bluuebunny/crossref_metadata_2025 huggingface dataset:
Coronary Assessment in Heart Failure within a Safety-Net Setting: Disparities and Outcomes
Authors: Durstenfeld Matthew S. , Thakkar Anjali , Ma Yifei , Zier Lucas S. , Davis Jonathan D. , Hsue Priscilla Y.
Published: July 2023

Background

Though ischemic cardiomyopathy is the leading cause of heart failure (HF), most patients do not undergo coronary assessment after heart failure diagnosis. In a safety-net population, referral patterns have not been studied, and it is unknown whether coronary assessment is associated with improved HF outcomes.

Methods

Using an electronic health record cohort of all individuals with HF within San Francisco Health Network from 2001-2019, we identified factors associated with completion of coronary assessment (invasive coronary angiography, nuclear stress, or coronary computed tomographic angiography). Then we emulated a randomized clinical trial of elective coronary assessment with outcomes of all-cause mortality and a composite outcome of mortality and emergent angiography. We used propensity scores to account for differences between groups. We used national death records to improve ascertainment of mortality.

Results

Among 14,829 individuals with HF (median 62 years old, 5,855 [40%] women), 3,987 (26.9%) ever completed coronary assessment, with 2,467 (18.5%) assessed out of 13,301 with unknown CAD status at HF diagnosis. Women and older individuals were less likely to complete coronary assessment, with differences by race/ethnicity, medical history, substance use, housing, and echocardiographic findings. Among 5,972 eligible for inclusion in the “target trial,” 627 underwent early elective coronary assessment and 5,345 did not. Coronary assessment was associated with lower mortality (HR 0.84; 95% CI 0.72-0.97; p=0.025), reduced risk of the composite outcome, higher rates of revascularization, and higher use of medical therapy.

Conclusions

In a safety-net population, disparities in coronary assessment after HF diagnosis are not fully explained by CAD risk factors. Our target trial emulation suggests coronary assessment is associated with improved HF outcomes possibly related to higher rates of revascularization and GDMT use, but with low certainty that this is finding is not attributable to unmeasured confounding.

Abstract Figure

Graphical Abstract:
REDUCING DOOR‐TO‐BALLOON TIME USING EMS INITIATED APP BASED COMMUNICATION
Authors: Abrahim Christian , Capatina Alina , Kalyan‐Sundaram Arvind , Lotfi Amir
Published: July 2023

Background

Reducing door-to-balloon (D2B) time for ST-Segment Elevation Myocardial Infarctions (STEMI) has been shown to be effective in improving outcomes. Delays still occur due to various factors such as time to lab activation and diagnostic clarification in equivocal cases. We propose that early communication through a mobile application between Emergency Medical Services (EMS) and in-hospital providers can reduce EMS-to-balloon time and D2B time.

Methods

We implemented the General Devices Company, Inc. e-BridgeTM mobile application for EMS providers. The app allowed real-time communication and data transmission between EMS providers and the cardiac catheterization lab and emergency department staff. A single-center, retrospective observational study was conducted on 795 STEMI activations undergoing emergent coronary angiography between January 2017 and July 2020. After exclusions, sample size was determined to be 428. The implementation of the app occurred on May 14th, 2019, and EMS transmissions were utilized in 132 patient cases during the study period.

Results

The implementation of the application resulted in a significant reduction in D2B time by 7.2 minutes (61.2 minutes vs. 68.36 minutes, p=0.005, CI -12.2 to -2.14) and ED board time by 4.41 minutes (29.38 minutes vs. 24.98 minutes, p=0.01, CI -7.8 to -1). There was a trend towards a reduction in First Medical Contact to balloon time, although it was not statistically significant. Further analysis revealed that the application did not significantly reduce D2B time or First Medical Contact to balloon time during the day shift but had a significant improvement in these metrics during the night shift.

