Among inositol-responsive metabolites, we noted a disproportionate effect on nucleotides, especially purines. We also found altered proportions of 5-methyltetrahydrolate and tetrahydrofolate in MI-treated embryos suggesting altered folate metabolism. Treatment with nucleotides or the one-carbon donor formate has also been found to prevent NTDs in curly tail embryos. Together, these findings suggest that the protective effect of inositol may be mediated through the enhanced supply of nucleotides during neural tube closure., (© 2024 The Author(s). The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.)

Objective: There is a lack of reliable and valid evidence-based practice (EBP) measures for physiotherapy students. This study validated EBP-student (EBP-S) measures for physiotherapy students., Methods: EBP measures developed from previous research were cross-culturally validated for use by physiotherapy students. The adapted EBP-S consisted of six measures: use of EBP, EBP activities, EBP knowledge, self-efficacy for EBP, attitudes towards EBP, and perceptions of the teaching and assessment of EBP in the curriculum. The final version was completed by physiotherapy students (n = 335). The psychometric properties for each EBP-S measure were estimated, including construct validity using Rasch model, internal consistency reliability using person separation index (PSI), test-retest reliability using intraclass correlation coefficient (ICC), and differential item functioning (DIF)., Results: Two formative measures (use of EBP and EBP activities) were only linguistically modified for use with students. A Rasch model was applied to the other four reflective measures. For knowledge, 55% (6/11) items fit the Rasch model with chi-square fit statistic (χ2) = 34.46, p = 0.08; PSI = 0.85. For self-efficacy, 89% (8/9) items fit the Rasch model with χ2 = 25.11, p = 0.80; PSI = 0.89. For attitudes, 62% (8/13) items fit the Rasch model with χ2 = 61.49, p = 0.00; PSI = 0.71. For perception of the teaching and assessment of EBP in the curriculum, 62% (8/13) items fit the Rasch model with χ2 = 80.99, p = 0.45; PSI = 0.92. perception of the teaching and assessment of EBP in the curriculum showed DIF in three items. The ICCs ranged between 0.80 and 0.98., Conclusions: The EBP-S measures were validated for physiotherapy students, including the testing of psychometric properties, which were not tested in the original studies. Further refinements should be considered for the use of the EBP-S with other groups of students or if changes are applied to the current curriculum., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Al Zoubi 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.)

A functional role has been ascribed to the human dihydrofolate reductase 2 (DHFR2) gene based on the enzymatic activity of recombinant versions of the predicted translated protein. However, the in vivo function is still unclear. The high amino acid sequence identity (92%) between DHFR2 and its parental homolog, DHFR, makes analysis of the endogenous protein challenging. This paper describes a targeted mass spectrometry proteomics approach in several human cell lines and tissue types to identify DHFR2-specific peptides as evidence of its translation. We show definitive evidence that the DHFR2 activity in the mitochondria is in fact mediated by DHFR, and not DHFR2. Analysis of Ribo-seq data and an experimental assessment of ribosome association using a sucrose cushion showed that the two main Ensembl annotated mRNA isoforms of DHFR2, 201 and 202, are differentially associated with the ribosome. This indicates a functional role at both the RNA and protein level. However, we were unable to detect DHFR2 protein at a detectable level in most cell types examined despite various RNA isoforms of DHFR2 being relatively abundant. We did detect a DHFR2-specific peptide in embryonic heart, indicating that the protein may have a specific role during embryogenesis. We propose that the main functionality of the DHFR2 gene in adult cells is likely to arise at the RNA level., Competing Interests: Conflict of interest The authors declare no competing interests., (Crown Copyright © 2024. Published by Elsevier Inc. All rights reserved.)

