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SUMMARY: This study uses crisis management and organizational culture theories to understand how audit engagement leaders' responses to challenges during the COVID-19 pandemic provide insight into audit firm culture. Semi-structured interviews with 22 U.S. audit engagement leaders during and after the pandemic reveal consistencies and inconsistencies among the organizational mechanisms used to convey and embed underlying cultural values. We find that audit engagement leaders consistently espouse and reinforce professionalism and commercialism as strong values of audit firm culture. However, in maintaining both of these values during the pandemic, leaders respond inconsistently to learning and development, as well as auditors' mental health and well-being, despite their potential long-term impacts on professionalism and commercialism, suggesting that these are weaker cultural values. The findings reveal the short-term myopia of the audit profession on audit quality and firm profitability. Our findings have important implications for research and practice. JEL Classifications: M40; M42. [ABSTRACT FROM AUTHOR]

This study explored the practices of Grade 3 teachers in Cataingan East District, employing an Explanatory-Sequential Study design to identify strategies, assess efficacy, address challenges, and determine support needs. Quantitative analysis scrutinized socio-demographic profiles, teaching strategies, and effectiveness perceptions, while qualitative inquiry through thematic analysis delved into challenges and support mechanisms. Participants included 21 elementary teachers from Cataingan East District, predominantly female, married, and experienced, representing diverse backgrounds. Commonly used strategies such as Vocabulary Instruction and Interactive Read-Aloud were identified, with potential enhancements suggested for areas like Literature Circles. Phonics Instruction emerged as highly effective. Challenges included student reading levels, learning styles, resource scarcity, waning student interest, and parental involvement. Teachers articulated requisites for enhanced literacy instruction, including conducive environments, tutoring support, parental involvement, ongoing training, ample resources, and mentorship opportunities. Recommendations emphasized supporting teacher professional development, fostering collaborative instructional approaches, ensuring sustained support and resource availability, developing targeted interventions, and nurturing a supportive teaching environment. These insights advocated tailored initiatives aimed at empowering Grade 3 teachers, optimizing teaching practices, and addressing systemic challenges in literacy instruction, ultimately fostering student success and promoting holistic educational development. [ABSTRACT FROM AUTHOR]

Homelessness increases the risk of acquiring an infectious disease. We conducted a systematic review of the literature to identify quantitative data related to infectious diseases and homelessness. We searched Google Scholar, PubMed, and SCOPUS for quantitative literature published from January 2003 through December 2022 in English from the United States and Canada. We excluded literature on vaccine-preventable diseases and HIV because these diseases were recently reviewed. Of the 250 articles that met inclusion criteria, more than half were on hepatitis C virus or Mycobacterium tuberculosis. Other articles were on COVID-19, respiratory syncytial virus, Staphylococcus aureus, group A Streptococcus, mpox (formerly monkeypox), 5 sexually transmitted infections, and gastrointestinal or vectorborne pathogens. Most studies showed higher prevalence, incidence, or measures of risk for infectious diseases among people experiencing homelessness as compared with people who are housed or the general population. Although having increased published data that quantify the infectious disease risks of homelessness is encouraging, many pathogens that are known to affect people globally who are not housed have not been evaluated in the United States or Canada. Future studies should focus on additional pathogens and factors leading to a disproportionately high incidence and prevalence of infectious diseases among people experiencing homelessness. [ABSTRACT FROM AUTHOR]

This article presents a methodology for program managers to effectively monitor and control scope, schedule, and cost in programs that use the Rolling Wave lifecycle. It explains the differences between predictive and adaptive lifecycles and discusses the challenges of scaling up the Rolling Wave methodology for program management. The article also addresses the interdependencies between multiple projects within a program and suggests a structural solution to manage them. It introduces a program-level dashboard that includes various tools for project management, such as a Gantt chart view, an Early Warning System, a change order report, and a display of upcoming tasks and late starts. The article emphasizes the importance of communication and updates among project managers to minimize disruptions and manage risk and quality. [Extracted from the article]

Matrix isolation infrared spectroscopy was used to characterize a 1:1 complex of methanol (CH3OH) and benzene (C6H6). Co-deposition experiments with CH3OH and C6H6 were performed at 17–20 K using nitrogen and argon as the matrix gases. Several new infrared peaks in the co-deposition spectra were observed near the fundamental absorptions of the CH3OH and C6H6 parent molecules and these new peaks have been attributed to CH3OH–C6H6 complexe. Experiments were also performed with isotopic CD3OD and C6D6 and the corresponding infrared peaks of the isotopologue complexes have also been observed. Theoretical calculations were performed for the CH3OH–C6H6 complex using the M06-2X, ωB97X-D, MP2, and CCSD(T) methods with the aug-cc-pVDZ and aug-cc-pVTZ basis sets. Full geometry optimizations followed by vibrational frequency calculations were performed for several initial starting geometries and three stable minima were found for the CH3OH–C6H6 complex. The first has the CH3OH above the C6H6 ring with the OH hydrogen interacting with the π cloud of the ring (H–π complex), the second has the CH3OH above the C6H6 ring with the OH oxygen interacting with one or two of the C–H bonds of the ring (CH–O 1 complex), and the third has the CH3OH towards the side of the C6H6 ring with the OH oxygen interacting with two of the C–H bonds of the ring (CH–O 2 complex). The H–π complex structure is predicted to be the lower energy structure by ∼8 kJ/mol compared to the two CH–O structures. Comparing the theoretically predicted infrared spectra for the optimized CH3OH–C6H6 complex structures to the experimentally observed infrared peaks in argon and nitrogen matrices, it is concluded that in the argon matrices only the H–π complex structure is being observed, whereas in the nitrogen matrices the H–π complex and CH–O 1 complex structures are being observed. [ABSTRACT FROM AUTHOR]

