bluuebunny/crossref_metadata_2025 huggingface dataset:
A Single-Tube Colorimetric Loop-Mediated Isothermal Amplification for Rapid Detection of SARS-CoV-2 RNA
Authors: Hongjaisee Sayamon , Kham-Kjing Nang , Musikul Piyagorn , Daengkaokhew Wannaporn , Kongson Nuntita , Guntala Ratchadakorn , Jaiyapan Nitipoom , Kline Enos , Panpradist Nuttada , Ngo-Giang-Huong Nicole , Khamduang Woottichai
Published: August 2023

Since SARS-CoV-2 is a highly transmissible virus, a rapid and accurate diagnostic method is necessary to prevent virus spread. We aimed to develop and evaluate a new rapid colorimetric reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay for SARS-CoV-2 detection in a single closed-tube. Nasopharyngeal and throat swabs collected from at-risk individuals testing for SARS-CoV-2 were used to assess the sensitivity and specificity of a new RT-LAMP assay against a commercial qRT-PCR assay. Total RNA extracts were submitted to the RT-LAMP reaction under optimal conditions and amplified at 65°C for 30 minutes using three sets of specific primers targeting the nucleocapsid gene. The reaction was detected using two different indicator dyes, hydroxynaphthol blue (HNB) and cresol red. A total of 82 samples were used for detection with HNB and 94 samples with cresol red, and results were compared with the qRT-PCR assay. The sensitivity of the RT-LAMP-based HNB assay was 92.1% and the specificity was 93.2%. The sensitivity of the RT-LAMP-based cresol red assay was 80.3%, and the specificity was 97%. This colorimetric feature makes this assay highly accessible, low-cost, and user-friendly, which can be deployed for massive scale-up and rapid diagnosis of SARS-CoV-2 infection, particularly in low-resource settings.
Effect of vaccination certification with mass vaccination and non-pharmaceutical interventions on mitigating COVID-19
Authors: Cao Hu , Cao Longbing
Published: August 2023

As COVID-19 vaccines became abundantly available around the world since the second half of 2021, many countries carried out a vaccination certificate (green pass) policy to encourage vaccination and help reopen their economies. This policy granted certified people more freedom of gathering and movement than unvaccinated individuals. Accordingly, pre-existing non-pharmaceutical interventions (NPIs) were adjusted under the vaccination certificate policy. The vaccination certificate also induced heterogeneous behaviors between unvaccinated and vaccinated groups, which complicates the modeling of COVID-19 transmission. Still, limited work is available in evaluating the impact of the green pass policy on COVID-19 transmission using quantitative methods. To characterize the major changes caused by the green pass policy, a modified susceptible-exposed-infected-removed (SEIR) epidemiological model SEIQRD2is proposed in this paper. By integrating different behavior patterns of unvaccinated and vaccinated groups under the green pass policy, SEIQRD2adopts the inherent variability and complexity of human behaviors in the context of vaccination and NPIs and their effect on COVID-19 transmissions. Three countries: Greece, Austria, and Israel are selected as case studies to demonstrate the validity of SEIQRD2. The simulation results illustrate that the combination of NPIs and vaccination still plays a pivotal role in containing the resurgence of COVID-19 by enforcing vaccination certification.
Development and Validation of an Evidence-based Home Pursed Lip Breathing Protocol for Improving Health Outcomes in Patients with COPD
Authors: Huang Houqiang , Da Jun , Watson Roger , Hayter Mark , Huang Min
Published: August 2023

Aim

To develop and validate an evidence-based home PLB intervention protocol for improving related health outcomes (e.g. dyspnea, exercise capability, etc.) in COPD patients and to present a detailed intervention development process.

Methods

Phase one of the Medical Research Council Framework for Developing and Evaluating Complex Interventions was employed to guide the development process of the PLB intervention. The appropriateness of the PLB protocol was finally determined by a panel of experts using the content validity index.

Results

The preliminary PLB intervention protocol was developed based on several underlying rationales, which encompass the extension of expiration time, enhancement of respiratory muscle strength, augmentation of tidal volume, and integration of the most reliable research evidence obtained from four systematic reviews, six RCTs, five clinical trials, and ten recommendations. The PLB intervention was structured with a designated time ratio of inspiration to expiration, set at 1:2. Additionally, the training parameters of the PLB intervention were established as follows: three sessions per day, each lasting for 10 minutes, over a duration of 8 weeks. The intensity of PLB training was individualized, with the inhalation component adjusted according to each participant’s tolerance level, while emphasizing the exhalation phase to ensure complete expulsion of air from the lungs.

Regarding the content validity of the PLB intervention protocol, it demonstrated excellence, as consensus was achieved among all panel experts. Both the item-level and scale-level Content Validity Indices (CVIs) reached the maximum score of 1.0, indicating a high level of agreement and credibility in the content of the protocol as evaluated by the expert panel.

Conclusion

An optimal evidence-based home PLB protocol has been adapted and developed to manage COPD patients’ health-related outcomes. The protocol is transparent and fully supported by relevant mechanisms, concrete evidence, recommendations, and experts’ consensus.

