bluuebunny/crossref_metadata_2025 huggingface dataset:
Physics-informed machine learning for optimizing the coating conditions of blade coating
Authors: Song Ryungeun , Eo Sole , Lee Minki , Lee Jinkee
Published: July 2022

Large-scale liquid coating has been used in various industrial fields, such as the fabrication of functional panels or surfaces. Blade coating with continuous liquid supply is a cost-effective method for large-scale coatings. To coat a liquid without defects, it is essential to maintain the coating bead trapped under the blade stably. However, numerous experiments are required to obtain the optimal conditions. We developed a novel strategy for acquiring coating conditions using physics-informed neural networks (PINNs) to avoid this laborious effort. Although standard neural networks (NNs) predict the coating performance directly from the operating parameters, PINNs predict parameters related to the state of coating bead to enhance its predictive performance. Our results revealed that the PINNs performed better than the standard NNs. Furthermore, we derived a damped harmonic oscillator model that provides physical insight into the correlation between the coating performance and coating conditions. Finally, a parametric study was performed using the PINN-based model to determine the optimal coating conditional zones, and we experimentally demonstrated the stable coating with the optimized operating parameters.
Experimental investigation on the effect of fluid–structure interaction on unsteady cavitating flows around flexible and stiff hydrofoils
Authors: Lin Yuxing , Kadivar Ebrahim , el Moctar Ould , Neugebauer Jens , Schellin Thomas E.
Published: July 2022

We experimentally investigated the effect of fluid–structure interaction on unsteady cavitating flows around flexible and stiff National Advisory Committee for Aeronautics 0015 hydrofoils in a low-pressure cavitation tunnel. We analyzed the cavitating dynamics by capturing the cavitation dynamics using two high-speed cameras at different cavitating regimes on the surface of the hydrofoils, made of polyvinyl chloride, brass, and aluminum. We then measured the associated structural deformations in specific cavitation regime such as cloud and partial cavitation dynamics, using a digital image correlation technique. The hydrofoil's angle of attack was set to 10°, and the flow's Reynolds number was adjusted to 0.6 × 106. Results showed that the cavity's shedding frequency on the flexible hydrofoil shifted faster to a higher frequency than on the stiff hydrofoils under similar cavitating conditions. The flexible hydrofoil underwent strong structural oscillations at the low cavitation number for the cloud cavitation regime. The associated amplitudes of the vibration were about 20 times higher than those of the hydrofoil made of brass. It was observed that the fluid–structure interaction can significantly affect the cavitation-induced vibration of the flexible hydrofoil.
Analytical and numerical investigation of Poiseuille flow through semi-elliptic annulus
Authors: Kundu K. , Sarkar U. K.
Published: July 2022

A fully developed laminar flow through semi-elliptic annulus formed between two confocal elliptical ducts, driven by a constant pressure-gradient, has been analyzed. The elliptic cylindrical coordinate system has been used to determine the exact solutions for “wide” and “narrow” semi-elliptic annuli with cross sections being symmetric about the minor and major axes of the confocal elliptic boundaries, respectively. For both configurations, exact analytical expressions have been obtained for velocity distribution, volume flow rate, shear stress, and Poiseuille number. The results are expressed in terms of two non-dimensional physical parameters: the ratio of the length of the semi-minor axis to the semi-major axis of the outer boundary, ro, 0 ≤ro<1, and the ratio of the length of semi-major axes of inner and outer elliptic boundaries, rma, c ≤rma<1, with c being the non-dimensional focal distance of the elliptic boundaries. Based on the analytical expressions, the graphical and tabulated results of the flow fields are presented for representative values of ro and rma to illustrate the characteristic features of the flow. Numerical evaluation of the analytical expressions shows that the flow field and the corresponding distributions of velocity and shear stresses are characteristically different for wide and narrow semi-elliptic annuli. In addition to the analytical results, a bivariate Chebyshev pseudospectral method is formulated in the elliptic-cylindrical coordinate system for obtaining the numerical solution of the problem. The numerical results show that the proposed method yields “exponential convergence” or “infinite order of accuracy,” as expected from a spectral method; exact agreement has been observed between the analytical and numerical results.
Prediction of homogeneous isotropic turbulence modulation by small and heavy particles
Authors: Lee Hoonsang , Hwang Wontae
Published: July 2022

In this Letter, we propose a predictive model for the modification of turbulence kinetic energy (TKE) and dissipation rate in isotropic turbulence due to the addition of small and heavy particles. The development of such a model is important for understanding the factors that influence particle–turbulence interactions. Turbulence statistics in the pre-unladen state and physical properties of the particles are input parameters. The model is validated using previous experimental studies conducted under various conditions, and the modification trends of TKE and dissipation rate are predicted fairly well. The effect of the model coefficients on the accuracy of the results is discussed, and it is expected that subsequent experimental studies can improve the model by providing additional guidance for these coefficients.
Pathogen exposure misclassification can bias association signals in GWAS of infectious diseases when using population-based common controls
Authors: Duchen Dylan , Vergara Candelaria , Thio Chloe L. , Kundu Prosenjit , Chatterjee Nilanjan , Thomas David L. , Wojcik Genevieve L. , Duggal Priya
Published: July 2022