Conclusion

The implementation of app-based communication between EMS providers and in-hospital providers using GPS tracking resulted in statistically significant reductions in First Medical Contact to balloon time and D2B time at our institution. This approach holds promise in improving the timely management of STEMI patients, particularly during the night shift.
Dexmedetomidine decreases cerebral hyperperfusion incidence following carotid stenting: A randomized, double-blind trial
Authors: Chang Enqiang , Wu Lingzhi , Li Xinyi , Zhou Jinpeng , Zhi Hui , Sun Min , Chen Guanyu , Li Li , Li Tianxiao , Ma Daqing , Zhang Jiaqiang
Published: July 2023

Background

Cerebral hyperperfusion syndrome (CHS) is not a common but severe complication after carotid artery stenting (CAS). We investigated whether prophylactic low-dose dexmedetomidine, a selective α2-adrenoceptor agonist, can decrease cerebral hyperperfusion induced brain injury after carotid artery stenting.

Methods

This randomised, double-blind, placebo-controlled trial was conducted in a tertiary-care hospital in Zhengzhou, China. Patients aged 18 to 80 years old who had undergone CAS and from whom written informed consent was obtained, were enrolled between Jul 20, 2019 and Oct 10, 2022. Patients were randomly assigned to receive either intravenous dexmedetomidine (0·1 μg/kg/h, from insertion of the laryngeal mask until 72hr on postoperative day 3) (n = 80) or placebo (intravenous normal saline) (n = 80). The primary endpoint was the incidence of cerebral hyperperfusion (CH) and cerebral hyperperfusion syndrome (CHS), which were assessed six times with Transcranial Doppler sonography (TCD) during the postoperative three days. This study was registered with the Chinese Clinical Trial Registry,www.chictr.org.cn, ChiCTR1900024416.

Results

CH occurred in 30 (37·5%) of 80 patients given a placebo and in 9 (11·2%) of 80 patients given dexmedetomidine (odds ratio [OR] 0·211, 95% CI 0·09-0·48; p<0·001). Further, CHS was significantly lower in the Dex group than in the placebo group (2.5% vs 13·75%; [OR] 0·16, 95% CI 0·03-0·71; p=0·017). Correspondingly, dexmedetomidine significantly upregulated serum brain-derived neurotrophic factor (BDNF) and downregulated neuronal injury biomarker neurofilament light chain (Nfl). The hierarchical clustering analysis revealed little difference in lipids metabolites between the two groups pre- and post-operatively, with Dex treatment uniquely increased lysphosphatidylethanolamine (LPE).

Conclusions

A low prophylactic dose of dexmedetomidine significantly decreased the occurrence of cerebral hyperperfusion and cerebral hyperperfusion syndrome during the first three days after carotid artery stenting surgery.
Variegate expression of Cre recombinase in hematopoietic cells in CD11c-cre transgenic mice
Authors: Murat Claire , Guerder Sylvie
Published: July 2023

In this study, we performed an in-depth analysis of Cre expression in the widely used CD11c-Cre transgenic mice generated by the group of Boris Reizis. In contrast to previous observation, using the highly sensitive Rosa-26-floxed-tdTomato reporter mouse line, we show variegated expression of Cre in multiple hematopoietic linage cells starting in hematopoietic stem cells. We found that in the CD11c-Cre driver mice: (1) Cre is expressed in cDC linage cells and pDC starting from the myeloid dendritic cell precursor, as expected ; (2) Cre is expressed in a substantial fraction of hematopoietic stem cells and common lymphoid progenitors ; (3) Cre is expressed in more than 50% of all leukocytes. Hence, this study indicates that the reporter mice used to characterize Cre expression in Cre-driver mice should be selected with caution and considering the sensitivity of the reporter system. This study also suggests that the interpretation of some reports may need to be re-considered based on a careful evaluation of the cell type-specificity of Cre-mediated in their model.
Naturally segregating genetic variants contribute to thermal tolerance in aD. melanogaster model system
Authors: Williams-Simon Patricka A. , Oster Camille , Moaton Jordyn A. , Ghidey Ronel , Ng’oma Enoch , Middleton Kevin M. , Zars Troy , King Elizabeth G.
Published: July 2023