During the COVID-19 pandemic, contact tracing was used to identify individuals who had been in contact with a confirmed case so that these contacted individuals could be tested and quarantined to prevent further spread of the SARS-CoV-2 virus. Many countries developed mobile apps to find these contacted individuals faster. We evaluate the epidemiological effectiveness of the Dutch app CoronaMelder, where we measure effectiveness as the reduction of the reproduction number R. To this end, we use a simulation model of SARS-CoV-2 spread and contact tracing, informed by data collected during the study period (December 2020 - March 2021) in the Netherlands. We show that the tracing app caused a clear but small reduction of the reproduction number, and the magnitude of the effect was found to be robust in sensitivity analyses. The app could have been more effective if more people had used it, and if notification of contacts could have been done directly by the user and thus reducing the time intervals between symptom onset and reporting of contacts. The model has two innovative aspects: i) it accounts for the clustered nature of social networks and ii) cases can alert their contacts informally without involvement of health authorities or the tracing app., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Competing Interests: All authors have disclosed no conflicts of interest.

Background: Dolutegravir (DTG) is a recommended first-line regimen for all people with Human Immunodeficiency Virus (HIV) infection. Initial findings from Botswana, a country with no folate fortification program, showed an elevated prevalence of neural tube defects (NTDs) with peri-conceptional exposure to DTG. Here we explore whether a low folate diet influences the risk of DTG-associated foetal anomalies in a mouse model., Methods: C57BL/6 mice fed a folate-deficient diet for 2 weeks, were mated and then randomly allocated to control (water), or 1xDTG (2.5 mg/kg), or 5xDTG (12.5 mg/kg) both administered orally with 50 mg/kg tenofovir disoproxil fumarate 33.3 mg/kg emtricitabine. Treatment was administered once daily from gestational day (GD) 0.5 to sacrifice (GD15.5). Foetuses were assessed for gross anomalies. Maternal and foetal folate levels were quantified., Findings: 313 litters (103 control, 106 1xDTG, 104 5xDTG) were assessed. Viability, placental weight, and foetal weight did not differ between groups. NTDs were only observed in the DTG groups (litter rate: 0% control; 1.0% 1xDTG; 1.3% 5xDTG). Tail, abdominal wall, limb, craniofacial, and bleeding defects all occurred at higher rates in the DTG groups versus control. Compared with our previous findings on DTG usage in folate-replete mouse pregnancies, folate deficiency was associated with higher rates of several defects, including NTDs, but in the DTG groups only. We observed a severe left-right asymmetry phenotype that was more frequent in DTG groups than controls., Interpretation: Maternal folate deficiency may increase the risk for DTG-associated foetal defects. Periconceptional folic acid supplementation could be considered for women with HIV taking DTG during pregnancy, particularly in countries lacking folate fortification programs., Funding: This project has been funded by Federal funds from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, under Contract No. HHSN275201800001I and award #R01HD104553. LS is supported by a Tier 1 Canada Research Chair in Maternal-Child Health and HIV. HM is supported by a Junior Investigator award from the Ontario HIV Treatment Network., Competing Interests: Declaration of interests The authors have no conflicts of interest relating to this study., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objectives: The disease-modifying anti-rheumatic drug methotrexate (MTX) is recognized to reduce cardiovascular risk in patients with systemic inflammatory diseases. However, the molecular basis for these cardioprotective effects remains incompletely understood. This study evaluated the actions of low-dose MTX on the vascular endothelium., Methods: Human endothelial cells (EC) were studied under in vitro conditions relevant to inflammatory arthritis. These included culture in a pro-inflammatory microenvironment and exposure to fluid shear stress (FSS) using a parallel plate model. Respectively treated cells were analyzed by RNA sequencing and quantitative real-time PCR for gene expression, by immunoblotting for protein expression, by phosphokinase activity arrays, by flow cytometry for cell cycle analyses and by mass spectrometry to assess folate metabolite levels., Results: In static conditions, MTX was efficiently taken up by EC and caused cell cycle arrest concurrent with modulation of cell signaling pathways. These responses were reversed by folinic acid (FA), suggesting that OCM is a predominant target of MTX. Under FSS, MTX did not affect cell proliferation or pro-inflammatory gene expression. Exposure to FSS downregulated endothelial one carbon metabolism (OCM) as evidenced by decreased expression of key OCM genes and metabolites., Conclusion: We found that FSS significantly downregulated OCM and thereby rendered EC less susceptible to the effects of MTX treatment. The impact of shear stress on OCM suggested that MTX does not directly modulate endothelial function. The cardioprotective actions of MTX likely reflect direct actions on inflammatory cells and indirect benefit on the vascular endothelium., 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 © 2023 Lang, Leung, Greene, Malone, Saginc, Randi, Kiprianos, Maughan, Pericleous and Mason.)