Genome-wide association studies (GWAS) have been performed to identify host genetic factors for a range of phenotypes, including for infectious diseases. The use of population-based common controls from biobanks and extensive consortiums is a valuable resource to increase sample sizes in the identification of associated loci with minimal additional expense. Non-differential misclassification of the outcome has been reported when the controls are not well-characterized, which often attenuates the true effect size. However, for infectious diseases the comparison of cases to population-based common controls regardless of pathogen exposure can also result in selection bias. Through simulated comparisons of pathogen exposed cases and population-based common controls, we demonstrate that not accounting for pathogen exposure can result in biased effect estimates and spurious genome-wide significant signals. Further, the observed association can be distorted depending upon strength of the association between a locus and pathogen exposure and the prevalence of pathogen exposure. We also used a real data example from the hepatitis C virus (HCV) genetic consortium comparing HCV spontaneous clearance to persistent infection with both well characterized controls, and population-based common controls from the UK Biobank. We find biased effect estimates for known HCV clearance-associated loci and potentially spurious HCV clearance-associations. These findings suggest that the choice of controls is especially important for infectious diseases or outcomes that are conditional upon environmental exposures.
Epidemiology of Inflammatory Bowel Disease in a Cohort of US Black Women
Authors: Anyane-Yeboa Adjoa , Buadu Maame Araba E. , Khalili Hamed , Cozier Yvette
Published: July 2022

Background and Aims

Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn’s disease are inflammatory diseases of the gastrointestinal tract. The incidence of IBD is increasing in minority populations; however, little is known about the epidemiology and disease characteristics of IBD in Black women.

Methods

Our study population included participants in the Black Women’s Health Study. Diagnosis of IBD was self-reported through the biennial questionnaires starting at baseline in 1995. We estimated the incidence of IBD according to age and geographic region. A follow up supplementary questionnaire was also sent to a subset of participants who reported diagnosis of IBD to evaluate the accuracy of self-reported diagnosis and to assess disease characteristics.

Results

Through December 31st 2021, a total of 609 cases of IBD were reported, of which 142 were prevalent at baseline (prevalence = 0.24%) and 467 were incident (crude incidence rate = 33.2/100, 000 person-years). The incidence of IBD was highest in the <30 years age group and similar across geographic region. Among the participants who responded to the supplementary questionnaire, 62.1% had confirmed diagnosis of IBD.

Conclusions

In a large prospective cohort of US Black women, we found that the incidence of IBD was similar to previously published estimates in US White women. Future studies should focus on identifying risk factors for IBD in Black individuals in the US.

What You Need to Know

Background

The incidence of IBD is increasing in minorities.

Findings

The prevalence and incidence of IBD in the BWHS are higher than previously reported in other cohort studies and similar to those reported in US White women.

Implications for Patient Care

The burden of IBD in US Black women is high and similar to that of US White women.
Shifting PrEP Initiation from Practitioner to Nurse: a clinic-level multi-modal intervention protocol to increase PrEP uptake among women at increased risk of HIV acquisition in a U.S. OB/GYN clinical setting
Authors: Gingher Erin L. , Fruhauf Timothee F. , Sao Saumya S. , Wang Runzhi , Coleman Jenell S.
Published: July 2022

Women comprise 20% of new HIV diagnoses in the U.S. with 86% attributed to heterosexual contact, but HIV pre-exposure prophylaxis (PrEP) uptake is low. OB/GYN clinics are ideal settings to increase HIV prevention counseling for cisgender women, as patients are more likely to discuss their sexual behavior, undergo sexually transmitted infection screening, and receive risk reduction counseling. Our study will assess the feasibility, acceptability, and effectiveness of a registered nurse (RN)-led PrEP project in OB/GYN clinics. Microlearning and Plan-Do-Study-Act cycles will be performed, followed by a randomized controlled trial (RCT). A total of cisgender women determined to be at-risk for HIV will be randomized to standard of care with electronic medical record enhancements (e-SOC) or e-SOC with contact and PrEP counselling by an RN, who will be able to prescribe PrEP under protocol guidance. By shifting HIV PrEP counselling to a nurse, clinics may be able to increase PrEP awareness and uptake.

Registered with clinicaltrials.gov: NCT05095818
The national, longitudinal NASCITA birth cohort study: prevalence of overweight or obesity at 12 months of age in children born healthy
Authors: Clavenna Antonio , Morabito Eleonora , Cartabia Massimo , Campi Rita , Pandolfini Chiara , Bonati Maurizio ,   the NASCITA Working Group
Published: July 2022

Objective

To estimate the prevalence of overweight/obesity at 12 months in an Italian birth cohort and to identify factors related to an increased likelihood of being overweight.

Methods

The Italian NASCITA birth cohort was analysed. Infants were classified as underweight (<5th), normal weight (5th-85th), and overweight (>85th centile) at 12 months of age according to the World Health Organization percentiles of body mass index and the prevalence of overweight/obesity was estimated. To test the association between the chance of being overweight/obese and parental and newborn characteristics, and infant feeding, healthy newborns (no preterm/low birth weight, and with no malformations), with appropriate-for-gestational-age birth weight were selected, and univariate and multivariate analyses were performed

Results

The prevalence of overweight was 23.5% (95%CI 22.2-24.8) in the 4,270 neonates followed during their first year of life, and 23.7% (631/2749) in healthy newborns with a birth weight that was appropriate for gestational age.

