bluuebunny/crossref_metadata_2025 huggingface dataset:
Juvenile Xanthogranuloma on the Upper Lip
Authors: Ebisudani Shogo , Suzuki Yoshinori , Osugi Ikuko , Takasu Miori
Published: July 2021

We treated a patient with juvenile xanthogranuloma on the upper lip. A yellow, elastic, hard tumor on the upper lip was evident from birth, which gradually increased in size. The patient was examined at our department at the age of 7 months, at which time the mass extended from the upper lip to the nasal cavity and measured approximately 1 cm. There was a risk that the mass might obstruct the nasal cavity, and an incisional biopsy was conducted to obtain a definitive diagnosis. In histopathological testing, the patient was diagnosed with a juvenile xanthogranuloma. Part of the mass still remains on the upper lip, but has not increased in size during postoperative monitoring. Juvenile xanthogranuloma on the upper lip is extremely rare, and to the best of our knowledge, this is only the fourth case to be reported in the plastic surgery literature in English. In most cases, juvenile xanthogranuloma regresses spontaneously, and unnecessary surgery is to be avoided. The possibility of juvenile xanthogranuloma should always be considered for masses that increase in size in infants and young children, and it is important to reach a definitive diagnosis by skin biopsy.
Using Structural Empowerment to Improve Outcomes
Authors: Newberry Lynn W.
Published: July 2021

In the changing healthcare climate, a robust continuous professional development program is critical to ensure excellent patient care and the best outcomes. It is essential for educators and leaders to understand the factors that enhance the impact of continuous professional development. Organizational leadership must support successful education programs and the ability to provide educational activities. In this month's Magnet® Perspectives, we will review how the Institute of Medicine and Quadruple Aim framework can support structural empowerment through continuous professional development to improve outcomes.
A Longitudinal Study of the Impact of Schwartz Center Rounds on Moral Distress
Authors: Whitehead Phyllis B. , Locklear Tonja M. , Carter Kimberly Ferren
Published: July 2021

Moral distress occurs when moral integrity is compromised and can affect any healthcare professional. This study examined the impact of Schwartz Center Rounds (SCRs) on moral distress using a longitudinal, quasi-experimental design to examine SCR attendees from 2015 to 2019. Data were collected via a 2-part survey composed of demographics and Moral Distress Thermometer (MDT) readings before rounds and immediately after rounds. Most participants experienced either no change in moral distress (50.6%) or a decrease in moral distress (33.7%) after attending one of the SCRs. Participants who worked with adult populations had higher moral distress after participation for most topics. An increase in moral distress was associated with a longer time in the current position. Fifty percent of the physicians had a decrease in their moral distress immediately after the rounds. Schwartz Center Rounds is a promising approach to foster high-functioning teams while promoting wellness and mitigating moral distress among employees.
Nonvaccine human papillomavirus genotype common in women with HIV failing cervical precancer treatment
Authors: Carlander Christina , Lagheden Camilla , Eklund Carina , Nordqvist Kleppe Sara , Dzabic Mensur , Wagner Philippe , Sparén Pär , Dillner Joakim
Published: July 2021

Objective:

The aim of this study was to assess failure after treatment of high-grade cervical intraepithelial neoplasia (CIN2+) by HIV status and human papillomavirus (HPV) type.

Design:

A population-based register study.

Methods:

The Swedish National HIV Registry, the Swedish Population Registry and the Swedish National Cervical Screening Registry were linked to identify all women in Stockholm and Gothenburg counties (Sweden) living with HIV and diagnosed with CIN2+ sometime between 1983 and 2014 (n = 179). HIV-negative controls with CIN2+, were matched (2 : 1) for country of birth. CIN2+ biopsies were retrieved from biobanks and genotyped. Absolute risk and adjusted odds ratios (adjOR) of treatment failure by HIV status given HPV type (HPV16/18 vs. non-HPV16/18) were calculated.

Results:

HPV16 (32%) and HPV35 (24%) dominated in women living with HIV (WLWH) with failure, HPV35 mainly in women born in sub-Saharan Africa (67%). The absolute risk of failure in women with HPV16/18 was 26% [95% confidence interval (95% CI) 14–44] in WLWH and 12% in HIV-negative (95% CI 7–19). The absolute risk of failure in women with non-HPV16/18 was 20% (95% CI 12–31) in WLWH and 5% in HIV-negative (95% CI 2–11). WLWH with non-HPV16/18 were six times more likely to fail than HIV-negative (adjOR 6.1, 95% CI 2.0–18.6).