This tutorial demonstrates the use of information geometry tools in analyzing environmental parameter sensitivities in underwater acoustics. Sensitivity analyses quantify how well data can constrain model parameters, with application to inverse problems like geoacoustic inversion. A review of examples of parameter sensitivity methods and their application to problems in underwater acoustics is given, roughly grouped into "local" and "non-local" methods. Local methods such as Fisher information and Cramér-Rao bounds have important connections to information geometry. Information Geometry combines the fields of information theory and differential geometry by interpreting a model as a Riemannian manifold, known as the model manifold, that encodes both local and global parameter sensitivities. As an example, 2-dimensional model manifold slices are constructed for the Pekeris waveguide with sediment attenuation, for a vertical array of hydrophones. This example demonstrates how effective, reduced-order models emerge in certain parameter limits, which correspond to boundaries of the model manifold. This example also demonstrates how the global structure of the model manifold influences the local sensitivities quantified by the Fisher information matrix. This paper motivates future work to utilize information geometry methods for experimental design and model reduction applied to more complex modeling scenarios in underwater acoustics. [ABSTRACT FROM AUTHOR]

Introduction: Second language learning is a multifaceted task that benefits across numerous neurocognitive domains including central auditory processing. Existing cross-sectional and longitudinal data show that performance on tests of central auditory processing [central auditory tests (CATs)] worsens with HIV infection. Second language learning may modify this relationship. To explore the relationship between second language learning, central auditory processing, and its interaction with HIV, we assessed the effect of learning English as a second language on CATs among children both living with and without HIV (CLWH/CLWOH) in Dar es Salaam, Tanzania. Methods: Three hundred and seventy-two native Kiswahili speaking children aged 3-10 years old (196 CLWOH, 176 CLWH) were enrolled. Participants completed questionnaires about English language learning, socioeconomic status (SES), and health history. Three central auditory tests-the Triple Digit Test (TDT), the Staggered Spondaic Word Test (SSW), and the Hearing-In-Noise Test (HINT)-were used to assess each participant's central auditory processing abilities. Multivariate linear regression was used to assess the effect of written and spoken English language learning at home and in school on CATs with age, HIV-status, and SES included in each model. Results: HIV status, age, and SES were all significant predictors of all three central auditory tests, with CLWH performing significantly worse on all three CATs than CLWOH. Children actively learning spoken and written English at home had significantly better central auditory processing abilities on the TDT compared to children not actively learning English at home (p < 0.01) independent of HIV status, age, and SES. Children learning spoken and written English at school performed significantly better on the HINT (p < 0.05) than those not actively learning English at school. Discussion: Learning English at home and learning English in school were associated with improved central auditory performance independent of HIV status, SES, and age. These findings also underscore the significance of second language acquisition as a potential mechanism of improving central auditory function within a Kiswahili-speaking cohort. This study found differences in central auditory processing between children exposed to English at home and in school, suggesting differences in language learning in both settings mediated by SES, and this benefit exists regardless of HIV status. [ABSTRACT FROM AUTHOR]

The model manifold, an information geometry tool, is a geometric representation of a model that can quantify the expected information content of modeling parameters. For a normal-mode sound propagation model in a shallow ocean environment, transmission loss (TL) is calculated for a vertical line array and model manifolds are constructed for both absolute and relative TL. For the example presented in this paper, relative TL yields more compact model manifolds with seabed environments that are less statistically distinguishable than manifolds of absolute TL. This example illustrates how model manifolds can be used to improve experimental design for inverse problems. [ABSTRACT FROM AUTHOR]

Respiratory infections are one of the most common causes of illness and morbidity in neonates worldwide. In the acute phase infections are known to cause wide-spread peripheral inflammation. However, the inflammatory consequences to the critical neural control centres for respiration have not been explored. Utilising a well characterised model of neonatal respiratory infection, we investigated acute responses within the medulla oblongata which contains key respiratory regions. Neonatal mice were intranasally inoculated within 24 h of birth, with either Chlamydia muridarum or sham-infected, and tissue collected on postnatal day 15, the peak of peripheral inflammation. A key finding of this study is that, while the periphery appeared to show no sex-specific effects of a neonatal respiratory infection, sex had a significant impact on the inflammatory response of the medulla oblongata. There was a distinct sex-specific response in the medulla coincident with peak of peripheral inflammation, with females demonstrating an upregulation of anti-inflammatory cytokines and males showing very few changes. Microglia also demonstrated sex-specificity with the morphology of females and males differing based upon the nuclei. Astrocytes showed limited changes during the acute response to neonatal infection. These data highlight the strong sex-specific impact of a respiratory infection can have on the medulla in the acute inflammatory phase. [ABSTRACT FROM AUTHOR]

The model manifold, an information geometry tool, is a geometric representation of a model that can quantify the expected information content of modeling parameters. For a normal-mode sound propagation model in a shallow ocean environment, transmission loss (TL) is calculated for a vertical line array and model manifolds are constructed for both absolute and relative TL. For the example presented in this paper, relative TL yields more compact model manifolds with seabed environments that are less statistically distinguishable than manifolds of absolute TL. This example illustrates how model manifolds can be used to improve experimental design for inverse problems. [ABSTRACT FROM AUTHOR]

In a series of experiments involving beliefs and misinformation beliefs, we find that individuals who are prompted with a counterfactual mindset are significantly more likely to change their existing beliefs when presented with evidence that contradicts their beliefs. While research finds that beliefs that are considered part of one's identity are highly resistant to change in the face of evidence that challenges these beliefs, four experiments provide evidence that counterfactual generation causes individuals to adjust beliefs and correct misinformation beliefs in response to contradicting evidence. Indeed, we find that a counterfactual mindset was effective in promoting incorporation of accurate facts and causing individuals to revise misinformation beliefs about COVID vaccination safety for a large sample of individuals who have rejected COVID vaccinations. Finally, the results of the psychophysiological experiment reveal that counterfactual generation alters decision makers' search strategies, increases their cognitive arousal in response to evidence that challenges their beliefs, and increases their desire to seek out disconfirming evidence. Overall, the four experiments indicate that counterfactual generation can effectively activate mindsets that increase individuals' willingness to evaluate evidence that contradicts their beliefs and adjust their beliefs in response to evidence. [ABSTRACT FROM AUTHOR]

We report the fabrication and measurement of quantum flux parametron logic from high-transition-temperature Josephson junctions operating at 25 K, above the temperature of liquid helium. The circuits are written directly into the plane of a single-layer thin film of YBa2Cu3O7 using a focused helium ion beam. A single-cell quantum flux parametron was constructed and correct logic operation was verified by using an on-chip superconducting quantum interference device for readout. A three-cell shift register was also fabricated and tested using a three-phase clock cycle. We estimate the average bit energy to be about 1 × 10 − 20 J at 1 GHz. [ABSTRACT FROM AUTHOR]