A big infant appetite (Odds Ratio 4.39, 95%CI: 2.73-7.07), living in southern Italy (OR 1.64, 95%CI: 1.35-2.00) and maternal age <30 years (OR 1.39, 95%CI: 1.05-1.83) were the main variables associated with a greater likelihood of being overweight/obese. Exclusive breastfeeding for at least 6 months did not influence the chance of being overweight.

Conclusions

The sociodemographic factors (e.g. area of residence, age) seem to be the most relevant determinants influencing the chance of being overweight. In order to prevent childhood and adult obesity, early interventions should be set up or improved, with particular attention to vulnerable families.
Factors Affecting the Incidence of Stroke at a Young Age: A Philosophical Perspective
Authors: Agustiyaningsih Titik , Nur Rohmah Anis Ika , Azizah Lailatul
Published: July 2022

Recently, stroke is a new trend among the young age group in the range of 15-45 years. One of the main complications of this disease is s physical disability, but it also causes communication disorders, emotional disturbances, pain, sleep disturbances, depression, and dysphagia. All of these signs have a major impact on the productivity of the young age group. This article aims to review literatures related to the factors that influence the incidence of stroke at a young age. This study uses a literature study design from 6 databases, namely: Science Direct, ProQuest, Wiley, Sage Pub and Pubmed research. The search used various keyword combinations with the help of Boolean operators, including: “Young Stroke” OR “Young Adults” AND “Risk Factor” OR “Factor”, combined as MESH terms and keywords, and assessment of article quality using the JBI Cohort Studies Cross-Sectional Studies Cohort studies and Case-Control Studies. There were 19 selected articles were analyzed by adjusting the inclusion criteria, namely articles published in the last year, full text accessible, young stroke patient respondents, and discuss the factors that influence the incidence of stroke at a young age. Based on the results of the review, there are several factors that influence the occurance of stroke at a young age including physical factors with a percentage of 85%, lifestyle factors with a percentage of 55%, psychological factors with a percentage of 15%, sex factors with a percentage of 10% and age factors. as much as 5%. Implications in clinical practice include providing psychoeducation as a preventive measure to reduce the incidence of stroke at a young age.
Effects of a feedback intervention on antibiotic prescription control in primary care institutions based on depth graph neural network technology: a cluster randomized cross-over controlled trial
Authors: Yang Junli , Cui Zhezhe , Liao Xingjiang , He Xun , Yu Shitao , Du Wei , Wu Shengyan , Chang Yue
Published: July 2022

Background

Overuse and misuse of antibiotics are major factors in the development of antibiotic resistance in primary care institutions of rural China. In this study, the effectiveness of an artificial intelligence (AI)-based, automatic, and confidential antibiotic feedback intervention was evaluated to determine whether it could reduce antibiotic prescribing rates and avoid inappropriate prescribing behaviors by physicians.

Methods

A randomized, cross-over, cluster-controlled trial was conducted in 77 primary care institutions of Guizhou Province, China. All institutions were randomly divided into two groups and given either a 3-month intervention followed by a 3-month period without any intervention or vice versa. The intervention consisted of 3 feedback measures: a real-time warning pop-up message of inappropriate antibiotic prescriptions on the prescribing physician’s computer screen, a 10-day antibiotic prescription feedback, and distribution of educational brochures. The primary and secondary outcomes are the 10-day antibiotic prescription rate and 10-day inappropriate antibiotic prescription rate.

Results

There were 37 primary care institutions with 160 physicians in group 1 (intervention followed by control) and 40 primary care institutions with 168 physicians in group 2 (control followed by intervention). There were no significant differences in antibiotic prescription rates (32.1% vs 35.6%) and inappropriate antibiotic prescription rates (69.1% vs 72.0%) between the two groups at baseline (p = 0.085, p = 0.072). After 3 months (cross-over point), antibiotic prescription rates and inappropriate antibiotic prescription rates decreased significantly faster in group 1 (11.9% vs 12.3%, p < 0.001) compared to group 2 (4.5% vs 3.1%, p < 0.001). At the end point, the decreases in antibiotic prescription rates were significantly lower in group 1 compared to group 2 (2.6% vs 11.7%, p < 0.001). During the same period, the inappropriate antibiotic prescription rates decreased in group 2 (15.9%, p < 0.001) while the rates increased in group 1 (7.3%, p < 0.001). The characteristics of physicians did not significantly affect the rate of antibiotic or inappropriate antibiotic prescription rates.

Conclusion

The conclusion is that artificial intelligence based real-time pop-up of prescription inappropriate warning, the 10-day prescription information feedback intervention, and the distribution of educational brochures can effectively reduce the rate of antibiotic prescription and inappropriate rate.