Conclusion:

HPV35, not included in current HPV vaccines, was the second most common type in WLWH with failure. WLWH with non-HPV16/18 were six times more likely to fail than HIV-negative. This could have implications for surveillance and vaccination post CIN2+ treatment, particularly in WLWH from sub-Saharan Africa.
Nucleation and growth dynamics of ellipsoidal crystals in metastable liquids
Authors: Nikishina Margarita A. , Alexandrov Dmitri V.
Published: July 2021

When describing the growth of crystal ensembles from metastable solutions or melts, a significant deviation from a spherical shape is often observed. Experimental data show that the shape of growing crystals can often be considered ellipsoidal. The new theoretical models describing the transient nucleation of ellipsoidal particles and their growth with and without fluctuating rates at the intermediate stage of bulk phase transitions in metastable systems are considered. The nonlinear transport (diffusivity) of ellipsoidal crystals in the space of their volumes is taken into account in the Fokker–Planck equation allowing for fluctuating growth rates. The complete analytical solutions of integro-differential models of kinetic and balance equations are found and analysed. Our solutions show that the desupercooling dynamics is several times faster for ellipsoidal crystals as compared to spherical particles. In addition, the crystal-volume distribution function is lower and shifted to larger particle volumes when considering the growth of ellipsoidal crystals. What is more, this function is monotonically increasing to the maximum crystal size in the absence of fluctuations and is a bell-shaped curve when such fluctuations are taken into account.

This article is part of the theme issue ‘Transport phenomena in complex systems (part 1)’.
Effect of ring-shaped clusters on magnetic hyperthermia: modelling approach
Authors: Abu-Bakr Ali F. , Zubarev Andrey Yu.
Published: July 2021

Experiments demonstrate that magnetic nanoparticles, embedded in a tissue, very often form heterogeneous structures of various shapes and topologies. These structures (clusters) can significantly affect macroscopical properties of the composite system, in part its ability to generate heat under an alternating magnetic field (so-called magnetic hyperthermia). If the energy of magnetic interaction between the particles significantly exceeds the thermal energy of the system, the particles can form the closed ring-shaped clusters. In this work, we propose a relatively simple model of the heat production by the particles united in the ‘ring’ and immobilized in a host medium. Mathematically, this model is based on the phenomenological Debye equation of kinetics of the particles remagnetization. Magnetic interaction between all particles in the cluster is taken into account. Our results show that the appearance of the clusters can significantly decrease the thermal effect.

This article is part of the theme issue ‘Transport phenomena in complex systems (part 1)’.
On the forecastability of food insecurity
Authors: Foini Pietro , Tizzoni Michele , Martini Giulia , Paolotti Daniela , Omodei Elisa
Published: July 2021

Food insecurity, defined as the lack of physical or economic access to safe, nutritious and sufficient food, remains one of the main challenges included in the 2030 Agenda for Sustainable Development. Near real-time data on the food insecurity situation collected by international organizations such as the World Food Programme can be crucial to monitor and forecast time trends of insufficient food consumption levels in countries at risk. Here, using food consumption observations in combination with secondary data on conflict, extreme weather events and economic shocks, we build a forecasting model based on gradient boosted regression trees to create predictions on the evolution of insufficient food consumption trends up to 30 days in to the future in 6 countries (Burkina Faso, Cameroon, Mali, Nigeria, Syria and Yemen). Results show that the number of available historical observations is a key element for the forecasting model performance. Among the 6 countries studied in this work, for those with the longest food insecurity time series, that is Syria and Yemen, the proposed forecasting model allows to forecast the prevalence of people with insufficient food consumption up to 30 days into the future with higher accuracy than a naive approach based on the last measured prevalence only. The framework developed in this work could provide decision makers with a tool to assess how the food insecurity situation will evolve in the near future in countries at risk. Results clearly point to the added value of continuous near real-time data collection at sub-national level.
Prospective genomic surveillance reveals cryptic MRSA outbreaks with local to international origins among NICU patients
Authors: Worley Jay N. , Crothers Jessica W. , Wolfgang William J. , Venkata Sai Laxmi Gubbala , Hoffmann Maria , Jayeola Victor , Klompas Michael , Allard Marc , Bry Lynn
Published: July 2021

MRSA infections cause significant morbidity and mortality in neonates. Clinical testing and routine surveillance screening identified an increase in neonates with MRSA colonization and infection which triggered prospective genomic surveillance. Here we show the complex transmission dynamics of MRSA in a NICU setting. Analyses revealed concurrent transmission chains affecting 16 of 22 MRSA-colonized patients (68%), and 3.1% of all NICU patients (n=517). Prematurity and longer lengths of stay increased risks for colonization. Intervals of up to 7 months occurred among some cluster-related isolates. 3 of 22 MRSA-colonized patients developed invasive infections with the colonizing strain. Comparisons with 21,521 isolates in the NCBI Pathogen Detection Resource revealed NICU strains to be distinct from MRSA seen locally and internationally. Integration of international strain datasets in analyses increased the resolution of strain clusters and helped rule-out suspected transmission events. Analyses also identified sequence type 1535 isolates, emergent in the Middle East, carrying a unique SCCmec with fusC and aac(6’)-Ie/aph(2’’)-1a that provided a multi-drug resistant phenotype. NICU genomic surveillance identified cryptic MRSA colonization events, including NICU-endemic strains not linked with local hospital or international clusters, and has rich potential to guide improvements in infection prevention for this vulnerable patient population.
Understanding Adverse Population Sentiment Towards the Spread of COVID-19 in the United States
Authors: Hohl Alexander , Choi Moongi , Medina Richard , Wan Neng , Wen Ming
Published: July 2021

Background

During the ongoing COVID-19 pandemic, the immediate threat of illness and mortality is not the only concern. In the United States, COVID-19 is not only causing physical suffering to patients, but also great levels of adverse sentiment (e.g., fear, panic, anxiety) among the public. Such secondary threats can be anticipated and explained through sentiment analysis of social media, such as Twitter.