Circadian clocks temporally coordinate daily organismal biology over the 24-h cycle. Their molecular design, preserved between fungi and animals, is based on a core-oscillator composed of a one-step transcriptional-translational-negative-feedback-loop (TTFL). To test whether this evolutionarily conserved TTFL architecture is the only plausible way for achieving a functional circadian clock, we adopted a transcriptional rewiring approach, artificially co-opting regulators of the circadian output pathways into the core-oscillator. Herein we describe one of these semi-synthetic clocks which maintains all basic circadian features but, notably, it also exhibits new attributes such as a "lights-on timer" logic, where clock phase is fixed at the end of the night. Our findings indicate that fundamental circadian properties such as period, phase and temperature compensation are differentially regulated by transcriptional and posttranslational aspects of the clockworks. Synopsis: Eukaryotic circadian oscillators share a one-step transcription-translation negative-feedback loop (TTFL) circuit design, where a main transcriptional complex drives expression of a negative element that can inhibit its own expression. Here, a transcriptional rewiring strategy in the fungus N. crassa reveals that this basic circuit topology can be dramatically changed, while still yielding a functional semi-synthetic clock. Placing the transcription of the negative component frq under the control of the output promoter con-10 alters its regulation, while still yielding rhythmic expression. In the resulting functional semi-synthetic circuit, frq expression is now under the control of circadian clock downstream components. FRQ phosphorylation has a more pronounced effect on circadian period length and temperature compensation than its transcriptional regulation. In the semi-synthetic oscillator, the circadian rhythm phase is now determined by the moment the light is turned on. Co-option of downstream transcription factors into the main transcriptional circuit of the circadian clock in the fungus Neurospora crassa leads to altered clock phase determination. [ABSTRACT FROM AUTHOR]

Importance: Predicting neurocognitive deficits using complex auditory assessments could change how cognitive dysfunction is identified, and monitored over time. Detecting cognitive impairment in people living with HIV (PLWH) is important for early intervention, especially in low- to middle-income countries where most cases exist. Auditory tests relate to neurocognitive test results, but the incremental predictive capability beyond demographic factors is unknown. Objective: Use machine learning to predict neurocognitive deficits, using auditory tests and demographic factors. Setting: The Infectious Disease Center in Dar es Salaam, Tanzania Participants: Participants were 939 Tanzanian individuals from Dar es Salaam living with and without HIV who were part of a longitudinal study. Patients who had only one visit, a positive history of ear drainage, concussion, significant noise or chemical exposure, neurological disease, mental illness, or exposure to ototoxic antibiotics (e.g., gentamycin), or chemotherapy were excluded. This provided 478 participants (349 PLWH, 129 HIV-negative). Participant data were randomized to training and test sets for machine learning. Main outcome(s) and measure(s): The main outcome was whether auditory variables combined with relevant demographic variables could predict neurocognitive dysfunction (defined as a score of <26 on the Kiswahili Montreal Cognitive Assessment) better than demographic factors alone. The performance of predictive machine learning algorithms was primarily evaluated using the area under the receiver operational characteristic curve. Secondary metrics for evaluation included F1 scores, accuracies, and the Youden's indices for the algorithms. Results: The percentage of individuals with cognitive deficits was 36.2% (139 PLWH and 34 HIV-negative). The Gaussian and kernel naïve Bayes classifiers were the most predictive algorithms for neurocognitive impairment. Algorithms trained with auditory variables had average area under the curve values of 0.91 and 0.87, F1 scores (metric for precision and recall) of 0.81 and 0.76, and average accuracies of 86.3% and 81.9% respectively. Algorithms trained without auditory variables as features were statistically worse (p <.001) in both the primary measure of area under the curve (0.82/0.78) and the secondary measure of accuracy (72.3%/74.5%) for the Gaussian and kernel algorithms respectively. Conclusions and relevance: Auditory variables improved the prediction of cognitive function. Since auditory tests are easy-to-administer and often naturalistic tasks, they may offer objective measures or predictors of neurocognitive performance suitable for many global settings. Further research and development into using machine learning algorithms for predicting cognitive outcomes should be pursued. [ABSTRACT FROM AUTHOR]

We report the fabrication and testing of arrays of nanoscale superconducting quantum interference devices (SQUIDs) directly written into a thin film of the high-transition temperature superconductor YBa2Cu-3O7−δ with a focused helium ion beam. We compare three array configurations with 400 nm by 400 nm nanoSQUIDs connected in series and parallel and a two-dimensional (2D) combination of both. Our electrical transport measurements show that series arrays of three nanoSQUIDs exhibit modulation voltages greater than 1 mV and that combining the devices in parallel greatly enhances the slope of the voltage–magnetic field characteristic. A 2D array with 3 SQUIDS in series and 7 in parallel exhibited a transfer function of 5.51 mV/mT. [ABSTRACT FROM AUTHOR]

Thymic stromal lymphopoietin (TSLP) is an epithelial-derived pleiotropic cytokine that regulates T-helper 2 (Th2) immune responses in the lung and plays a major role in severe uncontrolled asthma. Emerging evidence suggests a role for endoplasmic reticulum (ER) stress in the pathogenesis of asthma. In this study, we determined if ER stress and the unfolded protein response (UPR) signaling are involved in TSLP induction in the airway epithelium. For this, we treated human bronchial epithelial basal cells and differentiated primary bronchial epithelial cells with ER stress inducers and the TSLP mRNA and protein expression was determined. A series of siRNA gene knockdown experiments were conducted to determine the ER stress-induced TSLP signaling pathways. cDNA collected from asthmatic bronchial biopsies was used to determine the gene correlation between ER stress and TSLP. Our results show that ER stress signaling induces TSLP mRNA expression via the PERK-C/EBP homologous protein (CHOP) signaling pathway. AP-1 transcription factor is important in regulating this ER stress-induced TSLP mRNA induction, though ER stress alone cannot induce TSLP protein production. However, ER stress significantly enhances TLR3-induced TSLP protein secretion in the airway epithelium. TSLP and ER stress (PERK) mRNA expression positively correlates in bronchial biopsies from participants with asthma, particularly in neutrophilic asthma. In conclusion, these results suggest that ER stress primes TSLP that is then enhanced further upon TLR3 activation, which may induce severe asthma exacerbations. Targeting ER stress using pharmacological interventions may provide novel therapeutics for severe uncontrolled asthma. NEW & NOTEWORTHY: TSLP is an epithelial-derived cytokine and a key regulator in the pathogenesis of severe uncontrolled asthma. We demonstrate a novel mechanism by which endoplasmic reticulum stress signaling upregulates airway epithelial TSLP mRNA expression via the PERK-CHOP signaling pathway and enhances TLR3-mediated TSLP protein secretion. [ABSTRACT FROM AUTHOR]