Impact

The development of the PLB intervention protocol has shown considerable variation among studies, resulting in inconclusive effects in COPD patients. Moreover, there is currently a dearth of an evidence-based PLB intervention protocol, particularly in the home setting. Consequently, this study, guided by the MRC framework, has successfully formulated an evidence-based home PLB intervention aimed at enhancing the health outcomes of COPD patients
Plasma water T2detects age-stratified differences in cardiometabolic health among familial CCM patients with Hispanic CCM1 mutation
Authors: Croft Jacob , Sandoval Diana F. , Cistola David , Zhang Jun
Published: August 2023

Introduction

Cerebral cavernous malformations (CCMs) are abnormal clusters of capillaries in the nervous system. This pilot study analyzed the cardiometabolic health status of individuals with familial CCMs caused by a rare mutation in theCCM1gene (fCCM1). The aim was to compare plasma water T2values from individuals with fCCM1 with values from metabolically unhealthy and healthy individuals with no known CCM mutations.

Design

This observational, cross-sectional study included 75 participants: 11 fCCM1 patients, 24 metabolically unhealthy and 40 metabolically healthy individuals. Plasma water T2, an early, global and practical marker of cardiometabolic health, was measured in the time domain using benchtop magnetic resonance relaxometry. The results were stratified by age (≤ 45 vs. >45 years). Group means were compared using Welch’s one-way ANOVA andpost hocTukey-Kramer tests. Multivariable linear regression, with T2as the outcome variable, was used to explore associations with age, gender, Hispanic ethnicity and fCCM1 status.

Results

In the younger age stratum, the fCCM1 group had a mean plasma water T2value comparable to the metabolically healthy group (p=0.6388), but higher than the unhealthy group (p<0.0001). By contrast, in the older stratum, the mean plasma water T2value for the fCCM1 group was comparable to the metabolicallyunhealthy group (p=0.7819) and lower than the healthy group (p=0.0005). Multivariable linear regression revealed that age and theinteractionbetween age and fCCM1 status were significant predictors of T2, even after adjusting for gender and Hispanic ethnicity.

Conclusion

Plasma water T2shows potential as a biomarker for assessing the health status of individuals with fCCM1. Further research is needed to validate these preliminary observations and elucidate the association between CCMs and cardiometabolic health.
Predicting subnational incidence of COVID-19 cases and deaths in EU countries
Authors: Robert Alexis , Chapman Lloyd AC , Grah Rok , Niehus Rene , Sandmann Frank , Prasse Bastian , Funk Sebastian , Kucharski Adam J
Published: August 2023

Background

Recurring COVID-19 waves highlight the need for tools able to quantify transmission risk, and identify geographical areas at risk of outbreaks. Local outbreak risk depends on complex immunity patterns resulting from previous infections, vaccination, waning and immune escape, alongside other factors (population density, social contact patterns). Immunity patterns are spatially and demographically heterogeneous, and are challenging to capture in country-level forecast models.

Methods

We used a spatiotemporal regression model to forecast subnational case and death counts and applied it to three EU countries as test cases: France, Czechia, and Italy. Cases in local regions arise from importations or local transmission. Our model produces age-stratified forecasts given age-stratified data, and links reported case counts to routinely collected covariates (test number, vaccine coverage..). We assessed the predictive performance of our model up to four weeks ahead using proper scoring rules and compared it to the European COVID-19 Forecast Hub ensemble model. Using simulations, we evaluated the impact of variations in transmission on the forecasts. We developed an open-source RShiny App to visualise the forecasts and scenarios.

Results

At a national level, the median relative difference between our median weekly case forecasts and the data up to four weeks ahead was 25% (IQR: 12-50%) over the prediction period. The accuracy decreased as the forecast horizon increased (on average 24% increase in the median ranked probability score per added week), while the accuracy of death forecasts remained stable. Beyond two weeks, the model generated a narrow range of likely transmission dynamics. The median national case forecasts showed similar accuracy to forecasts from the European COVID-19 Forecast Hub ensemble model, but the prediction interval was narrower in our model. Generating forecasts under alternative transmission scenarios was therefore key to capturing the range of possible short-term transmission dynamics.

Discussion

Our model captures changes in local COVID-19 outbreak dynamics, and enables quantification of short-term transmission risk at a subnational level. The outputs of the model improve our ability to identify areas where outbreaks are most likely, and are available to a wide range of public health professionals through the Shiny App we developed.
Digital Mental Health Service engagement changes during Covid-19 in children and young people across the UK: presenting concerns, service activity, and access by gender, ethnicity, and deprivation
Authors: Knipe Duleeka , de Ossorno Garcia Santiago , Salhi Louisa , Mainstone-Cotton Lily , Sefi Aaron , John Ann
Published: August 2023

The adoption of digital health technologies accelerated during Covid-19, with concerns over the equity of access due to digital exclusion. Using data from a text-based online mental health service for children and young people we explore the impact of the pandemic on service access and presenting concerns and whether differences were observed by sociodemographic characteristics in terms of access (gender, ethnicity and deprivation). We used interrupted time-series models to assess whether there was a change in the level and rate of service use during the Covid-19 pandemic (April 2020-April 2021) compared to pre-pandemic trends (June 2019-March 2020). Routinely collected data from 61221 service users were extracted for observation, those represented half of the service population as only those with consent to share their data were used. The majority of users identified as female (74%) and White (80%), with an age range between 13 and 20 years of age,. There was evidence of a sudden increase (13%) in service access at the start of the pandemic (RR 1.13 95% CI 1.02, 1.25), followed by a reduced rate (from 25% to 21%) of engagement during the pandemic compared to pre-pandemic trends (RR 0.97 95% CI 0.95,0.98). There was a sudden increase in almost all presenting issues apart from physical complaints. There was evidence of a step increase in the number of contacts for Black/African/Caribbean/Black British (38% increase; 95% CI: 1%-90%) and White ethnic groups (14% increase; 95% CI: 2%-27%)), sudden increase in service use at the start of the pandemic for the most (58% increase; 95% CI: 1%-247%) and least (47% increase; 95% CI: 6%-204%) deprived areas. During the pandemic, contact rates decreased, and referral sources change at the start. Findings on access and service activity align with other studies observing reduced service utilization. The lack of differences in deprivation levels and ethnicity at lockdown suggests exploring equity of access to the anonymous service. The study provides unique insights into changes in digital mental health use during Covid-19 in the UK.
Determinants of gender disparities in psychological distress among youth and adults in South Africa: Evidence from the 2017 national population-based household survey
Authors: Zungu Nompumelelo P. , Makusha Tawanda , Makola Lehlogonolo , Mabaso Musawenkosi , Shisana Olive
Published: August 2023