Methods

We obtained a dataset of geotagged tweets on the topic of COVID-19 in the contiguous United States during the period of 11/1/2019 - 9/15/2020. We classified each tweet into “adverse” and “non-adverse” using the NRC Emotion Lexicon and tallied up the counts for each category per county per day. We utilized the space-time scan statistic to find clusters and a three-stage regression approach to identify socioeconomic and demographic correlates of adverse sentiment.

Results

We identified substantial spatiotemporal variation in adverse sentiment in our study area/period. After an initial period of low-level adverse sentiment (11/1/2019 - 1/15/2020), we observed a steep increase and subsequent fluctuation at a higher level (1/16/2020 - 9/15/2020). The number of daily tweets was low initially (11/1/2019 - 1/22/2020), followed by spikes and subsequent decreases until the end of the study period. The space-time scan statistic identified 12 clusters of adverse sentiment of varying size, location, and strength. Clusters were generally active during the time period of late March to May/June 2020. Increased adverse sentiment was associated with decreased racial/ethnic heterogeneity, decreased rurality, higher vulnerability in terms of minority status and language, and housing type and transportation.

Conclusions

We utilized a dataset of geotagged tweets to identify the spatiotemporal patterns and the spatial correlates of adverse population sentiment during the first two waves of the COVID-19 pandemic in the United States. The characteristics of areas with high adverse sentiment may be relevant for communication of containment measures. The combination of spatial clustering and regression can be beneficial for understanding of the ramifications of COVID-19, as well as disease outbreaks in general.
Financial burden of Chronic Kidney Disease Patients on Maintenance Hemodialysis in Chittagong, Bangladesh
Authors: Biswas Rajat Sanker Roy , Nath Jishu Deb , Ahmed Kazi Farhad
Published: July 2021

Background

Chronic kidney disease (CKD) is an important public health problem. Renal replacement therapy (RRT) is needed to patients who goes to end stage renal disease(ESRD). Most of the evidence on its costs relates to patients receiving dialysis or kidney trans-plants, which shows that, in these phases, CKD poses a high burden to payers. The aim of this study was to estimate the financial burden of patients with CKD on maintenance hemodialysis.

Methods

It is one -year observational study, carried out to collect data on 105 patients with CKD on dialysis taking from different centers of Chittagong Bangladesh. After collection of sociodemographic informations financial status were collected from patients who gave informed written consent to be included in the study. Data were analyzed by SPSS 20.

Results

Regarding gender distribution, male was 73(69.5%) and female was 32(30.5%). Male to female ratio was 2.28:1. Age group distribution revealed 10(9.5%) patients were at <30 years, 18(17.1%) were at 31-40 years, 23(21.9%) were at 41-50 years, 26(24.8%) were at 51-60 years, 20(19.0%) were at 61-70 years and 8(7.6%) were >71 years age. Among all most were involved in service 40(38.1%) and business 23(21.9%). Socio economic status of the patients revealed 42(40.0%) patients were from upper middle class, 50(47.6%) were from lower middle class. Among all, 33(31.4%) patients took treatment from abroad. Regarding bearing of cost of the dialysis 24(22.9%) were self financed and 35(33.3%) got help from others(non family member), 11(10.5%) took loan and 13(12.4%) sold their stable land property. Regarding tenure of dialysis 31(29.5% patients are getting dialysis <1 year and 74(70.5%) were getting it for 1-2 years. Previous monthly income before start of dialysis was zero(0) in 33(31.4%) patients and it was >30000 taka/month in 34(32.4%) patients and after start of dialysis present monthly income was zero(o) per month in 67(63.8%) patients and >30000 taka/month in 13(12.4%) patients. Regarding expenditure for each dialysis showed 2(1.9%) had zero(0) taka and 46(43.8%) patients needed 1000-2000 taka/session and 41(39.0%) needed 2000-3000 taka /session.

Conclusion

Dialysis in CKD patients is a huge financial burden to the patients himself and the family. Government assistance should be provided to all patients who are unable to bear the cost.
Accelerometer-measured habitual physical activity and sedentary time in pediatric concussion: A controlled cohort study
Authors: Sharma Bhanu , Obeid Joyce , DeMatteo Carol , Noseworthy Michael D. , Timmons Brian W.
Published: July 2021

Objectives

To characterize and quantify differences in accelerometer-measured physical activity and sedentary time between children with concussion (within the first month of injury) and 1:1 matched healthy controls.

Methods

Secondary analysis of accelerometer data collected on 60 children with concussion and 60 healthy controls matched for age, sex, and season of accelerometer wear. Daily and hourly sedentary time, light physical activity (LPA), moderate physical activity (MPA), and vigorous physical activity (VPA) were compared between groups per independent samples t-tests.