Diabetic kidney disease (DKD) is a major microvascular complication of both type 1 and type 2 diabetes. DKD is characterised by injury to both glomerular and tubular compartments, leading to kidney dysfunction over time. It is one of the most common causes of chronic kidney disease (CKD) and end-stage renal disease (ESRD). Persistent high blood glucose levels can damage the small blood vessels in the kidneys, impairing their ability to filter waste and fluids from the blood effectively. Other factors like high blood pressure (hypertension), genetics, and lifestyle habits can also contribute to the development and progression of DKD. The key features of renal complications of diabetes include morphological and functional alterations to renal glomeruli and tubules leading to mesangial expansion, glomerulosclerosis, homogenous thickening of the glomerular basement membrane (GBM), albuminuria, tubulointerstitial fibrosis and progressive decline in renal function. In advanced stages, DKD may require treatments such as dialysis or kidney transplant to sustain life. Therefore, early detection and proactive management of diabetes and its complications are crucial in preventing DKD and preserving kidney function. [ABSTRACT FROM AUTHOR]

The article discusses the potential therapeutic impact of the GPR84 antagonist GLPG1205 in experimental severe asthma. It emphasizes GPR84's role in lung inflammation and metabolism, as well as the compound's effect on reducing airway inflammation and hyperresponsiveness, particularly in neutrophilic inflammation and steroid-insensitive features.

In this day and age, the world has slowly been shifting to the widespread use of technology in almost all aspects, including employment. This is proven by the continuous growth in the number of remote jobs globally, which allows people to work from home through the use of technology anytime and anywhere. Naturally, challenges and dilemmas, especially when it comes to communication, arise in the workplace. However, the challenges experienced in the face-to-face setup may differ from what is experienced in a remote or online setup. That being said, this research aims to discover the organizational culture being practiced in a remote work setup, specifically its organizational culture, communication flow, and practices, as well as the communication model being observed in the workplace through the conduction of an interview between two engineers. The findings reveal that the organization has both linguistic diversity and cultural pluralism. Moreover, their primary communication channels are digital tools, which is an indication that the Interactive model of communication is observed in their company. In addition, employees, irrespective of their positions, are also given the chance to participate and talk during meetings, which signifies that the company's communication flows are both vertical and horizontal. Lastly, technological barriers like internet connectivity impact project development, which may lead to miscommunications in the workplace. Overall, the research sheds light on communication challenges and practices in remote work environments while also highlighting the healthy work atmosphere the selected organization has cultivated. [ABSTRACT FROM AUTHOR]

Single case studies of extraordinary disease resilience may provide therapeutic insight into conditions for which no definitive treatments exist. An otherwise healthy 35-year-old man (patient-R) with the canonical pathogenic ACVR1R206H variant and the classic congenital great toe malformation of fibrodysplasia ossificans progressiva (FOP) had extreme paucity of post-natal heterotopic ossification (HO) and nearly normal mobility. We hypothesized that patient-R lacked a sufficient post-natal inflammatory trigger for HO. A plasma biomarker survey revealed a reduction in total matrix metalloproteinase-9 (MMP-9) compared to healthy controls and individuals with quiescent FOP. Whole exome sequencing identified compound heterozygous variants in MMP-9 (c.59C > T, p.A20V and c.493G > A, p.D165N). Structural analysis of the D165N variant predicted both decreased MMP-9 secretion and activity that were confirmed by enzyme-linked immunosorbent assay and gelatin zymography. Further, human proinflammatory M1-like macrophages expressing either MMP-9 variant produced significantly less Activin A, an obligate ligand for HO in FOP, compared to wildtype controls. Importantly, MMP-9 inhibition by genetic, biologic, or pharmacologic means in multiple FOP mouse models abrogated trauma-induced HO, sequestered Activin A in the extracellular matrix (ECM), and induced regeneration of injured skeletal muscle. Our data suggest that MMP-9 is a druggable node linking inflammation to HO, orchestrates an existential role in the pathogenesis of FOP, and illustrates that a single patient's clinical phenotype can reveal critical molecular mechanisms of disease that unveil novel treatment strategies. [ABSTRACT FROM AUTHOR]

Chronic hyperglycemia induces intrarenal oxidative stress due to the excessive production of reactive oxygen species (ROS), leading to a cascade of events that contribute to the development and progression of diabetic kidney disease (DKD). NOX5, a pro-oxidant NADPH oxidase isoform, has been identified as a significant contributor to renal ROS in humans. Elevated levels of renal ROS contribute to endothelial cell dysfunction and associated inflammation, causing increased endothelial permeability, which can disrupt the renal ecosystem, leading to progressive albuminuria and renal fibrosis in DKD. This study specifically examines the contribution of endothelial cell-specific human NOX5 expression in renal pathology in a transgenic mouse model of DKD. This study additionally compares NOX5 with the previously characterized NADPH oxidase, NOX4, in terms of their relative roles in DKD. Regardless of NOX4 pathway, this study found that endothelial cell-specific expression of NOX5 exacerbates renal injury, albuminuria and fibrosis. This is attributed to the activation of the endothelial mesenchymal transition (EMT) pathway via enhanced ROS formation and the modulation of redox-sensitive factors. These findings underscore the potential therapeutic significance of NOX5 inhibition in human DKD. The study proposes that inhibiting NOX5 could be a promising approach for mitigating the progression of DKD and strengthens the case for the development of NOX5-specific inhibitors as a potential therapeutic intervention. [ABSTRACT FROM AUTHOR]