Background

Psychological distress has become a significant public health concern, and gender differences in psychological distress are well documented in the literature. This study investigated determinants of gender disparities in psychological distress among youth and adults in South Africa.

Methods

This study data used obtained from the 2017 National HIV Prevalence, Incidence, Behaviour, and Communication Survey conducted using a multi-stage stratified random cluster sampling design. Multivariate backward stepwise logistic regression models were used to determine the factors associated with psychological distress among males and females.

Results

In the male model, the odds of psychological distress were significantly higher among those who reported fair/poor self-rated health [AOR=1.7% (95% CI: 1.2-2.4), p=0.003], and excessive alcohol users [AOR=1.6% (95% CI: 1.1-2.3), p=0.008]. The odds were significantly lower among those with tertiary education level [AOR=0.5% (95% CI: 0.3-0.9), p=0.031], those from rural formal/farm areas [AOR=0.6% (95% 0.4-1.0), p=0.046], and those who were HIV negative [AOR=0.7% (95% CI: 0.4-1.0), p=0.051]. In the female model, the odds of psychological distress were significantly higher among those who reported fair/poor self-rated health [AOR=2.6% (95% CI: 2.0-3.4), p<0.001], and excessive alcohol users [AOR=2.0% (95% CI: 1.3-3.1), p=0.002]. The odds were significantly lower among the employed [AOR=0.7% (95% CI: 0.5-0.9), p=0.002], those from rural informal/tribal areas [AOR=0.6% (95% CI: 0.5-0.8), p=0.001], rural formal/farm areas [AOR=0.6% (95% CI: 0.4-0.9), p=0.015], and those with correct HIV knowledge and myth rejection [AOR=0.6% (95% CI: 0.4-0.7), p<0.001].

Conclusion

The findings highlight the need for tailored gender-specific interventions and targeting identified high-risk groups. The finding also underscores the importance of integrated interventions to address the adverse effects of harmful alcohol use and HIV-positive serostatus on psychological distress.
The CAPP 2 Study Protocol: Strengthening the capacity of healthcare providers to reduce the impact of COVID-19 on African, Caribbean, and Black communities in Ontario
Authors: Etowa Josephine , Loemba Hugues , Bailey Liana , Yaya Sanni , Dabone Charles , Etowa Egbe B. , Ghose Bishwajit , Ajiboye Wale , Tyerman Jane , Luctkar-Flude Marian , Rayner Jennifer , Nnorom Onyenyechukwu , Taylor Robin , Beauchamp Sheryl , Oneka Goldameir , Kohoun Bagnini , Tharao Wangari , Inoua Haoua , Edet Ruby , Kiirya Joseph , Allibhai Soraya , Kirunga Ky’okusinga , Kemei Janet
Published: August 2023

Introduction

The COVID-19 pandemic emerged as an unprecedented challenge for healthcare systems across the world disproportionately impacting immigrant and racialized populations. Canadian African, Caribbean, and Black (ACB) communities representing some of the most vulnerable populations in terms of their susceptibility to health risks, receipt of adequate care, and chances of recovery. The COVID-19 ACB Providers Project (CAPP 2) aims to strengthen the ability of health care providers (HCP) to address this community’s COVID-19 related healthcare needs. Informed by CAPP 1.0 Project, a mixed-method study which examined COVID-19 pandemic impact on ACB communities in Ontario (Ottawa and Toronto), this second study seeks to develop and implement educational programs on five key areas (modules) to strengthen the capacity of HCPs working with ACB populations. The five modules (topics) include: 1) COVID-19 and its impacts on health, 2) social determinants of health and health inequities, 3) critical health literacy, 4) critical racial literacy, and 5) cultural competence and safety.

Methods and analysis

An implementation science approach will guide the development, implementation, and evaluation of the evidence-informed interventions. Intersectionality lens, socio-ecological model (SEM) and community-based participatory research (CBPR) frameworks will inform the research process. To ensure active stakeholder engagement, there will be a Project Advisory Committee comprised of 16 ACB community members, health providers, and partner agency representatives. Five modules will be developed: two virtual simulation games in collaboration with leading simulation experts, and three non-simulation modules.

Ethics and dissemination

Ethics approval was granted by the University of Ottawa Research Ethics Board on July 18th, 2023 (H - 01-23 - 8069). The results of this study will be disseminated in community workshops, an online learning platform, at academic conferences and in peer-reviewed publications.
No change in 24-hour salt intake estimated from spot urine in Norwegian adults from 2006 to 2019. The population-based HUNT Study
Authors: Holvik Kristin , Abel Marianne Hope , Holmen Jostein , Krokstad Steinar , Totland Torunn Holm , Meyer Haakon E
Published: August 2023

Objective

Monitoring time trends in salt consumption is important for evaluating the impact of salt reduction initiatives on public health outcomes. There has so far not been available data to indicate if salt consumption in Norway has changed during the previous decade. We aimed to assess whether average 24-hour salt intake estimated from spot urine samples in the adult population of mid-Norway changed from 2006-08 to 2017-19, and to describe variations by sex, age, and educational level.