Results

Children with concussion (12.74 ± 2.85 years, 31 females) were significantly more sedentary than controls (12.43 ± 2.71 years, 31 females; mean difference [MD], 38.3 minutes/day, p=0.006), and spent less time performing LPA (MD, -19.5 minutes/day, p=0.008), MPA (MD, -9.8 minutes/day, p<0.001), and VPA(MD, -12.0 minutes/day, p<0.001); hour-by-hour analyses showed that these differences were observed from 8:00AM to 9:00PM. Sex-specific analyses identified that girls with concussion were less active and more sedentary than both boys with concussion (MD, 50.8 minutes/day; p=0.010) and healthy girls (MD, 51.1 minutes/day; p<0.010). Days post-injury significantly predicted MPA (β=0.071, p=0.032) and VPA (β=0.095, p=0.004), but not LPA or sedentariness in children with concussion.

Conclusion

Clinical management should continue to advise against prolonged rest following pediatric concussion, given the activity debt observed within the first-month of injury. Currently, clinical management of concussion is shifting towards prescribing a single bout of daily sub-maximal aerobic exercise. Interventions aimed at reducing overall sedentary time and increasing habitual physical activity in pediatric concussion also warrant study.

KEY FINDINGS

What are the new findings?

Per accelerometry, children with concussion are significantly more sedentary than healthy controls within the first-month of injury

Relative to healthy controls, in the first-month of injury, children with concussion perform less accelerometer-measured light, moderate, and vigorous physical activity

These patterns of increased sedentary time and reduced physical activity are seen throughout the day, from 8:00 AM to 9:00 PM

Moderate and vigorous physical activity levels are predicted by days-post injury in children with concussion, and may increase naturally as a consequence of recovery

How might it impact on clinical practice in the future?

Given the accumulating evidence that prolonged rest should be avoided following concussion, primary care clinicians should continue to advocate for light physical activity post-concussion to limit increased sedentary time
Scaling SARS-CoV-2 Wastewater Concentrations to Population Estimates of Infection
Authors: Kaplan Edward H. , Zulli Alessandro , Sanchez Marcela , Peccia Jordan
Published: July 2021

Monitoring the progression of SARS‐CoV‐2 outbreaks requires accurate estimates of infection rates. Estimation methods based on observed cases are biased due to changes in testing over time. Here we report an approach based upon scaling daily concentrations of SARS‐CoV‐2 RNA in wastewater to infections that produces representative estimates due to the consistent population contribution of fecal material to the sewage collection system.
Positive Mental Training in patients with Multiple Sclerosis experiencing psychological distress: A Preliminary Randomised Controlled Trial
Authors: Murray Katy , Melchiorre Giulia , Dobbin Alastair , Welch Killian A
Published: July 2021

Introduction

Psychological distress is a major issue in multiple sclerosis (MS), having a significant impact on quality of life. Antidepressants are generally unhelpful for subsyndromal symptomatology, and psychological treatment approaches often not accessible or too cognitively demanding for some patients. There is an urgent need for low-cost interventions to improve wellbeing in MS.

Methods

This was a pilot randomised controlled trial (RCT) of Positive Mental Training (PosMT), a low intensity intervention providing training in positivity, optimism and resilience previously shown to improve anxious and depressive symptomotology. 28 patients with MS were randomised to the intervention and 30 to the control group.

Results

Follow-up data was obtained from 39 patents. The majority of participants receiving PosMT reported that they had used the intervention, with few reporting side effects. The intervention group reported a significant improvement in self-rated health as measured by the EuroQual visual analogue scale, F(4,34) = 3.204, p = 0.025, R2 = 0.274.

Discussion

This preliminary RCT found that PosMT in its current form could be used by patients with MS with little difficulty. Despite the small size of the study, allocation to the intervention was found to be associated with a significant improvement in self-rated health. Given the low cost of PosMT and its easy availability (it can simply be downloaded from a website), this pilot RCT suggests it could be a useful tool for MS patients. We believe this intervention warrants further study, ideally in a large multi-centre RCT.
Association between willingness to receive the COVID-19 vaccine and sources of health information among Japanese workers: a cohort study
Authors: Hiraoka Ko , Nagata Tomohisa , Mori Takahiro , Ando Hajime , Hino Ayako , Tateishi Seiichiro , Tsuji Mayumi , Matsuda Shinya , Fujino Yoshihisa ,   for the CORoNaWork project
Published: July 2021

Background

It is important to achieve herd immunity by vaccinating as many people as possible to end the COVID-19 pandemic. We investigated the relationship between willingness to receive vaccination and sources of health information among those who did not want to be vaccinated against COVID-19.

Methods

This prospective cohort study collected data using a self-administered questionnaire survey. The baseline survey was conducted during December 22–25, 2020, and the follow-up survey during February 18–19, 2021. Participants were aged 20–65 years and worked at the time of the baseline survey (N = 33,087). After excluding 6,051 invalid responses, we included responses from 27,036 participants at baseline. In total, 19,941 people responded to the follow-up survey (74% follow-up rate). We excluded 7,415 participants who answered “yes” to the question “If a COVID-19 vaccine becomes available, would you like to get it?” in the baseline survey. We finally analyzed 12,526 participants.

Results

The odds ratio for change in willingness to be vaccinated from “no” to “yes” differed by source of health information. Compared with workers that used TV as a source of information, significantly fewer people who reported getting information from the Internet and friends/colleagues were willing to get the vaccine.

Conclusions

It is important to approach workers who do not watch TV when implementing workplace vaccination programs. It is likely that willingness to be vaccinated can be increased through an active company policy whereby the top management recommend vaccination, coupled with an individual approach by occupational health professionals.