Purpose: To explore the association between widefield swept-source optical coherence tomography angiography (WF SS-OCTA) metrics, including nonperfusion area (NPA) and neovascularization (NV), and presence of neovascular glaucoma (NVG) in patients with proliferative diabetic retinopathy (PDR). Methods: A prospective, cross-sectional study was conducted from November 2018 to February 2020. A total of 85 eyes of 60 PDR patients without NVG and 9 eyes of 8 PDR patients with NVG were included. Retinal ischemic parameters (NPA; ischemia index [NPA/total retinal area]) and NV features (NV number; NV area; NV vessel density) were evaluated. Foveal avascular zone (FAZ), macular thickness/volume, and choroidal thickness/volume were obtained using the Zeiss ARI Network. WF SS-OCTA retinal and choroidal metrics, systemic, and ocular parameters were screened using Least Absolute Shrinkage and Selection Operator (LASSO) logistic regression for variable selection. Firth's bias-reduced logistic regression (outcome: presence of NVG) was subsequently used to identify parameters associated with NVG. Results: After LASSO variable selection, 8 variables were significantly associated with the presence of NVG: DM duration (years), insulin (yes/no), best-corrected visual acuity (BCVA) (logMAR), IOP, ischemia index, skeletonized vessel density, macular thickness (inner inferior, outer temporal regions). Firth's bias-reduced logistic regression showed ischemia index (odds ratio [OR]=13.2, 95% confidence interval [CI]:5.3–30.7, P<0.001) and BCVA (OR=5.8, 95%CI:1.2–28.8, P<0.05) were associated with the presence of NVG. NV metrics, FAZ, and choroidal parameters were not related to NVG. Conclusions: Retinal ischemia but not NV was associated with the presence of NVG in patients with PDR using WF SS-OCTA. Larger, longitudinal studies are needed to validate imaging biomarkers associated with diabetic NVG. [ABSTRACT FROM AUTHOR]

Succinate is a potent immune signalling molecule that is present in the mammalian gut and within macrophages. Both of these infection niches are colonised by the pathogenic bacterium Salmonella enterica serovar Typhimurium during infection. Succinate is a C4-dicarboyxlate that can serve as a source of carbon for bacteria. When succinate is provided as the sole carbon source for in vitro cultivation, Salmonella and other enteric bacteria exhibit a slow growth rate and a long lag phase. This growth inhibition phenomenon was known to involve the sigma factor RpoS, but the genetic basis of the repression of bacterial succinate utilisation was poorly understood. Here, we use an experimental evolution approach to isolate fast-growing mutants during growth of S. Typhimurium on succinate containing minimal medium. Our approach reveals novel RpoS-independent systems that inhibit succinate utilisation. The CspC RNA binding protein restricts succinate utilisation, an inhibition that is antagonised by high levels of the small regulatory RNA (sRNA) OxyS. We discovered that the Fe-S cluster regulatory protein IscR inhibits succinate utilisation by repressing the C4-dicarboyxlate transporter DctA. Furthermore, the ribose operon repressor RbsR is required for the complete RpoS-driven repression of succinate utilisation, suggesting a novel mechanism of RpoS regulation. Our discoveries shed light on the redundant regulatory systems that tightly regulate the utilisation of succinate. We speculate that the control of central carbon metabolism by multiple regulatory systems in Salmonella governs the infection niche-specific utilisation of succinate. Author summary: During infection, Salmonella enterica serovar Typhimurium must efficiently utilise the nutrients provided by the host and the microbiota. Within host niches colonised by Salmonella, key carbon source is succinate, which is abundant in both the gut and within macrophages. Although S. Typhimurium possesses all the molecular machinery to import and catabolise succinate, the utilisation of this carbon source is strongly inhibited under laboratory conditions. Here, we have used diverse genetic approaches to discover that several distinct genetic regulatory systems act in concert to repress succinate utilisation by Salmonella. Our study sheds new light on how carbon source utilisation is managed by this important model enteropathogenic bacterium. [ABSTRACT FROM AUTHOR]

This exploratory study examined whether central auditory tests show differences between people living with HIV (PLWH) treated with two predominant antiretroviral drug therapy (ART) regimens. Cross-sectional. 253 PLWH (mean age 39.8 years) from the Shanghai Public Health Clinical Centre, China. The Hearing in Noise Test speech reception threshold (SRT) assessed central auditory function and the Montreal Cognitive Assessment (MoCA) assessed cognition. The relationship between ART regimen and SRT was evaluated with multivariable linear regression incorporating age, HIV duration, and peripheral hearing ability. Multivariable logistic regression was used to ascertain if SRT and ART regimen predicted MoCA impairment. The two predominant ART regimens differed by one drug (zidovudine or tenofovir). Participants taking the zidovudine-containing regimen had poorer SRT performance (p=.012) independent of age and hearing thresholds. MoCA scores did not differ between drug regimens, but a negative relationship was found between SRT and MoCA impairment (p=.048). ART regimens differed in their association with central auditory test performance likely reflecting neurocognitive changes in PLWH taking the zidovudine-containing regimen. Central auditory test performance also marginally predicted cognitive impairment, supporting further assessment of central auditory tests to detect neurocognitive deficits in PLWH. [ABSTRACT FROM AUTHOR]