Thermal tolerance is a fundamental physiological complex trait for survival in many species. For example, everyday tasks such as foraging, finding a mate, and avoiding predation, are highly dependent on how well an organism can tolerate extreme temperatures. Understanding the general architecture of the natural variants of the genes that control this trait is of high importance if we want to better comprehend how this trait evolves in natural populations. Here, we take a multipronged approach to further dissect the genetic architecture that controls thermal tolerance in natural populations using the Drosophila Synthetic Population Resource (DSPR) as a model system. First, we used quantitative genetics and Quantitative Trait Loci (QTL) mapping to identify major effect regions within the genome that influences thermal tolerance, then integrated RNA-sequencing to identify differences in gene expression, and lastly, we used the RNAi system to 1) alter tissue-specific gene expression and 2) functionally validate our findings. This powerful integration of approaches not only allows for the identification of the genetic basis of thermal tolerance but also the physiology of thermal tolerance in a natural population, which ultimately elucidates thermal tolerance through a fitness-associated lens.
Assessment of population dynamics of endangeredT. putitora(Ham, 1822) in the breeding and nursery grounds of Western Himalaya
Authors: Rana Priyanka , Nautiyal Prakash
Published: July 2023

The present study analyzed the population characteristics ofTor putitorain their breeding and nursery grounds located in Western Himalayan region. From a sample size of 400 individuals, growth parameters such as asymptotic length, growth rate and growth performance index were estimated as 80.01 cm, 0.810 per year and 3.71 per year while the potential longevity was estimated as 4.6 years. The mortality parameters such as total, natural and fishing mortality were estimated as 2.88 /year, 1.05/ year and 1.83 / year respectively. The length at 25 %, 50% and 75% susceptibility to capture was estimated as 40.87 cm, 38.11 cm and 35.34 cm respectively. The fishing mortality and exploitation beyond optimum level and maximum sustainable exploitation ratio (Emax) indicate the overly exploitation of Mahseer resources in their breeding and nursery grounds. This indicates that the examined breeding and nursery grounds in Western Himalaya are facing intense “growth and recruitment overfishing” which may result in stock collapse in the forthcoming years.
In vitrobroad-spectrum antiviral activity of MIT-001, a mitochondria-targeted reactive oxygen species scavenger, against severe acute respiratory syndrome coronavirus 2 and multiple zoonotic viruses
Authors: Lim Taehun , Rajoriya Shivani , Kim Bohyeon , Natasha Augustine , Im Hyeonjoo , Shim Hyun Soo , Yoo Junsang , Kim Jong Woo , Lee Eun-Woo , Shin Hye Jin , Kim Soon Ha , Kim Won-Keun
Published: July 2023

The COVID-19 pandemic caused by SARS-CoV-2 becomes a serious threat to global health and requires the development of effective antiviral therapies. Current therapies that target viral proteins have limited efficacy with side effects. In this study, we investigated the antiviral activity of MIT-001, a small molecule reactive oxygen species (ROS) scavenger targeting mitochondria, against SARS-CoV-2 and other zoonotic virusesin vitro. The antiviral activity of MIT-001 was quantified by RT-qPCR and plaque assay. We also evaluated the functional analysis of MIT-001 by JC-1 staining to measure mitochondrial depolarization, total RNA sequencing to investigate gene expression changes, and immunoblot to quantify protein expression levels. The results showed that MIT-001 effectively inhibited the replication of B.1.617.2 and BA.1 strains, Zika virus, Seoul virus, and Vaccinia virus. Treatment with MIT-001 restored the expression of heme oxygenase-1 (HMOX1) and NAD(P)H: quinone oxidoreductase 1 (NqO1) genes, anti-oxidant enzymes reduced by SARS-CoV-2, to normal levels. The presence of MIT-001 also alleviated mitochondrial depolarization caused by SARS-CoV-2 infection. These findings highlight the potential of MIT-001 as a broad-spectrum antiviral compound that targets for zoonotic RNA and DNA viruses, providing a promising therapeutic approach to combat viral infection.
Nuclear envelope assembly relies on CHMP-7 in the absence of BAF-LEM-mediated hole closure
Authors: Barger Sarah R. , Penfield Lauren , Bahmanyar Shirin
Published: July 2023