Aim: We aimed to report the epidemiology of OHCA, bystander CPR pattern and other Utstein factors in a region in Hong Kong during the COVID-19 pandemic. In particular, we studied the relationship between COVID-19 incidence, OHCA incidence and survival outcome., Methods: This was a retrospective cohort study that used data from our registry to compare features of OHCA during pre-pandemic (Jan 2018 to Dec 2019), low-incidence pandemic (Jan 2020 to Dec 2021) and high-incidence pandemic (Jan to Mar 2022). We used multivariable logistic regression to identify survival predictors., Results: Incidence of OHCA increased dramatically with surging COVID-19 incidence (65.9 vs 74.2 vs 159.2 per 100,000 population per year, p  < 0.001). During the pandemic, there were more indoor OHCA (89.3% vs 92.6% vs 97.4%, p  < 0.001), fewer witnessed arrest (38.5% vs 38.3% vs 29.6%, p  = 0.001), and longer median time to basic life support upon receiving call (9 min vs 10 min vs 14 min, p  < 0.001). There was a higher proportion of OHCA cases with bystander-CPR (26.1% vs 31.3% vs 35.3%, p  < 0.001). The proportion of cases with survival to admission (STA) (30.8% vs 22.2% vs 15.4%, p  < 0.001) and survival to discharge (STD) (2.2% vs 1.0% vs 0.2%, p  = 0.001) were lowered. After controlling for confounders, the odds of STA was reduced by 33% and 55% during the low-incidence and high-incidence pandemic respectively., Conclusion: The increase in COVID-19 incidence had an exposure-response relationship with an increased incidence of OHCA and worsened survival outcomes., Competing Interests: 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., (© 2023 The Author(s).)

Skeletal dysplasias are a group of diseases characterized by bone and joint abnormalities, which can be detected during prenatal ultrasound. Next-generation sequencing has rapidly revolutionized molecular diagnostic approaches in fetuses with structural anomalies. This review studies the additional diagnostic yield of prenatal exome sequencing in fetuses with prenatal sonographic features of skeletal dysplasias. This was a systematic review by searching PubMed for studies published between 2013 and July 2022 that identified the diagnostic yield of exome sequencing after normal karyotype or chromosomal microarray analysis (CMA) for cases with suspected fetal skeletal dysplasias based on prenatal ultrasound. We identified 10 out of 85 studies representing 226 fetuses. The pooled additional diagnostic yield was 69.0%. The majority of the molecular diagnoses involved de novo variants (72%), while 8.7% of cases were due to inherited variants. The incremental diagnostic yield of exome sequencing over CMA was 67.4% for isolated short long bones and 77.2% for non-isolated cases. Among phenotypic subgroup analyses, features with the highest additional diagnostic yield were an abnormal skull (83.3%) and a small chest (82.5%). Prenatal exome sequencing should be considered for cases with suspected fetal skeletal dysplasias with or without a negative karyotype or CMA results. Certain sonographic features, including an abnormal skull and small chest, may indicate a potentially higher diagnostic yield.