Trial registration

ISRCTN, ID: ISRCTN13817256. Registered on 11 January 2020
Fesoterodine ameliorates autonomic dysreflexia while improving lower urinary tract function and urinary incontinence-related quality of life in individuals with spinal cord injury: A prospective phase IIa study
Authors: Walter Matthias , Ramirez Andrea L. , Lee Amanda H. X. , Nightingale Thomas E. , Rapoport Daniel , Kavanagh Alex , Krassioukov Andrei V.
Published: July 2022

The aim of this prospective phase IIa, open-label exploratory, pre-post study was to determine the efficacy of fesoterodine to ameliorate autonomic dysreflexia (AD) in individuals with chronic SCI (>1-year post-injury) at or above the sixth thoracic spinal segment, with confirmed history of AD and neurogenic detrusor overactivity (NDO). We screened 20 individuals. Fifteen individuals provided written informed consent and were assigned to undergo urodynamics, 24-hour ambulatory-blood-pressure-monitoring (ABPM), and urinary incontinence-related quality of life (QoL) measures at baseline and on-treatment. The Montreal Cognitive Assessment (MoCA) and Neurogenic Bowel Dysfunction (NBD) score were used to monitor cognitive and bowel function, respectively. Twelve participants (4 females, median age 42 years) completed this study. Compared to baseline, fesoterodine improved lower urinary tract (LUT) function, i.e., increased cystometric capacity (205 vs 475mL, p = 0.002) and decreased maximum detrusor pressure (44 vs 12cmH2O, p = 0.009). NDO was eliminated in seven (58%) participants. Severity of AD events during urodynamics (40 vs 27mmHg, p = 0.08) and 24-hour ABPM (59 vs. 36mmHg, p = 0.05) were both reduced, yielding a large effect size (r = -0.58). AD Frequency (14 vs. 3, p = 0.004) during 24-hour ABPM was significantly reduced. Urinary incontinence-related QoL improved (68 vs. 82, p = 0.02), however, cognitive (p = 0.2) and bowel function (p = 0.4) did not change significantly. In conclusion, fesoterodine reduces the magnitude and frequency of AD, while improving LUT function and urinary incontinence-related QoL in individuals with chronic SCI without negatively affecting cognitive or bowel function.
My Early Relational Trust-Informed Learning (MERTIL) for Parents: A study protocol for a brief, universal, online, preventative parenting program to enhance relational health
Authors: Opie Jessica , Hooker Leesa , Gibson Tanudja , McIntosh Jennifer
Published: July 2022

Background

Early relational health is a key determinant of childhood development, while relational trauma in the parent-infant dyad can instigate a cascading pattern of infant risk. Fortunately, early relational trauma is detectable and modifiable. In 2018, Australian Maternal and Child Health (MCH) nurses participated in MERTIL (My Early RelationalTrauma-Informed Learning), a program to identify and prevent relational trauma. Program evaluations revealed nurses felt competent and confident to identify and respond to relational trauma; however, response capacity was inhibited by inadequate parent referral options. In response, MERTILfor Parents(My Early RelationalTrust-Informed Learning) was developed, which is an online, evidence-based, self-paced parenting program that focuses on enhancing parental knowledge of relational trust and its significance for infant development. This low-cost, accessible prevention resource targets emerging relational concerns to reduce later service system engagement. The potential for universal preventative online programs that target parental and relational wellbeing remains under-explored. This paper reports on a protocol for implementing a MERTILfor Parentspilot study describing nurses’ and parents’ perspectives on program feasibility and efficacy.

Methods

This study is a mixed-methods, parallel-armed, uncontrolled, repeated measures design. We aim to recruit 48 Australian MCH nurses from the states of Victoria and New South Wales. These nurses will in turn recruit 480 parents with a child aged 0-5 years. All parents will receive MERTILfor Parents, which entails a 40-minute video, tipsheets, worksheets, and support resources. Parent data will be obtained at three periods: pre-program, program exit, and program follow-up. Nurse data will be collected at two periods: parent recruitment completion and program follow-up. Data collection will occur through surveys and focus groups. Primary parent outcomes will be socioemotional assessments of program efficacy. Nurses and parents will each report on study program feasibility.

Discussion

This protocol describes the feasibility and efficacy of a new online parenting program, MERTILfor Parents, with pilot field studies commencing in August 2022. We anticipate that this resource will be a valuable addition to various child and family services, for use in individual support and group work.
Multifaceted effects of bycatch mitigation measures on target/non-target species for pelagic longline fisheries and consideration for bycatch management
Authors: Ochi Daisuke , Okamoto Kei , Ueno Shintaro
Published: July 2022

The pelagic longline fishery, in an effort to reduce bycatch of sea turtles, have developed and deployed fisheries bycatch mitigation techniques such as replacing J/tuna hooks and squid bait with circle hooks and whole fish bait. However, little emphasis has been placed on the side effects of bycatch mitigation measures on endangered species other than target bycatch species. Several previous studies of the side effects have been marred by lack of control for the covariates. Here, based on long-term data obtained from research cruises by a pelagic longline vessel, we examined the effects of using circle hooks and whole fish bait to replace squid bait on the fishing mortality of target and non-target fishes, and also bycatch species. A quantitative evaluation analysis of our results, based on a Bayesian approach, showed the use of circle hooks to increase mouth hooking in target and bycatch species, and their size to be proportional to the magnitude of the effect. While deploying circle hooks did not increase fishing mortality per unit effort (MPUE) for shortfin mako sharks, combining to whole fish bait had a significant increase on MPUE. Because the impact of the introduction of bycatch mitigation measures on species other than the focused bycatch species is non-negligible, a quantitative assessment of bycatch mitigation-related fishing mortality is critical before introducing such measures.
Assessment of COVID-19 hospitalization risk during SARS-CoV-2 Omicron relative to Delta variant predominance, New York City, August 2021–January 2022
Authors: Greene Sharon K. , Levin-Rector Alison , Luoma Elizabeth , Amin Helly , McGibbon Emily , Mathes Robert W. , Ahuja Shama D.
Published: July 2022

Importance

Assessing relative disease severity of SARS-CoV-2 variants in populations with varied vaccination and infection histories can help characterize emerging variants and support healthcare system preparedness.