Aims: Previously, retinoids have decreased CYP2D6 mRNA expression in vitro and induced CYP3A4 in vitro and in vivo. This study aimed to determine whether isotretinoin administration changes CYP2D6 and CYP3A activities in patients with severe acne. Methods: Thirty‐three patients (22 females and 11 males, 23.5 ± 6.0 years old) expected to receive isotretinoin treatment completed the study. All participants were genotyped for CYP2D6 and CYP3A5. Participants received dextromethorphan (DM) 30 mg orally as a dual‐probe substrate of CYP2D6 and CYP3A activity at two study timepoints: pre‐isotretinoin treatment and with isotretinoin for at least 1 week. The concentrations of isotretinoin, DM and their metabolites were measured in 2‐h postdose plasma samples and in cumulative 0‐4‐h urine collections using liquid chromatography‐mass spectrometry. Results: In CYP2D6 extensive metabolizers, the urinary dextrorphan (DX)/DM metabolic ratio (MR) (CYP2D6 activity marker) was numerically, but not significantly, lower with isotretinoin administration compared to pre‐isotretinoin (geometric mean ratio [GMR] [90% confidence interval (CI)] 0.78 [0.55, 1.11]). The urinary 3‐hydroxymorphinan (3HM)/DX MR (CYP3A activity marker) was increased (GMR 1.18 [1.03, 1.35]) and the urinary DX‐O‐glucuronide/DX MR (proposed UGT2B marker) was increased (GMR 1.22 [1.06, 1.39]) with isotretinoin administration compared to pre‐isotretinoin. Conclusions: Administration of isotretinoin did not significantly reduce CYP2D6 activity in extensive metabolizers, suggesting that the predicted downregulation of CYP2D6 based on in vitro data does not translate into humans. We observed a modest increase in CYP3A activity (predominantly CYP3A4) with isotretinoin treatment. The data also suggest that DX glucuronidation is increased following isotretinoin administration. [ABSTRACT FROM AUTHOR]

Series arrays of closely spaced, planar long Josephson junctions were demonstrated to be transducers of magnetic flux featuring high-dynamic range, wide-bandwidth, and the capability to operate at cryogenic nitrogen temperatures. By tuning and scaling the geometry of these devices, it is possible to improve their sensitivity to an applied magnetic field and to generate higher voltage responses. Moreover, these devices feature linear voltage responses allowing for the potential of unlocked operation. Herein, we study the flux focusing effect in series arrays of planar Josephson junctions, which are well-suited to fabrication in thin films of the high-transition temperature superconductor YBa 2 Cu 3 O 7 − δ via helium focused ion beam irradiation. We present efforts to characterize the array geometry and properties for magnetic field sensing, with investigations of single Josephson junction behavior and demonstrations of small and large series arrays of Josephson junctions. Furthermore, two-tone spectroscopy is performed to quantify the practical linearity of the voltage response. In this work, a series array of 2640 long Josephson junctions is demonstrated, achieving a sensitivity of 1.7 mV/ μ T and a linear response over a region of 10.6 μ T resulting in a dynamic range of 117 dB while operating at 40 K. [ABSTRACT FROM AUTHOR]

Using logistic regression and neural networks, the aim of this study was to compare model performance when predicting player draft outcome during the 2021 AFL National Draft. Physical testing, in-game movement and technical involvements were collected from 708 elite-junior Australian Rules football players during consecutive seasons. Predictive models were generated using data from 465 players (2017 to 2020). Data from 243 players were then used to prospectively predict the 2021 AFL National Draft. Logistic regression and neural network models were compared for specificity, sensitivity and accuracy using relative cut-off thresholds from 5% to 50%. Using factored and unfactored data, and a range of relative cut-off thresholds, neural networks accounted for 73% of the 40 best performing models across positional groups and data configurations. Neural networks correctly classified more drafted players than logistic regression in 88% of cases at draft rate (15%) and convergence threshold (35%). Using individual variables across thresholds, neural networks (specificity = 79 ± 13%, sensitivity = 61 ± 24%, accuracy = 76 ± 8%) were consistently superior to logistic regression (specificity = 73 ± 15%, sensitivity = 29 ± 14%, accuracy = 66 ± 11%). Where the goal is to identify talented players with draft potential, model sensitivity is paramount, and neural networks were superior to logistic regression. [ABSTRACT FROM AUTHOR]

The uterus is a unique mucosal site where immune responses are balanced to be permissive of a fetus, yet protective against infections. Regulation of natural killer (NK) cell responses in the uterus during infection is critical, yet no studies have identified uterine-specific factors that control NK cell responses in this immune-privileged site. We show that the constitutive expression of IFNε in the uterus plays a crucial role in promoting the accumulation, activation, and IFNγ production of NK cells in uterine tissue during Chlamydia infection. Uterine epithelial IFNε primes NK cell responses indirectly by increasing IL-15 production by local immune cells and directly by promoting the accumulation of a pre-pro-like NK cell progenitor population and activation of NK cells in the uterus. These findings demonstrate the unique features of this uterine-specific type I IFN and the mechanisms that underpin its major role in orchestrating innate immune cell protection against uterine infection. Synopsis: IFNε promotes the accumulation, activation and IFNγ production of NK cells in the uterus through both IL-15-dependent and -independent mechanisms. IFNε-mediated NK cell responses protect against Chlamydia FRT infections. IFNε is produced exclusively by reproductive tract epithelial cells and acts in the uterus to increase IL-15 production by myeloid cells. IFNε and IL-15 production in the uterus increases NK cell haematopoiesis in the bone marrow, increasing NK cell numbers systemically, and NK cell accumulation in the uterus. IFNε acts directly on pre-pro NK cell progenitors in the uterus, promoting their accumulation. IL-15 has no effect on this population. Local production of IFNε in the uterus is required for optimal NK cell activation during infection and IFNε directly increases NK cell CD69 expression ex vivo. IL-15 production downstream of IFNε is responsible for promoting NK cell IFNγ production and cytolytic activity. IFNε and IL-15 co-stimulate and are required in concert for full NK cell function. IFNε promotes the accumulation, activation and IFNγ production of NK cells in the uterus through both IL-15-dependent and -independent mechanisms. IFNε-mediated NK cell responses protect against Chlamydia FRT infections. [ABSTRACT FROM AUTHOR]

Tests of the brain's ability to process complex sounds (central auditory tests) correlate with overall measures of neurocognitive performance. In the low- middle-income countries where resources to conduct detailed cognitive testing is limited, tests that assess the central auditory system may provide a novel and useful way to track neurocognitive performance. This could be particularly useful for children living with HIV (CLWH). To evaluate this, we administered central auditory tests to CLWH and children living without HIV and examined whether central auditory tests given early in a child's life could predict later neurocognitive performance. We used a machine learning technique to incorporate factors known to affect performance on neurocognitive tests, such as education. The results show that central auditory tests are useful predictors of neurocognitive performance and perform as well or in some cases better than factors such as education. Central auditory tests may offer an objective way to track neurocognitive performance in CLWH. [ABSTRACT FROM AUTHOR]