Background: This prospective study assesses symptoms 3 months after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection compared to test-negative and population controls, and the effect of vaccination prior to infection., Methods: Participants enrolled after a positive (cases) or negative (test-negative controls) SARS-CoV-2 test, or after invitation from the general population (population controls). After 3 months, participants indicated presence of 41 symptoms and severity of 4 symptoms. Permutation tests were used to select symptoms significantly elevated in cases compared to controls and to compare symptoms between cases that were vaccinated or unvaccinated prior to infection., Results: In total, 9166 cases, 1698 symptomatic but test-negative controls, and 3708 population controls enrolled. At 3 months, 13 symptoms, and severity of fatigue, cognitive impairment, and dyspnea were significantly elevated incases compared to controls. Of cases, 48.5% reported ≥1 significantly elevated symptom compared to 29.8% of test-negative controls and 26.0% of population controls. Effect of vaccination could be determined for cases aged <65 years, and was significantly protective for loss of smell and taste but not for other symptoms., Discussion: Three months after SARS-CoV-2 infection, almost half of cases report symptoms, which was higher than background prevalence and test-negative prevalence. Vaccination prior to infection was protective against loss of smell and taste in cases aged <65 years., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To determine the prevalence of mitochondrial diseases (MD) in Hong Kong (HK) and to evaluate the clinical characteristics and genetic landscape of MD patients in the region., Methods: This study retrospectively reviewed the phenotypic and molecular characteristics of MD patients from participating public hospitals in HK between January 1985 to October 2020. Molecularly and/or enzymatically confirmed MD cases of any age were recruited via the Clinical Analysis and Reporting System (CDARS) using relevant keywords and/or International Classification of Disease (ICD) codes under the HK Hospital Authority or through the personal recollection of treating clinicians among the investigators., Results: A total of 119 MD patients were recruited and analyzed in the study. The point prevalence of MD in HK was 1.02 in 100,000 people (95% confidence interval 0.81-1.28 in 100,000). 110 patients had molecularly proven MD and the other nine were diagnosed by OXPHOS enzymology analysis or mitochondrial DNA depletion analysis with unknown molecular basis. Pathogenic variants in the mitochondrial genome (72 patients) were more prevalent than those in the nuclear genome (38 patients) in our cohort. The most commonly involved organ system at disease onset was the neurological system, in which developmental delay, seizures or epilepsy, and stroke-like episodes were the most frequently reported presentations. The mortality rate in our cohort was 37%., Conclusion: This study is a territory-wide overview of the clinical and genetic characteristics of MD patients in a Chinese population, providing the first available prevalence rate of MD in Hong Kong. The findings of this study aim to facilitate future in-depth evaluation of MD and lay the foundation to establish a local MD registry., (© 2023. The Author(s).)

Using color Doppler flow imaging or high-definition flow imaging with three-dimensional volume or spatio-temporal image correlation (STIC) in the glass-body mode allows displaying both gray-scale and color information of the heart cycle-related flow events and vessel spatial relationship. Conventionally, STIC in the glass-body mode has been used to examine the fetal heart and assess heart defects. Recently, a novel application of STIC in the visualization of abdominal precordial veins and intraplacental vascularization in singleton pregnancies has been reported. The aim of this present review is to discuss the use of color Doppler with three- and four-dimensional ultrasonography in the evaluation of extracardiac, placental, umbilical cord and twin abnormalities with examples. The glass-body mode is complementary to conventional 2D ultrasonography. Further studies are required to investigate use of the glass-body mode in the assessment of intraplacental vascularization in singleton and twin pregnancies.