Design

Repeated cross-sectional studies.

Setting

The population-based HUNT Study.

Participants

In each of two consecutive waves (HUNT3: 2006-08 and HUNT4: 2017-19), spot urine samples were collected from 500 men and women aged 25-64 years, in addition to 250 men and women aged 70-79 years in HUNT4. Based on spot urine concentrations of sodium, potassium and creatinine, age, sex, and body mass index, we estimated 24-hour sodium intake using the INTERSALT equation for the Northern European region.

Results

Mean (95% confidence interval (CI)) estimated 24-hour salt intakes in men were 11.1 (95% CI 10.8, 11.3) g in HUNT3 and 10.9 (95% CI 10.6, 11.1) g in HUNT4, p=0.25.

Corresponding values in women were 7.7 (95% CI 7.5, 7.9) g and 7.7 (95% CI 7.5, 7.9) g, p=0.88. Mean estimated salt intake in HUNT4 decreased with increasing age in women, but not in men, and it did not differ significantly across educational level in either sex.

Conclusions

Estimated 24-hour salt intake in adult men and women in mid-Norway did not change from 2006-08 to 2017-19.
Safely managed sanitation practice and childhood stunting among under five years old children in Myanmar
Authors: Soe Than Kyaw , Laohasiriwong Wongsa , Sornlorm Kittipong , Mahato Roshan Kumar
Published: August 2023

In 2020, 149 million children under the age of five were estimated to be stunted globally. Around half of deaths among children under 5 years of age are related to under-nutrition. Objective of this study is to determine the association between safely managed sanitation and childhood stunting among under-five years old children in Myanmar. This cross-sectional analytical study was conducted in 16 townships across three regions and five states in Myanmar. Multiple logistic regressions analysis was performed to determine the associations. This study found that 327 (27.09%) under-five children were stunted among a total of 1207 children in Myanmar. Children with unsafely managed sanitation were 2.88 times more likely to be stunting compared with children who access to safely managed sanitation services (AOR=2.88, 95% CI: 2.16 to 3.85; p-value <0.01). Other associated factors for childhood stunting were needs 1-15 minutes for water collection (AOR=2.07, 95% CI: 1.46 to 2.94; p-value <0.01), 15-60 minutes for water collection times (AOR=1.55, 95% CI: 1.08 to 2.23; p-value 0.02), unproper waste water disposal (AOR=1.99, 95% CI: 1.47 to 2.70; p-value <0.01), boys children (AOR=4.49, 95% CI: 3.30 to 6.12; p-value <0.01), did not take vitamin A supplements(AOR=1.64, 95% CI: 1.22 to 2.20; p-value <0.01), mothers height shorter than 153.4cm (AOR=1.94, 95% CI: 1.45 to 2.58; p-value <0.01), and the lower minimal diet diversity (AOR=1.53, 95% CI: 1.11 to 1.87; p-value 0.02). More access to safely managed sanitation facilities, technical sharing for proper waste water disposal, promoting household water supply system, health promotion for children’s diet eating pattern, and regular support for Vitamin A supplementation are critical to reduce childhood stunting among children under the age of five in Myanmar.
Dispensaries and medical marijuana certifications and indications: Unveiling the geographic connections in Pennsylvania, USA
Authors: Hirsch Annemarie G. , Wright Eric A. , Nordberg Cara M. , DeWalle Joseph , Stains Elana L. , Kennalley Amy L. , Zhang Joy , Tusing Lorraine D. , Piper Brian J.
Published: August 2023

Background

Pennsylvania opened its first medical marijuana (MMJ) dispensary in 2018. Qualifying conditions include six conditions determined to have insufficient evidence to support or refute MMJ effectiveness. We conducted a study to describe MMJ dispensary access in Pennsylvania and to determine whether dispensary proximity was associated with MMJ certifications and community demographics.

Methods

Using data from the Pennsylvania Department of Health, we geocoded MMJ dispensary locations and linked them to U.S. Census Bureau data. We created dispensary access measures from the population-weighted centroid of Zip Code Tabulation Areas (ZCTAs): distance to nearest dispensary and density of dispensaries within a 15-minute drive.

We evaluated associations between dispensary access and the proportion of adults who received MMJ certification and the proportion of certifications for insufficient evidence conditions (amyotrophic lateral sclerosis, epilepsy, glaucoma, Huntington’s disease, opioid use disorder, and Parkinson’s disease) using negative binomial modeling, adjusting for community features. To evaluate associations between the proportion of the population that was non-White, Hispanic, or both (NW-H) and distance to nearest dispensary, we used logistic regression to estimate the odds ratios (OR) and 95% confidence intervals (CI), adjusting for median income.

Results

Distance and density of MMJ dispensaries was associated with the proportion of the ZCTA population certified and the proportion of certifications for limited evidence conditions. Compared to ZCTAs with no dispensary within 15 minutes, the proportion of adults certified increased by up to 31% and the proportion of certifications for limited evidence decreased by up to 22% for ZCTAs with two dispensaries. In 2021, the odds of being within five miles of a dispensary was higher in ZCTAs with the highest proportions of NW-H individuals (OR: 26.05, CI: 16.7 - 40.6), compared to ZCTAs with the lowest proportions.