Barrier-to-autointegration factor (BAF) is a DNA binding protein that crosslinks chromatin to assemble the nuclear envelope (NE) after mitosis. BAF also binds the Lap2b-Emerin-Man1 (LEM) domain family of NE proteins to repair interphase ruptures. The NE adaptors to ESCRTs, LEMD2-CHMP7, seal NE holes surrounding mitotic spindle microtubules (MTs), but whether NE hole closure in mitosis involves BAF-LEM binding is not known. Here, we analyze NE sealing after meiosis II inC. elegansoocytes to show that BAF-LEM binding and LEM-2LEMD2-CHMP-7 have distinct roles in hole closure around spindle MTs. LEM-2/EMR-1emerinfunction redundantly with BAF-1 to seal the NE. Compromising BAF-LEM binding revealed an additional role for EMR-1 in maintenance of the NE permeability barrier and an essential role for LEM-2-CHMP-7 in preventing NE assembly failure. The WH domain of LEM-2 recruits the majority of CHMP-7 to the NE inC. elegansand a LEM-2 -independent pool of CHMP-7, which is mostly enriched in the nucleoplasm, also contributes to NE stability. Thus, NE hole closure surrounding spindle MTs requires redundant mechanisms that safeguard against failure in NE assembly to support embryogenesis.
Selective endocytic uptake of targeted liposomes occurs within a narrow range of liposome diameter
Authors: Ashby Grant , Keng Kayla E. , Hayden Carl C. , Gollapudi Sadhana , Houser Justin R. , Jamal Sabah , Stachowiak Jeanne C.
Published: July 2023

Cell surface receptors facilitate signaling and nutrient uptake. These processes are dynamic, requiring receptors to be actively recycled by endocytosis. Due to their differential expression in disease states, receptors are often the target of drug-carrier particles, which are adorned with ligands that bind specifically to receptors. These targeted particles are taken into the cell by multiple routes of internalization, where the best-characterized pathway is clathrin-mediated endocytosis. Most studies of particle uptake have utilized bulk assays, rather than observing individual endocytic events. As a result, the detailed mechanisms of particle uptake remain obscure. To address this gap, we have employed a live-cell imaging approach to study the uptake of individual liposomes as they interact with clathrin-coated structures. By tracking individual internalization events, we find that the size of liposomes, rather than the density of the ligands on their surfaces, primarily determines their probability of uptake. Interestingly, targeting has the greatest impact on endocytosis of liposomes of intermediate diameters, with the smallest and largest liposomes being internalized or excluded, respectively, regardless of whether they are targeted. These findings, which highlight a previously unexplored limitation of targeted delivery, can be used to design more effective drug carriers.
Establishing thresholds for cytokine storm and defining their relationship to disease severity in respiratory viral infections
Authors: Souquette Aisha , Crawford Jeremy Chase , Wolf Joshua , Blair Ashley , Agrawal Mona , Boywid Laura , McNair Kristin , Hysmith Nicholas D. , Hundman Chloe , Bahadoran Azadeh , Arnold Sandra R. ,   SJTRC Study Team, Smallwood Heather S. , Green Amanda , Thomas Paul G.
Published: July 2023

Previous studies have identified cytokines associated with respiratory virus infection illness outcome. However, few studies have included comprehensive cytokine panels, longitudinal analyses, and/or simultaneous assessment across the severity spectrum. This, coupled with subjective definitions of cytokine storm syndrome (CSS), have contributed to inconsistent findings of cytokine signatures, particularly with COVID severity. Here, we measured 38 plasma cytokines and compared profiles in healthy, SARS-CoV-2 infected, and multisystem inflammatory syndrome in children (MIS-C) patients (n = 169). Infected patients spanned the severity spectrum and were classified as Asymptomatic, Mild, Moderate or Severe. Our results showed acute cytokine profiles and longitudinal dynamics of IL1Ra, IL10, MIP1b, and IP10 can differentiate COVID severity groups. Only 4% of acutely infected patients exhibited hypercytokinemia. Of these subjects, 3 were Mild, 3 Moderate, and 1 Severe, highlighting the lack of association between CSS and COVID severity. Additionally, we identified IL1Ra and TNFa as potential biomarkers for patients at high risk for long COVID. Lastly, we compare hypercytokinemia profiles across COVID and influenza patients and show distinct elevated cytokine signatures, wherein influenza induces the most elevated cytokine profile. Together, these results identify key analytes that, if obtained at early time points, can predict COVID illness outcome and/or risk of complications, and provide novel insight for improving the conceptual framework of hypercytokinemia, wherein CSS is a subgroup that requires concomitant severe clinical manifestations, and including a list of cytokines that can distinguish between subtypes of hypercytokinemia.
Comparative Reconstruction of SARS-CoV-2 transmission in three African countries using a mathematical model integrating immunity data
Authors: Naffeti Bechir , BenAribi Walid , Kebir Amira , Diara Maryam , Schoenhals Matthieu , Vigan-Womas Inès , Dellagi Koussay , BenMiled Slimane
Published: July 2023