Objective

To assess COVID-19 hospitalization risk for patients infected with Omicron (BA.1 and sublineages) compared with Delta SARS-CoV-2 variants.

Design

Observational cohort study.

Setting

New York City Department of Health and Mental Hygiene population-based COVID-19 disease registry, linked with laboratory results, immunization registry, and supplemental hospitalization data sources.

Participants

New York City residents with positive laboratory-based SARS-CoV-2 tests during August 2021–January 2022. A secondary analysis restricted to patients with whole-genome sequencing results, comprising 1%–18% of weekly confirmed cases.

Exposures

Diagnosis during periods when ≥98% of sequencing results were Delta (August–November 2021) or Omicron (January 2022). A secondary analysis defined variant exposure using patient-level sequencing results.

Main outcomes and measures

COVID-19 hospitalization, defined as a positive SARS-CoV-2 test 14 days before or 3 days after hospital admission.

Results

Among 646,852 persons with a positive laboratory-based SARS-CoV-2 test, hospitalization risk was lower for patients diagnosed when Omicron predominated (16,025/488,053, 3.3%) than when Delta predominated (8,268/158,799, 5.2%). In multivariable analysis adjusting for demographic characteristics and prior diagnosis and vaccination status, patients diagnosed when Omicron relative to Delta predominated had 0.72 (95% confidence interval [CI]: 0.63, 0.82) times the hospitalization risk. In a secondary analysis of 55,138 patients with sequencing results, hospitalization risk was similar for patients infected with Omicron (2,042/29,866, 6.8%) relative to Delta (1,780/25,272, 7.0%) and higher among those who received two mRNA vaccine doses (adjusted relative risk 1.64, 95% CI: 1.44, 1.87).

Conclusions and relevance

Illness severity was lower for patients diagnosed when Omicron (BA.1 and sublineages) relative to Delta predominated. This finding was consistent after adjusting for prior diagnosis and vaccination status, suggesting intrinsic virologic properties, not population-based immunity, accounted for the lower severity. A secondary analysis demonstrated collider bias from the sequencing sampling frame changing over time in ways associated with disease severity. Investing in representative data collection is necessary to avoid bias in assessing relative disease severity as new variants emerge, immunity wanes, and additional COVID-19 vaccines are administered.
Global patterns and drivers of influenza decline during the COVID-19 pandemic
Authors: Bonacina Francesco , Boëlle Pierre-Yves , Colizza Vittoria , Lopez Olivier , Thomas Maud , Poletto Chiara
Published: July 2022

Influenza circulation declined during the COVID-19 pandemic. The timing and extent of decline and its association with interventions against COVID-19 were described for some regions. Here, we provide a global analysis of the influenza decline between March 2020 and September 2021 and investigate its potential drivers. We computed influenza change by country and trimester relative to the 2014-2019 period using the number of samples in the FluNet database. We used random forests to determine important predictors in a list of 20 covariates including demography, weather, pandemic preparedness, COVID-19 incidence, and COVID-19 pandemic response. With a regression tree we then classified observations according to these predictors. We found that influenza circulation decreased globally, with COVID-19 incidence and pandemic preparedness being the two most important predictors of this decrease. The regression tree showed interpretable groups of observations by country and trimester: Europe and North America clustered together in spring 2020, with limited influenza decline despite strong COVID-19 restrictions; in the period afterwards countries of temperate regions, with high pandemic preparedness, high COVID-19 incidence and stringent social restrictions grouped together having strong influenza decline. Conversely, countries in the tropics, with altogether low pandemic preparedness, low reported COVID-19 incidence and low strength of COVID-19 response showed low influenza decline overall. A final group singled out four “zero-Covid” countries, with the lowest residual influenza levels. The spatiotemporal decline of influenza during the COVID-19 pandemic was global, yet heterogeneous. The sociodemographic context and stage of the COVID-19 pandemic showed non-linear associations with this decline. Zero-Covid countries maintained the lowest levels of reduction with strict border controls and despite close-to-normal social activity. These results suggest that the resurgence of influenza could take equally diverse paths. It also emphasises the importance of influenza reseeding in driving countries’ seasonal influenza epidemics.
Genome-wide analysis of genetic pleiotropy and causal genes across three age-related ocular disorders
Authors: Yao Xueming , Yang Hongxi , Han Han , Kou Xuejing , Jiang Yuhan , Luo Menghan , Zhou Yao , Wang Jianhua , Fan Xutong , Wang Xiaohong , Li Mulin Jun , Yan Hua
Published: July 2022

Purpose

Age-related macular degeneration (AMD), cataract, and glaucoma are leading causes of blindness worldwide. Previous genome-wide association studies (GWASs) have revealed a variety of susceptible loci associated with age-related ocular disorders, yet the genetic pleiotropy and causal genes across these diseases remain poorly understood. This study aims to identify genetic pleiotropic genes among AMD, cataract, and glaucoma.