Conclusions

Greater dispensary access was associated with the proportions of certified residents and certifications for insufficient evidence conditions. Whether these patterns are due to differences in accessibility or demand is unknown. Associations between community demographics and dispensary proximity may indicate MMJ access differences.
Integrated spatial transcriptomics and lipidomics of precursor lesions of pancreatic cancer identifies enrichment of long chain sulfatide biosynthesis as an early metabolic alteration
Authors: Sans Marta , Chen Yihui , Thege Fredrik I. , Dou Rongzhang , Min Jimin , Yip-Schneider Michele , Zhang Jianjun , Wu Ranran , Irajizad Ehsan , Makino Yuki , Rajapakshe Kimal I. , Hurd Mark W. , León-Letelier Ricardo A. , Vykoukal Jody , Dennison Jennifer B. , Do Kim-Anh , Wolff Robert A. , Guerrero Paola A. , Kim Michael P. , Schmidt C Max , Maitra Anirban , Hanash Samir , Fahrmann Johannes F.
Published: August 2023

Background

The development of diverse spatial profiling technologies has provided an unprecedented insight into molecular mechanisms driving cancer pathogenesis. Here, we conducted the first integrated cross-species assessment of spatial transcriptomics and spatial metabolomics alterations associated with progression of intraductal papillary mucinous neoplasms (IPMN),bona fidecystic precursors of pancreatic ductal adenocarcinoma (PDAC).

Methods

Matrix Assisted Laster Desorption/Ionization (MALDI) mass spectrometry (MS)-based spatial imaging and Visium spatial transcriptomics (ST) (10X Genomics) was performed on human resected IPMN tissues (N= 23) as well as pancreata from a mutantKras;Gnasmouse model of IPMN. Findings were further compared with lipidomic analyses of cystic fluid from 89 patients with histologically confirmed IPMNs, as well as single-cell and bulk transcriptomic data of PDAC and normal tissues.

Results

MALDI-MS analyses of IPMN tissues revealed long-chain hydroxylated sulfatides, particularly the C24:0(OH) and C24:1(OH) species, to be selectively enriched in the IPMN and PDAC neoplastic epithelium. Integrated ST analyses confirmed that the cognate transcripts engaged in sulfatide biosynthesis, includingUGT8, Gal3St1, andFA2H, were co-localized with areas of sulfatide enrichment. Lipidomic analyses of cystic fluid identified several sulfatide species, including the C24:0(OH) and C24:1(OH) species, to be significantly elevated in patients with IPMN/PDAC compared to those with low-grade IPMN. Targeting of sulfatide metabolism via the selective galactosylceramide synthase inhibitor, UGT8-IN-1, resulted in ceramide-induced lethal mitophagy and subsequent cancer cell deathin vitro, and attenuated tumor growth of mutantKras;Gnasallografts. Transcript levels ofUGT8andFA2Hwere also selectively enriched in PDAC transcriptomic datasets compared to non-cancerous areas, and elevated tumoralUGT8was prognostic for poor overall survival.

Conclusion

Enhanced sulfatide metabolism is an early metabolic alteration in cystic pre-cancerous lesions of the pancreas that persists through invasive neoplasia. Targeting sulfatide biosynthesis might represent an actionable vulnerability for cancer interception.
SARS-CoV-2 infection triggers pro-atherogenic inflammatory responses in human coronary vessels
Authors: Eberhardt Natalia , Noval Maria Gabriela , Kaur Ravneet , Sajja Swathy , Amadori Letizia , Das Dayasagar , Cilhoroz Burak , Stewart O’Jay , Fernandez Dawn M. , Shamailova Roza , Guillen Andrea Vasquez , Jangra Sonia , Schotsaert Michael , Gildea Michael , Newman Jonathan D. , Faries Peter , Maldonado Thomas , Rockman Caron , Rapkiewicz Amy , Stapleford Kenneth A. , Narula Navneet , Moore Kathryn J. , Giannarelli Chiara
Published: August 2023

COVID-19 patients present higher risk for myocardial infarction (MI), acute coronary syndrome, and stroke for up to 1 year after SARS-CoV-2 infection. While the systemic inflammatory response to SARS-CoV-2 infection likely contributes to this increased cardiovascular risk, whether SARS-CoV-2 directly infects the coronary vasculature and attendant atherosclerotic plaques to locally promote inflammation remains unknown. Here, we report that SARS-CoV-2 viral RNA (vRNA) is detectable and replicates in coronary atherosclerotic lesions taken at autopsy from patients with severe COVID-19. SARS-CoV-2 localizes to plaque macrophages and shows a stronger tropism for arterial lesions compared to corresponding perivascular fat, correlating with the degree of macrophage infiltration.In vitroinfection of human primary macrophages highlights that SARS-CoV-2 entry is increased in cholesterol-loaded macrophages (foam cells) and is dependent, in part, on neuropilin-1 (NRP-1). Furthermore, although viral replication is abortive, SARS-CoV-2 induces a robust inflammatory response that includes interleukins IL-6 and IL-1β, key cytokines known to trigger ischemic cardiovascular events. SARS-CoV-2 infection of human atherosclerotic vascular explants recapitulates the immune response seen in cultured macrophages, including pro-atherogenic cytokine secretion. Collectively, our data establish that SARS-CoV-2 infects macrophages in coronary atherosclerotic lesions, resulting in plaque inflammation that may promote acute CV complications and long-term risk for CV events.
FCS-Like Zinc finger 14 (FLZ14) mediates the crosstalk between TORC and SnRK1 in response to sugar availability
Authors: Artins Anthony , Urrea-Castellanos Reynel , Martin-Sánchez Marcos , Alexandre Moraes Thiago , Fernie Alisdair R. , Satake Akiko , Caldana Camila
Published: August 2023