The vastness of the space of possible multicomponent metal alloys is hoped to provide improved structural materials but also challenges traditional, low-throughput materials design efforts. Computational screening could narrow this search space if models for materials stability and desired properties exist that are sufficiently inexpensive and accurate to efficiently guide experiments. Toward this effort, here we develop a method to rapidly assess the thermodynamic stability of a metal alloy composition of an arbitrary number of elements, stoichiometry, and temperature based on density functional theory (DFT) data. In our model, the Gibbs free energy of the solid solution contains binary enthalpy contributions and ideal configurational entropy, whereas only enthalpy is considered for intermetallic competing phases. Compared to a past model for predicting the formation of single-phase high-entropy alloys [M. C. Troparevsky et al., Phys. Rev. X 5, 011041 (2015)], our method is similarly inexpensive, since it assesses enthalpies based on existing DFT data, but less heuristic, more broadly applicable, and more accurate (70%–75%) compared to experiment. [ABSTRACT FROM AUTHOR]

Background: Increased airway NLRP3 inflammasome-mediated IL-1β responses may underpin severe neutrophilic asthma. However, whether increased inflammasome activation is unique to severe asthma, is a common feature of immune cells in all inflammatory types of severe asthma, and whether inflammasome activation can be therapeutically targeted in patients, remains unknown. Objective: To investigate the activation and inhibition of inflammasome-mediated IL-1β responses in immune cells from patients with asthma. Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from patients with non-severe (n = 59) and severe (n = 36 stable, n = 17 exacerbating) asthma and healthy subjects (n = 39). PBMCs were stimulated with nigericin or lipopolysaccharide (LPS) alone, or in combination (LPS + nigericin), with or without the NLRP3 inhibitor MCC950, and the effects on IL-1β release were assessed. Results: PBMCs from patients with non-severe or severe asthma produced more IL-1β in response to nigericin than those from healthy subjects. PBMCs from patients with severe asthma released more IL-1β in response to LPS + nigericin than those from non-severe asthma. Inflammasome-induced IL-1β release from PBMCs from patients with severe asthma was not increased during exacerbation compared to when stable. Inflammasome-induced IL-1β release was not different between male and female, or obese and non-obese patients and correlated with eosinophil and neutrophil numbers in the airways. MCC950 effectively suppressed LPS-, nigericin-, and LPS + nigericin-induced IL-1β release from PBMCs from all groups. Conclusion: An increased ability for inflammasome priming and/or activation is a common feature of systemic immune cells in both severe and non-severe asthma, highlighting inflammasome inhibition as a universal therapy for different subtypes of disease. Key messages: We show systemic immune cells from patients with severe and non-severe asthma have increased sensitivity to NLRP3 inflammasome activation and IL-1β release, with responses correlating with neutrophilic and eosinophilic inflammation. Increased inflammasome-mediated IL-1β release in systemic immune cells is similar in male versus female, and obese versus non-obese, patients, and can be readily suppressed using NLRP3 inflammasome-specific inhibitors, highlighting increased inflammasome responses as a potential therapeutic target. [ABSTRACT FROM AUTHOR]

Background/aims To characterise the morphology, location and functional significance of both macular and extramacular collateral vessels (CVs) in patients with a history of branch retinal vein occlusion (BRVO) using widefield swept-source optical coherence tomography angiography (WF SS OCTA). Methods Patients with a history of BRVO underwent WF SS OCTA testing to acquire 12×12 mm images, which were evaluated for CVs and non-perfusion area (NPA). Region of interest analysis of individual CVs was performed to identify correlations between CV size, depth and retinal location. Mixed effects multivariate regression analyses of factors associated with NPA and visual acuity (VA) were performed. Results Fifty-five CVs were identified in 28 BRVO eyes from 27 patients. CVs were identified in 42.9% (12/28) of eyes with a history of BRVO, and of these, 45.5% (25/55) were extramacular. The majority of CVs (87.3%, 48/55) coursed through both the superficial and the deep capillary plexus (DCP), while a subset (12.7%, 7/55) were strictly superficial. No CVs were found to course strictly through the DCP alone. CV depth increased with distance from the optic disc (p=0.011) and CV size increased with distance from the fovea (p=0.005). There were no statistically significant associations between CVs and NPA, or between CVs and VA. Conclusions WF SS OCTA revealed that a large fraction of CVs that form after BRVO are extramacular, and the morphology of CVs varies as a function of retinal location. Depth-resolved study of CVs may offer valuable insights on the pathophysiological mechanisms leading to the development of macular oedema. [ABSTRACT FROM AUTHOR]

This current and pioneering work aimed to assess the on-road performance of selected hybrid electric vehicles (HEVs) and electric vehicles (EVs) in local urban road conditions following the World Harmonized Light Vehicles Test Procedure (WLTP) and the chase car protocol. An experimental research design was also implemented to investigate the effects of the different payload conditions on vehicle performance, and corresponding drive cycle patterns for the test vehicles were generated from each on-road test. From the series of these on-road tests, it was revealed that there was high variability in speed profiles, and vehicle speed was generally found to be inversely related to payload weight. The variations in the state of charge, fuel fill-up, and fuel and energy parameters exhibited no significant differences in terms of payload conditions. When compared to both the Canada fuel consumption guide and the US fuel consumption guide, the resulting fuel consumption and energy consumption indicated that the Mitsubishi Outlander PHEV and Mitsubishi iMiEV exceeded energy efficiency standards, unlike the Toyota Prius. Meanwhile, in terms of CO2 emissions, all vehicles demonstrated around 40–70% lower emissions compared to conventional vehicles according to the 2023 estimates of the US Environmental Protection Agency. Being the first of its kind in the Philippines, this study on the on-road performance assessments of HEVs and EVs is essential because it provides empirical data on these vehicles' actual performance in everyday driving conditions. The data are important for evaluating the potential to address environmental concerns, promote sustainable transportation solutions, influence consumer adoption, and shape government policies. With ongoing improvements in technology and expanding charging infrastructure, HEVs and EVs are poised for significant adoption in the coming years. [ABSTRACT FROM AUTHOR]

The article focuses on a case study of rhegmatogenous retinal detachment (RRD) in a patient with choroideremia, emphasizing the challenges and surgical management of this condition. Topics include the identification of a single posterior retinal hole using multimodal imaging, successful reattachment of the retina through careful surgical techniques, and the potential role of gene therapy in managing choroideremia.