Methods

We leveraged large-scale genetic and observational data from ocular disease GWASs and UK Biobank (UKBB) to investigate correlations among these ocular disorders. We undertook meta-analyses with the largest GWAS summary statistics of these ocular disorders to identify pleiotropic loci. We then comprehensively integrated eye-specific gene expression quantitative loci (eQTLs), epigenomic profiling, and 3D genome data to prioritize causal pleiotropic genes. Pathway enrichment analysis and drug repurposing analysis were also conducted.

Results

We found significant pairwise genetic correlations and consistent epidemiological associations among AMD, cataract, and glaucoma. Cross-disease meta-analysis uncovered seven pleiotropic loci, three of which were replicated in an additional cohort. Integration of variants in pleiotropic loci and multiple single-cell omics data identified that Müller cells and astrocytes were likely causal cell types underlying ocular comorbidity. After the integration with multi-omics data, 15 causal genes were identified. We found that pleiotropic genes were essential in nerve development and eye pigmentation, and targetable by existing drugs for the treatment of single ocular disorder.

Conclusions

These findings will not only facilitate the mechanistic research of ocular comorbidities but also benefit the therapeutic optimization of age-related ocular diseases.
Susceptibility to monkeypox virus infection: seroprevalence of orthopoxvirus in 4 population samples; France, Bolivia, Laos and Mali
Authors: Luciani Léa , Lapidus Nathanaël , Amroun Abdennour , Falchi Alessandra , Souksakhone Chanthala , Mayxay Mayfong , Dubot-Pérès Audrey , Saba Villarroel Paola Mariela , Diarra Issa , Koita Ousmane , Gallian Pierre , de Lamballerie Xavier
Published: July 2022

Europe is experiencing an epidemic of monkeypox virus against a background of limited knowledge of population immunity to orthopoxviruses. We tested antibodies neutralizing vaccinia virus in blood samples from Bolivia (n=601), Laos (n=657), Mali (n=255) and France (n=4876). We also tested neutralization of cowpox virus in 4448 French samples, which confirmed extensive cross-immunity between both viruses. Using a cut-off titer of 20, seroprevalence is <1% in Bolivia, <5% in Laos (mainly related to vaccination in the elderly), 17.25% in Mali (related to both smallpox vaccination and the likely natural circulation of orthopoxviruses). In France, neutralizing antibodies are found (but at low prevalence) in age groups supposed to be vaccinated, suggesting both decrease in antibody titer in vaccinated individuals and decline in smallpox vaccine compliance before the end of compulsory vaccination. We conclude that the populations tested in Europe, Africa, Asia and South-America are massively susceptible to orthopoxvirus (e.g. monkeypox) infections.

Article summary line

Seroprevalence of orthopoxvirus tested on 4 continents is very low, even for people born before the eradication of smallpox, making populations vulnerable to the emergence of zoonotic orthopoxviruses such as monkeypox virus.
Differential symptoms among COVID-19 outpatients before and during periods of SARS-CoV-2 Omicron variant dominance in Blantyre, Malawi: a prospective observational study
Authors: Chibwana Marah G. , Thole Herbert W. , Anscombe Cat , Ashton Philip M. , Green Edward , Barnes Kayla G. , Cornick Jen , Turner Ann , Witte Desiree , Nthala Sharon , Thom Chikondi , Kanyandula Felistas , Ainani Anna , Mtike Natasha , Tambala Hope , N’goma Veronica , Mwafulirwa Dorah , Asima Erick , Morton Ben , Gmeiner Markus , Gundah Zaziwe , Kawalazira Gift , French Neil , Feasey Nicholas , Heyderman Robert S. , Swarthout Todd D , Jambo Kondwani C.
Published: July 2022

Background

It is widely reported that the SARS-CoV-2 Omicron variant has resulted in high number of cases, but relatively low incidence of severe disease and deaths, compared to the pre-Omicron variants of concern. We aim to assess the differences in symptom prevalence between Omicron and pre-Omicron infections in a sub-Saharan African population.

Methods

In this cross-sectional observational study, we collected data from children and adult outpatients presenting at two primary healthcare facilities in Blantyre, Malawi. Eligible participants were aged >1month old, with signs suggestive of COVID-19, and those not suspected of COVID-19. Nasopharyngeal swabs were collected for SARS-CoV-2 PCR testing and positive samples whole genome sequenced to identify the infecting variant. The primary outcome was the likelihood of presenting with a given symptom in individuals testing positive during the period in which Omicron-dominated (December 2021 to March 2022) with those infected during the pre-Omicron period (August 2021 to November 2021).

Findings

Among 5176 study participants, the median age was 28 years (IQR 21-38), of which 6.4% were under 5, 9.2% were 6 to 17 years, 77% were 18 to 50 years, and 7.1% were above 50 years old. Prevalence of SARS-CoV-2 infection was 23% (1187/5188), varying over time, with peaks in January 2021, July 2021 and December 2021, driven by the Beta (B.1.351), Delta (B.1.617.2) and Omicron (BA.1/2) variants, respectively. Headache (OR 0.47[CI 0.29 – 0.79]), cough (OR 0.37[CI 0.22 – 0.61]), fatigue (OR 0.20[CI 0.08 – 0.48]) and abdominal pain (OR 0.38[CI 0.18 – 0.78]) were less common in participants infected during the Omicron-dominant period than during pre-Omicron period. Fever was more common in participants infected during the Omicron-dominated period than during pre-Omicron period (OR 2.46[CI 1.29 – 4.97]). COVID-19 vaccination, accounting for number of doses and days since last dose, was not associated with a reduced risk of PCR-confirmed SARS-CoV-2 infection (1 dose, OR 1.10[CI 0.39 – 2.66]; 2 doses, OR 1.11[CI 0.40 – 2.57]; all p=0.8).