Matching resource availability to growth is crucial for plant fitness. We identified that FCS- Like Zinc finger 14 (FLZ14) gauges carbon (C) status to adjust growth by inhibiting the TARGET OF RAPAMYCIN (TOR) activity in short days via REGULATORY- ASSOCIATED PROTEIN OF TARGET OF RAPAMYCIN 1B (RAPTOR1B). Besides being transcriptionally induced by sugars, the amplitude ofFLZ14induction correlates to the diel sugar status, indicating thatFLZ14responses to sugar oscillationsin planta.Genetic evidence elucidated that FLZ14 is involved in the crosstalk between TORC and SUCROSE NON-FERMENTING RELATED KINASE 1 (SnRK1). In short photoperiods,FLZ14andKIN10genetically interact to set the pace of TORC activity. By contrast, under long day photoperiods,FLZ14andRAPTOR1Bgenetically interact, most likely to downregulate SnRK1 signalling. This report highlights the function of a sugar-responsive gene in mediating the crosstalk between TORC and SnRK1 to fine-tune growth.
The longitudinal single-cell panorama of cynomolgus monkey ovary throughout lifespan revealed a conserved ovarian clock between primates
Authors: Yan Long , Long Xin , Zhao Yan , Zhao FeiYan , Tu Wan , Yang Qiuyun , Qian Jingjing , Zhai Jinglei , Wang Meijiao , Hu Yuqiong , He Beijia , Su Youqiang , Jiang Xiangxiang , Gao Fei , Wang Hongmei , Guo Fan
Published: August 2023

Ovarian function is critical for female fertility and impacts reproductive longevity. It is of great importance to accurately predict the aging process within the ovary for fertility assessment and disease diagnosis. However, cell metrics for evaluating the ovarian aging rate are still in urgent need, and molecular insights into ovarian development and dysfunction during the primate life course are also limited. Here, we reported large-scale ovarian cell atlas of consecutive development of cynomolgus monkeys across 22 years with 20 time points, covering the foetal, newborn, prepubertal, pubertal, adult, perimenopausal and menopausal stages. We characterized and validated distinct molecular signatures of each cluster of cells within primate ovaries, and uncovered a previously undocumented RHOXF1-positive oocyte type during primordial follicle assembly in primates. Furthermore, the constitution and developmental trajectories of primate germ cells, granulosa cells and stromal / theca cells were also elucidated, and their precursors were identified. More importantly, dynamics of cellular compositions were unravelled through the ovarian development, featured by granulosa, epithelial, stromal, and immune cells that showed strong temporal heterogeneity spanning lifetime, whilst referred to the key function during the corresponding stages. Based on the correlations of each cell type with age and stage-specific molecular dynamics, we further constructed a transcriptomic ovarian clock which could perceive an effective biological age prediction of the ovary and further applied to humans. The findings reveal granulosa, epithelial, and stromal cells as the highest performance predictors of ovarian biological age, while highlighting the crucial role of AGE-RAGE and Relaxin signaling pathways in regulating ovarian aging. Our work not only provide valuable resource for obtaining insights into the development, aging and dysfunction of key organs, but also establish a transcriptomic clock to predict biological ovarian aging thus to be potential clinical implementation in future.
Enhancing CRISPR prime editing by reducing misfolded pegRNA interactions
Authors: Zhang Weiting , Petri Karl , Ma Junyan , Lee Hyunho , Tsai Chia-Lun , Joung J. Keith , Yeh Jing-Ruey Joanna
Published: August 2023

CRISPR prime editing (PE) requires a Cas9 nickase-reverse transcriptase fusion protein (known as PE2) and a prime editing guide RNA (pegRNA), an extended version of a standard guide RNA (gRNA) that both specifies the intended target genomic sequence and encodes the desired genetic edit. Here we show that sequence complementarity between the 5’ and the 3’ regions of a pegRNA can negatively impact its ability to complex with Cas9, thereby potentially reducing PE efficiency. We demonstrate this limitation can be overcome by a simple pegRNA refolding procedure, which improved ribonucleoprotein-mediated PE efficiencies in zebrafish embryos by up to nearly 25-fold. Further gains in PE efficiencies of as much as 6-fold could also be achieved by introducing point mutations designed to disrupt internal interactions within the pegRNA. Our work defines simple strategies that can be implemented to improve the efficiency of PE.
Integrative phenotypic-transcriptomic analysis of soybean plants subjected to multifactorial stress combination
Authors: Peláez-Vico María Ángeles , Sinha Ranjita , Induri Sai Preethi , Lyu Zhen , Venigalla Sai Darahas , Vasireddy Dinesh , Singh Pallav , Immadi Manish Sridhar , Pascual Lidia S. , Shostak Benjamin , Mendoza-Cózatl David , Joshi Trupti , Fritschi Felix B. , Zandalinas Sara I. , Mittler Ron
Published: August 2023