Background: Early antiviral therapy was effective in the treatment of coronavirus disease 2019 (COVID-19). We assessed the efficacy and safety of combined interferon beta-1b and remdesivir treatment in hospitalized COVID-19 patients., Methods: We conducted a multicentre, prospective open-label, randomized-controlled trial involving high-risk adults hospitalized for COVID-19. Patients were randomly assigned to a 5-day interferon beta-1b 16 million units daily and remdesivir 200 mg loading on day 1 followed by 100 mg daily on day 2 to 5 (combination group), or to remdesivir only of similar regimen (control group) (1:1). The primary endpoint was the time to complete alleviation of symptoms (NEWS2 = 0)., Results: Two-hundred and twelve patients were enrolled. The median days of starting treatment from symptom onset was 3 days. The median age was 65 years, and 159 patients (75%) had chronic disease. The baseline demographics were similar. There was no mortality. For the primary endpoint, the combination group was significantly quicker to NEWS2 = 0 (4 vs 6.5 days; hazard ratio [HR], 6.59; 95% confidence interval [CI], 6.1-7.09; P < .0001) when compared to the control group. For the secondary endpoints, the combination group was quicker to negative nasopharyngeal swab (NPS) viral load (VL) (6 vs 8 days; HR, 8.16; 95% CI, 7.79-8.52; P < .0001) and to develop seropositive immunoglobulin G (IgG) (8 vs 10 days; HR, 10.78; 95% CI, 9.98-11.58; P < .0001). All adverse events resolved upon follow-up. Combination group (HR, 4.1 95% CI, 1.9-8.6, P < .0001) was the most significant independent factor associated with NEWS2 = 0 on day 4., Conclusions: Early treatment with interferon beta-1b and remdesivir was safe and better than remdesivir only in alleviating symptoms, and in shortening viral shedding and hospitalization with earlier seropositivity in high-risk COVID-19 patients., Clinical Trials Registration: NCT04647695., Competing Interests: Potential conflicts of interest. I. F. H received honoraria as speaker from MSD for COVID-19 Regional Expert Input Forum 2021 and Herpes Zoster lecture 2021 and was a member of the Advisory Board for Pfizer on COVID-19 Management 2022 and Gilead on Evolving Treatment Landscape in COVID-19 2021. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Conventionally, two- and three- dimensional color Doppler ultrasonography are used to examine the placental vascularization, but there are limitations in the examinations. In this report, spatiotemporal image correlation (STIC) volume acquisition in high-definition flow, displayed in glass-body mode was used to study the placental vascularization in eight pregnancies. At 20 weeks' gestation, STIC technique allowed visualization of blood flow in the intraplacental branches of the umbilical artery (IPB) and the spiral artery jets in a cardiac cycle. In particular, blood flow from a mega jet penetrating more than half of the placental thickness was demonstrated. Small blood flow from a tertiary order branch of the IPB traversing the placenta and sharply diminishing into the uterine wall was also demonstrated. There were differences in the IPB pattern between normal pregnancies and pregnancies at risk of fetal growth restriction/pre-eclampsia. There were also differences in the appearance of IPB between 20- and 33-weeks' gestation. The results of this report support that it is feasible to use STIC technology to study the placental vascularization. This novel application of STIC technology can increase the understanding of the complex vascularization., (© 2022 Wiley Periodicals LLC.)

Objective: To compare the incidences of early and late-onset neonatal sepsis, including group B streptococcus (GBS) and Escherichia coli (E. coli) before and after implementation of universal screening and intrapartum antibiotics prophylaxis (IAP)., Design: Retrospective cohort study., Setting: Eight public hospitals and 31 Maternal and Child Health Centres (in Hong Kong., Population: 460 552 women attending routine antenatal service from 2009 to 2020., Methods: Universal culture-based GBS screening has been offered to eligible women since 2012. Total births, GBS screening tests, maternal GBS colonisation and neonatal sepsis with positive blood or cerebrospinal fluid were retrieved from clinical and laboratory database., Main Outcome Measures: Maternal GBS colonisation rate, early- and late-onset neonatal sepsis (including GBS and E. coli)., Results: Of 318 740 women with universal culture-based screening, 63 767 women (20.0%) screened positive. After implementation of GBS screening and IAP, the incidence of early-onset neonatal sepsis decreased (3.25 versus 2.26 per 1000 live births, p < 0.05), including those caused by GBS (1.03 versus 0.26 per 1000 live births, p < 0.05). Segmented regression showed that change in early-onse GBS sepsis incidence after screening was the only significant variable in the outcome trend. There was no significant evidence of increase in incidence of late-onset neonatal sepsis including those caused by GBS., Conclusions: Universal culture-based GBS screening and IAP were associated with reduction in early-onset neonatal sepsis including GBS disease. Although an increase in incidence of late-onset neonatal sepsis including those caused by GBS cannot be totally ruled out, we did not identify significant evidence that this occurred., (© 2022 John Wiley & Sons Ltd.)