Interpretation

In this Malawian population, the prevalence of clinical symptoms associated with Omicron infection differ from those of pre-Omicron infections and may be harder to identify clinically with current symptom guidelines. To maintain robust surveillance for COVID-19 and emerging variants, case definitions and testing policies will need to be regularly reviewed to ensure case ascertainment.
From The Plague Horrors of Cholera, What Partnership Lessons Can Be Learnt in Addressing COVID-19 in Zambia
Authors: Chota Pevious , Matenga Tulani Francis L. , Zulu Joseph Mumba , Mweemba Oliver
Published: July 2022

Since the outbreak of COVID-19 on 31 December 2019, different public health systems have been grappling with how to address the spread of the virus. During the cholera outbreak and the Covid-19 pandemic in Zambia, values such as equity, partnership and collaboration have been recognized as central to resilience and an effective response to the pandemic. In this study we identify lessons that can be used for addressing the COVID-19 pandemic from partnership approach used in confronting the cholera outbreak of 2017-2018 in Zambia, Chipata Compound.

Method

Data was collected using a qualitative approach; 26 interviews were conducted with Public Health Professionals and community Leaders. Document reviews from government institutions and non-government institutions were also conducted. The Bergen model of Collaborative Functioning was used to guide the analysis of data.

Results

A top-down approach was observed to be important in addressing cholera but there was a need to improve a bottom-up approach. Synergistic results, avoidance of duplication, Oral cholera vaccination intervention and collaborative capacity building. Challenges in the partnership collaboration included inadequate resources, poor communication, poor coordination, lack of clear shared vision, reactive response, poor involvement of the community, hegemonic powers and mistrust and resentment

Conclusion

From the experience of cholera outbreaks, partnerships are vital in addressing pandemics. Based on the lessons from the cholera outbreaks, we note that there is a need to improve collaboration in partnership if COVID-19 and cholera are to be effectively addressed.
Clinical outcomes of antimicrobial resistance in cancer patients: A systematic review of multivariable models
Authors: Danielsen Anders Skyrud , Franconeri Léa , Page Samantha , Myhre Anders Eivind , Tornes Ragnhild Agathe , Kacelnik Oliver , Bjørnholt Jørgen Vildershøj
Published: July 2022

Background

Infections are major causes of disease in cancer patients and pose a major obstacle to the success of cancer care. The global rise of antimicrobial resistance threatens to make these obstacles even greater and hinder continuing progress in cancer care. To prevent and handle such infections, better multivariable models building on current knowledge are needed. This internally funded systematic review (PROSPERO registration: CRD42021282769) aimed to review multivariable models of resistant infections/colonisations and corresponding mortality, what risk factors have been investigated, and with what methodological approaches.

Methods

We employed two broad searches of antimicrobial resistance in cancer patients, using terms associated with antimicrobial resistance, in MEDLINE and Embase through Ovid, in addition to Cinahl through EBSCOhost and Web of Science Core Collection. Primary, observational studies in English from January 2015 to November 2021 on human cancer patients that explicitly modelled infection/colonisation or mortality associated with antimicrobial resistance in a multivariable model were included. We extracted data on the study populations and their malignancies, risk factors, microbial aetiology, and methods for variable selection, and assessed the risk of bias using the NHLBI Study Quality Assessment Tools.

Results

Two searches yielded a total of 27151 unique records, of which 144 studies were included after screening and reading. Of the outcomes studied, mortality was the most common (68/144, 47%). Forty-five per cent (65/144) of the studies focused on haemato-oncological patients, and 27% (39/144) studied several bacteria or fungi. Studies included a median of 200 patients and 46 events. One-hundred-and-three (72%) studies used a p-value-based variable selection. Studies included a median of seven variables in the final (and largest) model, which yielded a median of 7 events per variable. An in-depth example of vancomycin-resistant enterococci was reported.

Conclusions

We found the current research on this topic to be heterogeneous, in both the methodological and epidemiological approaches. Methodological choices resulting in very diverse models made it difficult or even impossible to draw statistical inferences and summarise what risk factors were of clinical relevance. The development and adherence to more standardised protocols that build on existing literature are urgent.
Clinical Utility of SPECT Neuroimaging in the Diagnosis and Treatment of Traumatic Brain Injury: A Systematic Review
Authors: Hanna Michael , Herman Jaclyn , Zawada Bartosz , Andraos Christine , Karbi Oscar , D’Souza Carina , Kessie Atiemo , Mazengia Getachew , D’Souza Sameer
Published: July 2022

Background

The most common assessment modalities to determine the level of injury following a traumatic brain injury (TBI) includes computerized tomography (CT) scans and/or magnetic resonance imaging (MRI). Evidence is mixed as to whether single photon emission computed tomography (SPECT) is specific and accurate in identifying TBI.