Global warming, climate change, and industrial pollution are altering our environment subjecting crops to an increasing number and complexity of abiotic stress conditions, concurrently or sequentially. Recent studies revealed that a combination of 3 or more stresses simultaneously impacting a plant (termed ‘multifactorial stress combination’; MFSC) can cause a drastic decline in plant growth and survival, even if the level of each stress involved in the MFSC has a negligible effect on plants. However, the impacts of MFSC on crops are largely unknown. We subjected soybean plants to a MFSC of up to five different stresses (water deficit, salinity, low phosphate, acidity, and cadmium), in an increasing level of complexity, and conducted integrative transcriptomic-phenotypic analysis of reproductive and vegetative tissues. We reveal that MFSC has a negative cumulative effect on soybean yield, that each set of MFSC condition elicits a unique transcriptomic response (that is different between flowers and leaves), and that selected genes expressed in leaves or flowers are linked to the effects of MFSC on different vegetative, physiological, and/or reproductive parameters. We further reveal that the transcriptomic response of soybean andArabidopsisto MFSC shares common features associated with reactive oxygen and iron/copper signaling/metabolism. Our study provides unique phenotypic and transcriptomic datasets for dissecting the mechanistic effects of MFSC on the vegetative, physiological, and reproductive processes of a crop plant.
Cortactin stabilizes actin branches by bridging activated Arp2/3 to its nucleated actin filament
Authors: Liu Tianyang , Cao Luyan , Mladenov Miroslav , Jegou Antoine , Way Michael , Moores Carolyn A.
Published: August 2023

Regulation of the assembly and turnover of branched actin filament networks nucleated by the Arp2/3 complex is essential during many cellular processes including cell migration and membrane trafficking. Cortactin plays a key role in stabilizing actin filament branches by interacting with the Arp2/3 complex and actin filaments via its N-terminal Acidic domain (NtA) and 6.5 central unstructured 37 amino acid repeats, respectively1, but the mechanism of this is unclear. We determined the structure of cortactin-stabilized Arp2/3 actin branches using cryo-electron microscopy. We find that cortactin interacts with the new daughter filament nucleated by the Arp2/3 complex at the branch site rather than the initial mother actin filament. Cortactin preferentially binds activated Arp3 in contrast to other nucleation promoting factors (NPFs)2,3. Cortactin also stabilizes the F-actin-like interface of activated Arp3 with the first actin subunit of the new filament, and its central repeats extend along successive daughter filament subunits. Cortactin binding to Arp3 is incompatible with NPF interaction and its preference for activated Arp3 explains why it is retained at the actin branch. Our data have uncovered why cortactin displaces NPFs, while at the same time promoting synergy to regulate branched actin network dynamics.
Alcohol Responsive Genes in the Neutrophils of Acute-On-Chronic Liver Failure Reveal Modulation of Intracellular Calcium, ROS, and Phagocytosis
Authors: Saha Rohini , Chakraborty Ditam , Roshan Aditya , Sharma Shalini , Loganathan Tamizhini , Shalimar  , Acharya Pragyan
Published: August 2023

Acute-on-chronic liver failure (ACLF) is characterized by rapid depletion of hepatic reserves, innate immunity-driven pathogenesis and high short-term mortality. Elevation of neutrophil counts is associated with mortality in alcoholic-ACLF. In India, one of the most common etiologies in ACLF for both chronic and acute injury is alcohol. We used a combination of clinical transcriptomics and a novelin vitrolaboratory model to look at gene signatures unique in alcoholic ACLF patients and study phenotypic changes upon alcohol treatment. CCL20 and IL1β were two of the top overexpressed genes in alcoholic-ACLF which were validated in the alcohol-neutrophil model, using neutrophils isolated from CLD patients (acute-on-chronic model), and healthy individual (acute model). In the alcoholic-neutrophil models, 300 mg/dL dose of ethanol for 24 hours, caused reduced ROS generation, reduced phagocytic ability and dampening of intracellular calcium reserves. We conclude that the effects of alcohol at least partially explain immune dysfunction in ACLF such as dampening of ROS and phagocytosis in neutrophils while retaining inflammatory roles such as expression of CCL20 and IL1β. Systematic curation of previously published alcohol related liver tissue transcriptomic data also confirmed overlapping genes with alcoholic-ACLF circulating neutrophils. Docking of ethanol with CCL20 and IL1β showed spontaneous binding.
Crystal structure and Hirshfeld surface analysis of 3-(bromomethyl)-2-[1,2-dibromo-2-(6-nitrobenzo[d][1,3]dioxol-5-yl)ethyl]-1-(phenylsulfonyl)-1H-indole chloroform 0.585-solvate
Authors: Achyuta Nagaraj , Kanagasabai Somarathinam , Vinayagam Pavunkumar , Mohanakrishnan Arasambattu K. , Gautham Namasivayam , Gunasekaran Krishnasamy
Published: August 2023

The title indole derivative, C24H17Br3N2O6S, crystallizes with a partial occupancy [0.585 (4)] CHCl3 solvent molecule. The dihedral angles between the indole ring system and pendant nitrobenzodioxolane rings system and phenylsulfonyl ring are 4.81 (14) and 72.24 (19)°, respectively. In the crystal, the indole molecules are linked to each other and to the chloroform molecule by weak C—H...O, C—H...Cl, C—H...π, C—Br...π and C—Cl...π and aromatic π–π stacking interactions. A Hirshfeld surface analysis was carried out and the intermolecular contacts with the most significant contributions are H...O/O...H (24.3%), H...H (18.4%), Br...H/H...Br (16.8%) and C...H/H...C (8.4%).
Construction SMEs labour productivity: causal layered analysis
Authors: Adebowale Oluseyi Julius , Agumba Justus Ngala
Published: August 2023

Purpose

Small and medium-sized contractors are critical to micro and macroeconomic performance. These contractors in South Africa have long been confronted with the problem of business failure because of a plethora of factors, including poor productivity. The purpose of this study is to investigate salient issues undermining the productivity of small and medium-sized contractors in South Africa. This study proposes alternative possibilities to engender productivity improvement.