Primary lung carcinoma or lung cancer (LC) is classified into small-cell or non- small-cell (NSCLC) lung carcinoma. Lung squamous cell carcinoma (LSCC) is the second most common subtype of NSCLC responsible for 30% of all LCs, and its survival remains low with only 24% of patients living for five years or longer post- diagnosis primarily due to the advanced stage of tumors at the time of diagnosis. The pathogenesis of LSCC is still poorly understood and has hampered the development of effective diagnostics and therapies. This review highlights the known risk factors, genetic and epigenetic alterations, miRNA biomarkers linked to the development and diagnosis of LSCC and the lack of therapeutic strategies to target specifically LSCC. We will also discuss existing animal models of LSCC including carcinogen induced, transgenic and xenograft mouse models, and their advantages and limitations along with the chemopreventive studies and molecular studies conducted using them. The importance of developing new and improved mouse models will also be discussed that will provide further insights into the initiation and progression of LSCC, and enable the identification of new biomarkers and therapeutic targets. [ABSTRACT FROM AUTHOR]

Chemotaxis is a fundamental process whereby bacteria seek out nutrient sources and avoid harmful chemicals. For the symbiotic soil bacterium Sinorhizobium meliloti, the chemotaxis system also plays an essential role in the interaction with its legume host. The chemotactic signaling cascade is initiated through interactions of an attractant or repellent compound with chemoreceptors or methyl‐accepting chemotaxis proteins (MCPs). S. meliloti possesses eight chemoreceptors to mediate chemotaxis. Six of these receptors are transmembrane proteins with periplasmic ligand‐binding domains (LBDs). The specific functions of McpW and McpZ are still unknown. Here, we report the crystal structure of the periplasmic domain of McpZ (McpZPD) at 2.7 Å resolution. McpZPD assumes a novel fold consisting of three concatenated four‐helix bundle modules. Through phylogenetic analyses, we discovered that this helical tri‐modular domain fold arose within the Rhizobiaceae family and is still evolving rapidly. The structure, offering a rare view of a ligand‐free dimeric MCP‐LBD, reveals a novel dimerization interface. Molecular dynamics calculations suggest ligand binding will induce conformational changes that result in large horizontal helix movements within the membrane‐proximal domains of the McpZPD dimer that are accompanied by a 5 Å vertical shift of the terminal helix toward the inner cell membrane. These results suggest a mechanism of transmembrane signaling for this family of MCPs that entails both piston‐type and scissoring movements. The predicted movements terminate in a conformation that closely mirrors those observed in related ligand‐bound MCP‐LBDs. [ABSTRACT FROM AUTHOR]

Superconducting tunnel spectroscopy has been used for decades to gather valuable information about the electronic density of states and the energy gap in superconductors. For thin film materials, this has, for the most part, only been possible in directions perpendicular to the substrate. For anisotropic materials like the cuprate superconductors, this has hindered knowledge about the density of states in the a–b plane of the film where superconductivity is strongest. The advent of helium ion beam fabricated planar Josephson junctions has fundamentally changed how we can perform tunnel spectroscopy. In this work, we utilize nanoscale Josephson tunnel junctions orientated along different crystalline directions and report the anisotropy of the superconducting energy gap of cuprates at both the micro- and nanoscale. The smaller nanoelectrodes exhibit more variation that roughly correlates with the granularity of the film. We also observe that the gap energy is inversely proportional to the material's conductivity in the voltage state. [ABSTRACT FROM AUTHOR]

Time demands are among the primary challenges for college student-athletes. They have to attend to classes and study halls as well as athletic-related activities such as training and competition. Both academic and athletic tasks require tremendous amount of time. Thus, it is argued that academics and athletics compete for the student-athletes' attention. This research examined the impact of academic and athletic factors on student-athletes' time use in academics and athletics using a subset of the 2015 United States National Collegiate Athletic Association (NCAA) GOALS data. The relationships of academic identity, school belongingness, athletic identity, and athletic expectations with academic time use and athletic time spent were tested. Differences on the variables of interest according to race, gender, and division level were also investigated. Our findings revealed that academic identity is a positive predictor of academic time use and a negative predictor of athletic time use, while athletic identity is a positive predictor of athletic time spent. We also determined a contrasting influence of athletic expectations in time commitments. Lastly, we likewise found significant effects of race, gender, and division level on the academic and athletic engagements of college athletes. Our findings have implications on the development of programs for athletic department to optimize the academic and athletic experiences of college student-athletes. [ABSTRACT FROM AUTHOR]

The reaction of hydrogen atoms (H) with pyrrole (C4H4NH) in solid para-hydrogen (p-H2) matrices at 3.2 K has been studied by infrared spectroscopy. Upon reaction of the H atoms with pyrrole in p-H2, a new series of lines appeared in the infrared spectrum, and based on secondary photolysis, it was determined that the majority of the new lines belong to two distinct chemical species; these lines are designated as set A and set B. According to quantum–chemical calculations performed at the B3PW91/6–311++G(2d,2p) level, the most likely reactions to occur under low temperature conditions in solid p-H2 are the addition of an H atom to carbon 2 or 3 of C4H4NH to produce the corresponding hydrogen-atom addition radicals (HC4H4NH•). When the lines in sets A and B are compared to the scaled harmonic and anharmonic vibrational infrared stick spectra of these two radicals, the best agreement for set A is with the radical produced by the addition to carbon 3 (2,3-dihydropyrrol-2-yl radical, 3-HC4H4NH•), and the best agreement for set B is with the radical produced by addition to carbon 2 (2,3-dihydropyrrol-3-yl radical, 2-HC4H4NH•). The ratio of the 2-HC4H4NH• to 3-HC4H4NH• radicals is estimated to be 4–5:1, consistent with the smaller predicted barrier height for the H-atom addition to C2. In addition to the assignments of the 2,3-dihydropyrrol-2-yl and 2,3-dihydropyrrol-3-yl radicals, a series of lines that appear upon 455-nm photolysis have been assigned to 1,3-pyrrolenine (2-HC4H4N). [ABSTRACT FROM AUTHOR]