Objectives

Africa has experienced fewer coronavirus disease 2019 (COVID-19) cases and deaths than other regions, with a contrasting epidemiological situation between countries, raising questions regarding the determinants of disease spread in Africa.

Method

We built a susceptible–exposed–infected–recovered model including COVID-19 mortality data where recovery class is structured by specific immunization and modeled by a partial differential equation considering the opposed effects of immunity decline and immunization. This model was applied to Tunisia, Senegal, and Madagascar.

Finding

Senegal and Tunisia experienced two epidemic phases. Initially, infections emerged in naive individuals and were limited by social distancing. Variants of concern (VOCs) were also introduced. The second phase was characterized by successive epidemic waves driven by new VOCs that escaped host immunity. Meanwhile, Madagascar demonstrated a different profile, characterized by longer intervals between epidemic waves, increasing the pool of susceptible individuals who had lost their protective immunity. The impact of vaccination in Tunisia and Senegal on model parameters was evaluated.

Interpretation

Loss of immunity and vaccination-induced immunity have played crucial role in controlling the African pandemic. Severe acute respiratory syndrome coronavirus 2 has become endemic now and will continue to circulate in African populations. However, previous infections provide significant protection against severe diseases, thus providing a basis for future vaccination strategies.
Risk Stratification of Advanced Fibrosis in HIV Patients With Hepatic Steatosis Using the NAFLD Fibrosis and BARD Scores
Authors: Yendewa George A. , Khazan Ana , Jacobson Jeffrey M.
Published: July 2023

Background

Nonalcoholic fatty liver disease (NAFLD) is increasingly prevalent in people with HIV (PWH), yet the risk factors for disease progression are poorly understood, due to inadequate surveillance. We employed non-invasive methods to estimate the prevalence and associated factors of advanced NAFLD in PWH.

Methods

We conducted a retrospective study of PWH enrolled in our clinic from 2005 to 2022. We employed imaging (ultrasound, computer tomography, magnetic resonance imaging, and transient elastography) or biopsy reports to identify cases of hepatic steatosis. We excluded patients with harmful alcohol use, hepatitis B or C infection, and other specified etiologies. We used the NAFLD Fibrosis Score (NFS), BARD Score, AST to Platelet Index (APRI), and Fibrosis-4 (FIB-4) Score to stratify fibrosis. We used logistic regression to identify predictors of advanced fibrosis.

Results

Among 3959 PWH in care, 1201 had available imaging or liver biopsies. After exclusions, 114 of the remaining 783 had evidence of hepatic steatosis (prevalence 14.6%). The majority were male (71.1%), with mean age 46.1 years, and mean body mass index (BMI) 31.4 ± 8.1 kg/m2. About 24% had lean NAFLD (BMI < 25 kg/m2). Based on the NFS, 27.2% had advanced fibrosis, which was corroborated by estimates from the other scores. In adjusted regression analysis, advanced fibrosis was associated with BMI > 35 kg/m2(4.43, 1.27-15.48), thrombocytopenia (4.85, 1.27-18.62) and hypoalbuminemia (9.01, 2.39-33.91).

Conclusion

We found a NAFLD prevalence of 14.6%, with 27.2% of cases having advanced fibrosis. Our study provides practical insights into the surveillance of NAFLD in PWH.
Impact of opioid overdoses on US life expectancy and years of life lost, by demographic group and stimulant co-involvement: a mortality data analysis from 2019-2022
Authors: Hébert Anne H. , Hill Alison L.
Published: July 2023

Background

The United States’ opioid crisis is worsening, and the number of deaths reached 81,806 in 2022 after more than tripling over the past decade. This study aimed to comprehensively characterize changes in burden of opioid overdose mortality in terms of life expectancy reduction and years of life lost between 2019-2022, including differential burden across demographic groups and the contribution of polysubstance use.