Design/methodology/approach

Qualitative data were collected using semi-structured interviews with 15 contractors in Gauteng Province, South Africa. The research data were analysed using content and causal layered analyses.

Findings

Challenges to contractors’ productivity were associated with inadequately skilled workers, management competence and political factors. Skills development, construction business and political factors were dominant stakeholders’ perceptions. Metaphors for construction labour productivity are presented and reconstructed as alternative directions for productivity improvement.

Practical implications

Contractors lose a substantial amount of South African Rand to poor productivity. Alternative directions provided in this study can be leveraged to increase profitability in construction organizations, enhance the social well-being of South Africans and ultimately improve the contribution of contractors to the South African economy.

Originality/value

The causal layered analysis (CLA) applied in this study is novel to construction labour productivity research. The four connected layers of CLA, which make a greater depth of inquiry possible, were explored to investigate labour productivity in construction organizations.
Corruption fight in the Czech Republic: sustainability reports evidence
Authors: Kristek Tomas
Published: August 2023

Purpose

The lack of transparency contributes to the growing corruption problem in various spheres of society. This paper aims to analyse the sustainability report disclosures published by Czech companies in 2021 and registered by the Association of Social Sustainability of the Czech Republic.

Design/methodology/approach

Based on three hypotheses, the relationships between the level of disclosed anti-corruption information and selected variables related to the corporate environment are tested using content analysis and the Mann–Whitney test.

Findings

This paper reveals that Czech firms provide more information if they operate in a higher-risk environment (energy, materials and financial services) or are state-owned (or with a state ownership stake). It also reveals that companies participating in corporate social responsibility (CSR) initiatives (UN Global Compact and Global Reporting Initiative) increase their credibility and social responsibility with more disclosed information.

Research limitations/implications

A limitation of this paper is the smaller number of selected companies matching the chosen criteria. In addition, a certain degree of subjectivity is likely to have manifested in the process of coding the reports and in the use of the content analysis method.

Originality/value

The paper contributes to research that addresses the fight against corruption and CSR issues with a specific study in a small, Central European country and provides new empirical data on the anti-corruption fight problem.
Relative informative power and stock return predictability: a new perspective from Egypt
Authors: Hendawy Enas , McMillan David G. , Sakr Zaki M. , Shahwan Tamer Mohamed
Published: August 2023

Purpose

This paper aims to introduce a new perspective on long-term stock return predictability by focusing on the relative (individual and hybrid) informative power of a wide range of accounting (firm-related), technical and macroeconomic factors while considering the past performance of the stocks using machine learning algorithms.

Design/methodology/approach

The sample includes a panel data set of 94 non-financial firms listed in Egyptian Exchange 100 index from 2014: Q1 to 2019: Q4. Relativity has been investigated by comparing relevant factors’ individual and combined informative power and differentiating between losers and winners based on historical stock returns. To predict the quarterly stock returns, Gaussian process regression (GPR) has been used. The robustness of the results is examined through the out-of-sample test. This study also uses linear regression (LR) as a benchmark model.

Findings

The past performance and the presence of other predictors influence the informative power of relevant factors and hence their predictive ability. The out-of-sample results show a trade-off between GPR and LR with proven superiority to GPR in limited experiments. The individual informative power outperforms the hybrid power, in which macroeconomic indicators outperform the remaining sets of indicators for losers, while winners show mixed results in terms of various performance evaluation metrics. Prediction accuracy is generally higher for losers than for winners.

Practical implications

This study provides interesting insight into the dynamic nature of the predictor variables in terms of stock return predictability. Hence, this study also deepens the understanding of asset pricing in a way that directly contributes to practitioners’ portfolio diversification strategies.

Originality/value

In concern of the chaos of factors in the literature and its accompanying misleading conclusions, this study takes another look at the approach that studies stock return predictability. To the best of the authors’ knowledge, this is the first study in the Egyptian context that re-examines the predictive power of the previously discovered factors from a different perspective that highlights their relative nature.
New social media nones: how and why Americans have changed their use of social media to consume political news
Authors: Morris David S. , Morris Jonathan S.
Published: August 2023

Purpose

Social media (SM) platforms have become major sources for generating, sharing and gathering political and election news. Although there appears to be an assumption that reliance on SM for political news consumption will continue to gain in popularity, there are reasons to believe that many Americans are retreating from using SM for political news. The purpose of this study is to examine if Americans are reducing reliance on SM for political news and to analyze why retreat may be happening.

Design/methodology/approach

Using longitudinal panel data from Pew’s American Trends Panel study, the authors tracked 993 respondents from February of 2016 to November of 2019 to monitor their reliance on SM for political news leading up to the 2020 US presidential election.

Findings

The results of this study indicate that a sizeable percentage of people (about a third) are retreating from SM platforms for political news consumption and some are abandoning it altogether – people we refer to as new SM “nones.” The authors find that retreat from SM is associated with increased distrust of the information found on the platforms. Concerns about fake news, incivility on SM and information overload were unrelated to retreat from use of SM for political news consumption.

Originality/value

The findings of this study are novel and suggest that reliance on SM for political news by the public may have waxed, seen its zenith and may now be waning largely because of distrust in the information found on SM platforms.