Objectives

This study systematically assessed recent evidence of the clinical utility of SPECT in the diagnosis of TBI and examined the diagnostic accuracy of SPECT in TBI and its performance in comparison to other imaging modalities (e.g., CT and MRI).

Methods

PubMed, MEDLINE, and Embase databases were systematically searched for published articles from December 2012 to July 2022. Randomized controlled trials (RCTs) and observational studies published in English that used SPECT to evaluate patients with all severity of TBIs were eligible for inclusion. Titles and abstracts were screened, and 111 selected full-text articles were independently screened based on predefined inclusion/exclusion criteria (guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses; PRISMA) and assessed for quality using the Newcastle-Ottawa Scale.

Results

Fourteen eligible studies, all observational, reporting location of lesions on brain SPECT were included, reporting data from 21632 participants of which 20,746 participants were from one study; the remaining 886 participants were from the remaining13 studies. The heterogeneity of the data precludes a meta-analysis. There was no consensus among experts from the thirteen smaller studies; however, the largest study indicated that the specificity of visual readings was 54%. In particular, abnormalities and brain perfusions may lead to false positives. Quantitative analysis theoretically increases the reliability of findings for brain SPECT, but error rates are unknown and not published.

Conclusion

There is a lack of evidence to support the clinical utility of brain SPECT for the diagnosis and treatment of TBI.
Implementation of the Liberia National Community Health Assistant (NCHA) Program and Under-five Mortality: A study protocol
Authors: Jockers Dominik , Ngafuan Richard , Baernighausen Till , Kessley Albert , White Emily E. , Kenny Avi , Kraemer John , Geedeh John , Rozelle Jeffrey , Holmes Leah , Obaje Hawa , Wheh Sylvester , Pederson Jon , Siedner Mark J. , Mendin Savior , Subah Marion , Hirschhorn Lisa R
Published: July 2022

Introduction

Between 2018 and 2022 the Liberian Government implemented the National Community Health Assistant (NCHA) program to improve provision of maternal and child health care to underserved rural areas of the country. Whereas the contributions of this and similar community health worker (CHW) based healthcare programs have been associated with improved process measures, the impact of a governmental CHW program at scale on child mortality has not been fully established.

Methods/Design

We will conduct a cluster sampled, community-based survey with landmark event calendars to retrospectively assess child births and deaths among all children born to women in the Grand Bassa District of Liberia. We will use a mixed effects discrete survival model, taking advantage of the staggered program implementation in Grand Bassa districts over a period of 4 years to compare rates of under-5 child mortality between the pre- and post-NCHA program implementation periods.

Discussion

This study will be the first to estimate the impact of the Liberian NCHA program on under-5 mortality.

Trial registration

clinicaltrials.govNCT:NCT05123378
A Phase 2/3 study of S-217622 in participants with SARS-CoV-2 infection (Phase 3 part)
Authors: Yotsuyanagi Hiroshi , Ohmagari Norio , Doi Yohei , Imamura Takumi , Sonoyama Takuhiro , Ichihashi Genki , Sanaki Takao , Tsuge Yuko , Uehara Takeki , Mukae Hiroshi
Published: July 2022

Background

Limited treatment options exist for patients with mild-to-moderate coronavirus disease 2019 (COVID-19), irrespective of vaccination history or risk status. Ensitrelvir is a novel oral severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 3C-like protease inhibitor. While phase 2 studies of ensitrelvir have demonstrated promising results in treating mild-to-moderate COVID-19, evaluation of its clinical efficacy due to shifting vaccination status and emergence of the Omicron variant represents significant challenges. Here, we describe the protocol for a phase 3 study designed to evaluate the efficacy and safety of ensitrelvir in patients with mild-to-moderate COVID-19, regardless of risk status or vaccination history.

Methods

This is a multicenter, randomized, double-blind, placebo-controlled, phase 3 study. Patients with mild-to-moderate COVID-19 within 120 hours from onset will be randomized in a 1:1:1 ratio into 3 treatment arms–ensitrelvir 125 mg (375 mg loading dose on Day 1), ensitrelvir 250 mg (750 mg loading dose on Day 1), and placebo. The study interventions will be administered orally, once daily, for 5 days. The primary endpoint will be the time to resolution of 5 symptoms of COVID-19 (stuffy or runny nose, sore throat, cough, feeling hot or feverish, and low energy or tiredness), and the key secondary endpoints will include the change from baseline on Day 4 in the amount of SARS-CoV-2 viral RNA and the time to first negative SARS-CoV-2 viral titer. The primary population for the primary and key secondary endpoints will be patients with <72 hours from COVID-19 onset to randomization and, subsequently, patients in entire patient population (<120 hours) in the ensitrelvir 125 mg group. Closed testing procedure will be used for the primary and key secondary endpoints in both the primary and entire patient populations. All safety assessments and adverse events will be reported.

Discussion

In a post hoc analysis of the phase 2b study, compared with placebo, ensitrelvir demonstrated a reduced time to resolution of 5 symptoms in patients with mild-to-moderate COVID-19. Through this study, we intend to validate and establish the efficacy and safety of ensitrelvir in patients with mild-to-moderate COVID-19.

Trial registration

Japan Registry of Clinical Trials (https://jrct.niph.go.jp): jRCT2031210350.