Trial registration

Not applicable.
Spontaneous Mutants of Streptococcus sanguinis with Defects in the Glucose-PTS Show Enhanced Post-Exponential Phase Fitness
Authors: Zeng Lin , Walker Alejandro R. , Lee Kyulim , Taylor Zachary A. , Burne Robert A.
Published: July 2021

Genetic truncations in a gene encoding a putative glucose-PTS protein (manL, EIIABMan) were identified in subpopulations of two separate laboratory stocks of Streptococcus sanguinis SK36; the mutants had reduced PTS activities on glucose and other monosaccharides. Using an engineered mutant of manL and its complemented derivative, we showed that the ManL-deficient strain had improved bacterial viability in stationary phase and was better able to inhibit the growth of the dental caries pathogen Streptococcus mutans. Transcriptional analysis and biochemical assays suggested that the manL mutant underwent reprograming of central carbon metabolism that directed pyruvate away from production of lactate, increasing production of hydrogen peroxide (H2O2) and excretion of pyruvate. Addition of pyruvate to the medium enhanced the survival of SK36 in overnight cultures. Meanwhile, elevated pyruvate levels were detected in the cultures of a small, but significant percentage (∼10%), of clinical isolates of oral commensal bacteria. Furthermore, the manL mutant showed higher expression of the arginine deiminase system than the wild type, which enhanced the ability of the mutant to raise environmental pH when arginine was present. Significant discrepancies in genome sequence were identified between strain SK36 obtained from ATCC and the sequence deposited in GenBank. As the conditions that are likely associated with the emergence of spontaneous manL mutations, i.e. excess carbohydrates and low pH, are those associated with caries development, we propose that the glucose-PTS strongly influences commensal-pathogen interactions by altering the production of ammonia, pyruvate, and H2O2.

Importance

A health-associated dental microbiome provides a potent defense against pathogens and diseases. Streptococcus sanguinis is an abundant member of a health-associated oral flora that antagonizes pathogens by producing hydrogen peroxide. There is a need for a better understanding of the mechanisms that allow bacteria to survive carbohydrate-rich and acidic environments associated with the development of dental caries. We report the isolation and characterization of spontaneous mutants of S. sanguinis with impairment in glucose transport. The resultant reprograming of central metabolism in these mutants reduced the production of lactic acid and increased pyruvate accumulation; the latter enables these bacteria to better cope with hydrogen peroxide and low pH. The implications of these discoveries in the development of dental caries are discussed.
Exploring relationships between drought and epidemic cholera in Africa using generalised linear models
Authors: Charnley Gina E C , Kelman Ilan , Green Nathan , Hinsley Wes , Gaythorpe Katy A M , Murray Kris A
Published: July 2021

Background

Temperature and precipitation are known to affectVibrio choleraeoutbreaks. Despite this, the impact of drought on outbreaks has been largely understudied. Africa is both drought and cholera prone and more research is needed in Africa to understand cholera dynamics in relation to drought.

Methods

Here, we analyse a range of environmental and socioeconomic covariates and fit generalised linear models to publicly available national data, to test for associations with several indices of drought and make cholera outbreak projections to 2070 under three scenarios of global change, reflecting varying trajectories of CO2emissions, socio-economic development, and population growth.

Results

The best-fit model implies that drought is a significant risk factor for African cholera outbreaks, alongside positive effects of population, temperature and poverty and a negative effect of freshwater withdrawal. The projections show that following stringent emissions pathways and expanding sustainable development may reduce cholera outbreak occurrence in Africa, although these changes were spatially heterogeneous.

Conclusions

Despite an effect of drought in explaining recent cholera outbreaks, future projections highlighted the potential for sustainable development gains to offset drought-related impacts on cholera risk. Future work should build on this research investigating the impacts of drought on cholera on a finer spatial scale and potential non-linear relationships, especially in high-burden countries which saw little cholera change in the scenario analysis.
HIV Testing Uptake and Late Diagnosis among Urban Population of Ethiopia: A Multilevel Modeling Approach
Authors: Getaneh Yimam , Ayalew Jemal , Abate Ebba , Tayachew Adamu , Lulseged Sileshi , Shao Yiming
Published: July 2021

Background

Expanding HIV testing and early diagnosis requires a better understanding of determinants to uptake and late diagnosis. We investigated factors contributing to HIV testing uptake and late diagnosis.

Objective

The aim of this study was to determine level of HIV Testing Uptake and Late Diagnosis among Urban Population of Ethiopia

Design

We used data from the Ethiopian Population Based HIV Impact assessment in Ethiopia (EPHIA), conducted in 2017/18. EPHIA was a nationally-representative, cross-sectional and household-based study, conducted in urban Ethiopia which used a two-stage cluster sampling design with stratification into small and large urban areas. The EPHIA data were collected from 19,136 adults aged 15 to 64 years. For current study, we considered self-reports first diagnosis to estimate the testing uptake and also consider HIV LAg avidity Vs Viral Load Vs plasma Antiretroviral drug level algorithm to categorize the late diagnosis. In this analysis, a 2-level multilevel mixed-effect logistic regression model was employed using STATA v16. The effects of individual-level predictors were quantified by the estimates from the fixed-effect part of the model with a p-value less than 0.05 or 95% CI.