Edwardsiella species in aquatic environments exist either as individual planktonic cells or in communal biofilms. These organisms encounter multiple stresses, include changes in salinity, pH, temperature, and nutrients. Pathogenic species such as E. piscicida , can multiply within the fish hosts. Additionally, Edwardsiella species ( E. tarda ), can carry antibiotic resistance genes (ARGs) on chromosomes and/or plasmids, that can be transmitted to the microbiome via horizontal gene transfer. E. tarda serves as a core in the aquatic resistome. Edwardsiela uses molecular switches (RpoS and EsrB) to control gene expression for survival in different environments. We speculate that free-living Edwardsiella can transition to host-living and vice versa, using similar molecular switches. Understanding such transitions can help us understand how other similar aquatic bacteria switch from free-living to become pathogens. This knowledge can be used to devise ways to slow down the spread of ARGs and prevent disease outbreaks in aquaculture and clinical settings.

BackgroundSince the roll-out of COVID-19 vaccines in late 2020 and throughout 2021, European governments have relied on mathematical modelling to inform policy decisions about COVID-19 vaccination.AimWe present a scenario-based modelling analysis in the Netherlands during summer 2021, to inform whether to extend vaccination to adolescents (12-17-year-olds) and children (5-11-year-olds).MethodsWe developed a deterministic, age-structured susceptible-exposed-infectious-recovered (SEIR) model and compared modelled incidences of infections, hospital and intensive care admissions, and deaths per 100,000 people across vaccination scenarios, before the emergence of the Omicron variant.ResultsOur model projections showed that, on average, upon the release of all non-pharmaceutical control measures on 1 November 2021, a large COVID-19 wave may occur in winter 2021/22, followed by a smaller, second wave in spring 2022, regardless of the vaccination scenario. The model projected reductions in infections/severe disease outcomes when vaccination was extended to adolescents and further reductions when vaccination was extended to all people over 5 years-old. When examining projected disease outcomes by age group, individuals benefitting most from extending vaccination were adolescents and children themselves. We also observed reductions in disease outcomes in older age groups, particularly of parent age (30-49 years), when children and adolescents were vaccinated, suggesting some prevention of onward transmission from younger to older age groups.ConclusionsWhile our scenarios could not anticipate the emergence/consequences of SARS-CoV-2 Omicron variant, we illustrate how our approach can assist decision making. This could be useful when considering to provide booster doses or intervening against future infection waves.

Background: Myo-inositol (MI) is incorporated into numerous biomolecules, including phosphoinositides and inositol phosphates. Disturbance of inositol availability or metabolism is associated with various disorders, including neurological conditions and cancers, whereas supplemental MI has therapeutic potential in conditions such as depression, polycystic ovary syndrome, and congenital anomalies. Inositol status can be influenced by diet, synthesis, transport, utilization, and catabolism., Objectives: We aimed to investigate potential genetic regulation of circulating MI status and to evaluate correlation of MI concentration with other metabolites., Methods: GC-MS was used to determine plasma MI concentration of >2000 healthy, young adults (aged 18-28 y) from the Trinity Student Study. Genotyping data were used to test association of plasma MI with single nucleotide polymorphisms (SNPs) in candidate genes, encoding inositol transporters and synthesizing enzymes, and test for genome-wide association. We evaluated potential correlation of plasma MI with d-chiro-inositol (DCI), glucose, and other metabolites by Spearman rank correlation., Results: Mean plasma MI showed a small but significant difference between males and females (28.5 and 26.9 μM, respectively). Candidate gene analysis revealed several nominally significant associations with plasma MI, most notably for SLC5A11 (solute carrier family 5 member 11), encoding a sodium-coupled inositol transporter, also known as SMIT2 (sodium-dependent myo-inositol transporter 2). However, these did not survive correction for multiple testing. Subsequent testing for genome-wide association with plasma MI did not identify associations of genome-wide significance (P < 5 × 10 -8 ). However, 8 SNPs exceeded the threshold for suggestive significant association with plasma MI concentration (P < 1 × 10 -5 ), 3 of which were located within or close to genes: MTDH (metadherin), LAPTM4B (lysosomal protein transmembrane 4 β), and ZP2 (zona pellucida 2). We found significant positive correlation of plasma MI concentration with concentration of dci and several other biochemicals including glucose, methionine, betaine, sarcosine, and tryptophan., Conclusions: Our findings suggest potential for modulation of plasma MI in young adults by variation in SLC5A11, which is worthy of further investigation., (Copyright © 2022 American Society for Nutrition.)