Result

By the year 2017/18, overall 29.4% of people living with HIV (PLHIV) were never tested in urban Ethiopia. Never tested male was significantly higher (32.4%; 95%: 31.0, 33.9) than females (26.4%; 95%: 25.3, 27.5) while it ranged from 28.3% to 47.8% among 45–54 and 15–24 years, respectively. By the same study period, 25.9% (95% CI: 21.7, 30.2) of PLHIV were lately diagnosed and male was significantly higher (36.8%; 95%: 28.0, 46.6) than females (20.8%; 95%: 17.3, 24.9). Late HIV diagnosis was also heterogeneous by various age group categories. Late diagnosis varies by region which ranged from 38.1% in the Gambella to 5.8% in Benishangul Gumuz. HIV testing uptake and late diagnosis was also significantly affected by alcohol use, income and educational status.

Conclusion

Ethiopia was behind the global target for HIV testing uptake. Late diagnosis of HIV constituted one-quarter of all testing HIV positive, and this was significantly higher among adult males. HIV testing offer and early diagnosis strategy need to focus on addressing geographically highly affected regions, and male and young adolescent age groups. The widowed population group, which is highly affected by HIV, and has low level of testing uptake, may require due attention by the HIV program. It is also suggested that HIV care and treatment programs provide a focus to the disadvantaged populations, especially those with limited education and low income.
Social determinants of health exacerbate disparities in COVID-19 illness severity and lasting symptom complaints
Authors: Thomason Moriah E. , Hendrix Cassandra L. , Werchan Denise , Brito Natalie H.
Published: July 2021

BACKGROUND

Increasing reports of long-term symptoms following COVID-19 infection, even among mild cases, necessitates systematic investigation into the prevalence and type of lasting illness. Notably, there is limited data regarding the influence of social determinants of health, like perceived discrimination and economic stress, which may exacerbate COVID-19 health risks. The primary goals of this study are to test the bearing of subjective experiences of discrimination, financial security, and quality of care on illness severity and lasting symptom complaints.

METHODS

1,584 recovered COVID-19 patients that experienced mild to severe forms of the disease provided information about their illness, medical history, lasting symptoms, and psychosocial information. Prevalence data isolated differences in patients infected early versus late in the pandemic. Path analyses examined hypothesized associations between discrimination, illness severity, and lasting symptoms. Post hoc logistic regressions tested social determinants hypothesized to predict neurological, cognitive, or mood symptoms.

RESULTS

70.6% of patients reported presence of one or more lasting symptoms after recovery. Neural systems were especially impacted, and 19.4% and 25.1% of patients reported mood or cognitive/memory complaints, respectively. Path models demonstrated that frequency and stress about experiences of discrimination predicted increased illness severity and increased lasting symptom count, even when adjusting for sociodemographic factors and mental/physical health comorbidities. Notably, this effect was specific to stress related to discrimination, and did not extend to general stress levels. Further, perceived but not objective socioeconomic status (SES) was associated with increased lasting symptom complaints after recovery. Finally, associations between discrimination and illness differed with individual perceptions about quality of medical care.

CONCLUSIONS

Lasting symptoms after recovery from COVID-19 are highly prevalent and neural systems are significantly impacted. Importantly, psychosocial factors (perceived discrimination and perceived SES) can exacerbate individual health risk. This study provides actionable directions for improved health outcomes by establishing that sociodemographic risk and medical care influence near and long-ranging health outcomes.
Taller height and risk of coronary heart disease and cancer: a within-sibship Mendelian randomization study
Authors: Howe Laurence J , Brumpton Ben , Rasheed Humaira , Åsvold Bjørn Olav , Willer Cristen J , Smith George Davey , Davies Neil M
Published: July 2021

Taller people have lower risk of coronary heart disease but higher risk of many cancers. Mendelian randomization studies in unrelated individuals have suggested that these relationships are potentially causal. However, Mendelian randomization estimates from samples of unrelated individuals are sensitive to demography (population stratification, assortative mating) and familial (indirect genetic) effects. Height could influence disease risk via anatomic and physiological effects of height (e.g., number of cells or the bore of arteries) or previous results may have been confounded by early-life environmental factors (e.g., parental socioeconomic position and nutrition).

In this study, we performed within-sibship Mendelian randomization analyses using 77,757 siblings, a design robust against demography and indirect genetic effects of parents. Within-sibship Mendelian randomization estimated that one SD taller height lowers odds of coronary heart disease by 14% (95% CI: 3% to 23%) but increases odds of cancer by 18% (95% CI: 3% to 34%). There was some evidence that taller height reduces systolic blood pressure and LDL cholesterol, which may mediate some of the protective effect of taller height on coronary heart disease risk.

For the first time, we have demonstrated that purported effects of height on adulthood disease risk are unlikely to be explained by demographic or familial factors, and so likely reflect an individual-level causal effect. Disentangling the mechanisms via which height affects disease risk may improve understanding of the aetiologies of atherosclerosis and carcinogenesis.
Regeneration of Plants from DNA-free Edited Grapevine Protoplasts
Authors: Scintilla Simone , Salvagnin Umberto , Giacomelli Lisa , Zeilmaker Tieme , Malnoy Mickael A. , van der Voort Jeroen Rouppe , Moser Claudio
Published: July 2021

CRISPR-Cas technology has widely extended the application fields of genome editing in plant breeding, making possible specific and minimal mutations within a genetic pool. With respect to standard genome editing technologies, CRISPR-Cas machinery can be introduced in the form of ribonucleoproteins (RNPs), thus avoiding the introduction of exogenous DNA into cells. The interest on the application of DNA-free delivery into plant cells is constantly increasing, especially in the case of valuable woody plants elite varieties where CRISPR-Cas9 technology would preserve their genotype, while still resulting into targeted genetic modifications. The use of single cells fits well the requirements of New Breeding Technologies, by ensuring both the CRISPR-Cas DNA-free delivery as RNPs and, since every plant will be regenerated from a single edited cell, the absence of chimerism. However, the use of protoplasts cell culture from woody plants is generally hampered by low editing efficiencies and an unsuccessful regenerative process.

We here describe a successful DNA-free methodology to obtain fully edited grapevine plants, regenerated from protoplasts obtained from V. vinifera cv. Crimson seedless L. embryogenic callus. The transfected protoplasts were edited on the Downy Mildew susceptibility gene VvDMR6-2. The regenerated edited plants exhibited homozygous deletions of 1bp or 2bp, and homozygous insertion of 1bp.
A new pipeline for the normalization and pooling of metabolomics data
Authors: Viallon Vivian , His Mathilde , Rinaldi Sabina , Breeur Marie , Gicquiau Audrey , Hemon Bertrand , Overvad Kim , Tjønneland Anne , Rostgaard-Hansen Agnetha Linn , Rothwell Joseph A. , Lecuyer Lucie , Severi Gianluca , Kaaks Rudolf , Johnson Theron , Schulze Matthias B. , Palli Domenico , Agnoli Claudia , Panico Salvatore , Tumino Rosario , Ricceri Fulvio , Verschuren Monique , Engelfriet Peter , Onland Charlotte , Vermeulen Roel , Nøst Therese Haugdahl , Urbarova Ilona , Zamora-Ros Raul , Rodriguez-Barranco Miguel , Amiano Pilar , Huerta José Maria , Ardanaz Eva , Melander Olle , Ottoson Filip , Vidman Linda , Rentoft Matilda , Schmidt Julie A , Travis Ruth C , Weiderpass Elisabete , Johansson Mattias , Dossus Laure , Jenab Mazda , Gunter Marc J , Bermejo Lorenzo , Scherer Dominique , Salek Reza M , Keski-Rahkonen Pekka , Ferrari Pietro
Published: July 2021

Pooling metabolomics data across studies is often desirable to increase the statistical power of the analysis. However, this can raise methodological challenges as several preanalytical and analytical factors could introduce differences in measured concentrations and variability between datasets. Specifically, different studies may use variable sample types (e.g., serum versus plasma) collected, treated and stored according to different protocols, and assayed in different laboratories using different instruments. To address these issues, a new pipeline was developed to normalize and pool metabolomics data through a set of sequential steps: (i) exclusions of the least informative observations and metabolites and removal of outliers; imputation of missing data; (ii) identification of the main sources of variability through PC-PR2 analysis; (iii) application of linear mixed models to remove unwanted variability, including samples’ originating study and batch, and preserve biological variations while accounting for potential differences in the residual variances across studies. This pipeline was applied to targeted metabolomics data acquired using Biocrates AbsoluteIDQ kits in eight case-control studies nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Comprehensive examination of metabolomics measurements indicated that the pipeline improved the comparability of data across the studies. Our pipeline can be adapted to normalize other molecular data, including biomarkers as well as proteomics data, and could be used for pooling molecular datasets, for example in international consortia, to limit biases introduced by inter-study variability. This versatility of the pipeline makes our work of potential interest to molecular epidemiologists.
Tensin3 interaction with talin drives formation of fibronectin-associated fibrillar adhesions
Authors: Atherton Paul , Konstantinou Rafaella , Neo Suat Peng , Wang Emily , Balloi Eleonora , Ptushkina Marina , Bennett Hayley , Clark Kath , Gunaratne Jayantha , Critchley David , Barsukov Igor , Manser Edward , Ballestrem Christoph
Published: July 2021

The formation of healthy tissue involves continuous remodelling of the extracellular matrix (ECM). Whilst it is known that this requires integrin-associated cell-ECM adhesion sites (CMAs) and actomyosin-mediated forces, the underlying mechanisms remain unclear. Here we examine how tensin3 contributes to formation of fibrillar adhesions (FBs) and fibronectin fibrillo-genesis. Using BioID mass spectrometry and a mitochondrial targeting assay, we establish that tensin3 associates with the mechanosensors talin and vinculin. We show that the talin R11 rod domain binds directly to a helical motif within the central intrinsically disordered region (IDR) of tensin3, whilst vinculin binds indirectly to tensin3 via talin. Using CRISPR knock-out cells in combination with defined tensin3 mutations, we show (i) that tensin3 is critical for formation of α5β1-integrin FBs and for fibronectin fibrillogenesis, and (ii) the talin/tensin3 interaction drives this process, with vinculin acting to potentiate it.
The HDL particle composition determines its anti-tumor activity in pancreatic cancer
Authors: Bauer Raimund , Kührer Kristina , Udonta Florian , Wroblewski Mark , Ben-Batalla Isabel , Hassl Ingrid , Körbelin Jakob , Röhrl Clemens , Unseld Matthias , Jauhiainen Matti , Hengstschläger Markus , Loges Sonja , Stangl Herbert
Published: July 2021

Despite significant efforts in the last years to improve therapeutic options, pancreatic cancer remains a fatal disease and is expected to become the second leading cause of cancer-related deaths in the next decade. Late diagnosis and a complex, fibrotic tumor microenvironment produces a therapeutically hardly approachable situation with rapidly emerging resistance mechanisms. In response to this hostile microenvironment, previous research identified lipid metabolic pathways to be highly enriched in pancreatic ductal adenocarcinoma (PDAC) cells. Thereby, cholesterol uptake and synthesis was shown to promote a growth advantage to, and chemotherapy resistance for PDAC tumor cells. Here, we demonstrate that efficient, net-cholesterol removal from cancer cells, driven by high-density lipoprotein (HDL) mediated efflux, results in a significant PDAC cell growth reduction, apoptosis and a decreased PDAC tumor development in vivo. This effect is driven by an HDL particle composition-dependent interaction with SR-B1 and ABCA1 on cancer cells, two major lipid flux receptors, which differentially regulate cholesterol transport at the plasma membrane. Eventually, we show that pancreatic cancer patients display reduced plasma levels of HDL-cholesterol, directly translating into a reduced cholesterol efflux capacity of patient-derived plasma samples. We conclude that cholesterol depletion from PDAC cells, together with possible interventions that shunt the import and endogenous synthesis pathways of cholesterol, might represent a promising strategy to increase and complement the currently available treatment options to improve the prognosis of patients suffering from PDAC.
From computing transition probabilities to word recognition in sleeping neonates, a two-step neural tale
Authors: Fló Ana , Benjamin Lucas , Palu Marie , Dehaene-Lambertz Ghislaine
Published: July 2021

Extracting statistical regularities from the environment is a primary learning mechanism, which might support language acquisition. While it is known that infants are sensitive to transition probabilities between syllables in continuous speech, the format of the encoded representation remains unknown. Here we used electrophysiology to investigate how 31 full-term neonates process an artificial language build by the random concatenation of four pseudo-words and which information they retain. We used neural entrainment as a marker of the regularities the brain is tracking in the stream during learning. Then, we compared the evoked-related potentials (ERP) to different triplets to further explore the format of the information kept in memory. After only two minutes of familiarization with the artificial language, we observed significant neural entrainment at the word rate over left temporal electrodes compared to a random stream, demonstrating that sleeping neonates automatically and rapidly extracted the word pattern. ERPs significantly differed between triplets starting or not with the correct first syllable in the test phase, but no difference was associated with later violations in transition probabilities, revealing a change in the representation format between segmentation and memory processes. If the transition probabilities were used to segment the stream, the retained representation relied on syllables’ ordinal position, but still without a complete representation of the words at this age. Our results revealed a two-step learning strategy, probably involving different brain regions.
Huntington’s disease age at motor onset is modified by the tandem hexamer repeat in TCERG1
Authors: Lobanov Sergey V. , McAllister Branduff , McDade-Kumar Mia , Landwehrmeyer G. Bernhard , Orth Michael , Rosser Anne E. ,   for the REGISTRY Investigators of the European Huntington’s disease network, Paulsen Jane S. ,   for the Predict-HD study, Lee Jong-Min , MacDonald Marcy E. , Gusella James F. , Long Jeffrey D. , Ryten Mina , Williams Nigel , Holmans Peter , Massey Thomas H. , Jones Lesley
Published: July 2021

Background

Huntington’s disease is caused by an expanded CAG tract in HTT. The length of the CAG tract accounts for over half the variance in age at onset of disease, and is influenced by other genetic factors, mostly implicating the DNA maintenance machinery. We examined a single nucleotide variant, rs79727797, on chromosome 5 in the TCERG1 gene, previously reported to be associated with Huntington’s disease and a quasi-tandem repeat (QTR) hexamer in exon 4 of TCERG1 with a central pure repeat.

Methods

We developed a novel method for calling perfect and imperfect repeats from exome sequencing data, and tested association between the QTR in TCERG1 and residual age at motor onset (after correcting for the effects of CAG length in the HTT gene) in 610 individuals with Huntington’s disease via regression analysis.

Results

We found a significant association between age at onset and the sum of the repeat lengths from both alleles of the QTR (p = 2.1×10−9), with each added repeat hexamer reducing age at onset by one year (95% confidence interval [0.7, 1.4]). This association explained that previously observed with rs79727797.

Conclusions

The association with age at onset in the genome-wide association study is due to a QTR hexamer in TCERG1, translated to a glutamine/alanine tract in the protein. We could not distinguish whether this was due to cis-effects of the hexamer repeat on gene expression or of the encoded glutamine/alanine tract in the protein. These results motivate further study of the mechanisms by which TCERG1 modifies onset of HD.