Methods

Using life tables and counts for all-cause and opioid overdose deaths from the National Center for Health Statistics, we constructed cause-eliminated life tables to estimate mortality by age in the absence of opioid-related deaths. We calculated the loss in life expectancy at birth (LLE) and total years of life lost (YLL) due to opioid overdose deaths by state of residency, sex, racial/ethnic group, and co-involvement of cocaine and psychostimulants.

Findings

Opioid-related deaths in the US led to an estimated 3·1 million years of life lost in 2022 (38 years per death), compared to 2·0 million years lost in 2019. Relative to a scenario with no opioid mortality, we estimate that opioid-related deaths reduced life expectancy nationally by 0·67 years in 2022 vs 0·52 years in 2019. This LLE worsened in all racial/ethnic groups during the study period: 0·76y to 0·96y for white men, 0·36y to 0·55y for white women, 0·59y to 1·1y for Black men, 0·27y to 0·53y for Black women, 0·31y to 0·82y for Hispanic men, 0·19y to 0·31y for Hispanic women, 0·62y to 1·5y for American Indian/Alaska Native (AI/AN) men, 0·43y to 1y for AI/AN women, 0·09y to 0·2y for Asian men, and 0.08y to 0.13y for Asian women. Nearly all states experienced an increase in years of life lost (YLL) per capita from 2019-2022, with YLL more than doubling in 16 states. Cocaine or psychostimulants with abuse potential (incl. methamphetamines) were involved in half of all deaths and years of life lost in 2022, with substantial variation in the predominant drug class by state and racial/ethnic group.

Interpretation

The burden of opioid-related mortality increased dramatically in the US between 2019-2022, coinciding with the period of the COVID-19 pandemic and the associated disruptions to social, economic, and health systems. Opioid overdose deaths are an important contributor to decreasing US life expectancy, and Black, Hispanic, and Native Americans now experience mortality burdens approaching or exceeding white Americans.

Funding

None
Low-cost, local production of a safe and effective disinfectant for resource-constrained communities
Authors: Naranjo-Soledad Andrea , Smesrud Logan , Bandaru Siva RS , Hernandez Dana , Mehare Meire , Mahmoud Sara , Matange Vijay , Rao Bakul , Chandana N , Balcom Paige , Omole David Olugbenga , Alvarez-Mejia Cesar , Lopez-Ramirez Varinia , Gadgil Ashok
Published: July 2023

Improved sanitation and hygiene depend on the accessibility and availability of effective disinfectant solutions. These disinfectant solutions are unavailable to many communities worldwide due to resource limitations, among other constraints. Safe and effective chlorine- based disinfectants can be produced via simple electrolysis of salt water, providing a low-cost and reliable option for on-site, local production of disinfectant solutions to improve sanitation and hygiene. We report on a system (herein called “Electro-Clean”) that can produce concentrated solutions of hypochlorous acid (HOCl) using only low-cost and now widely accessible materials. Using only table salt, water, graphite welding rods, and a DC power supply, HOCl solutions (∼1.5 liters) of 0.1% free chlorine (i.e. 1000 ppm) can be safely produced in less than two hours at low potential (5 V DC) and modest current (∼5 A). Rigorous testing of free chlorine production and durability of the Electro-Clean system components, described here, have been verified to work in multiple locations around the world by our project team, including microbiological tests conducted in two different countries to confirm the biocidal efficacy of the Electro-Clean solution as a surface disinfectant. We provide cost estimates for making HOCl locally with this method in the USA, India, and Mexico. Our findings show that Electro-Clean is an affordable alternative to off-the-shelf commercial chlorinator systems in terms of first costs (or capital costs), and cost-competitive relative to the unit cost of the disinfectant produced. By minimizing dependence on supply chains and allowing for local production, the Electro-Clean production process has the potential for improving public health by addressing the need for high- strength disinfectant solutions in resource-constrained communities.
Clinical outcomes after the introduction of dolutegravir for second-line antiretroviral therapy in South Africa: a retrospective cohort study
Authors: Asare Kwabena , Sookrajh Yukteshwar , van der Molen Johan , Khubone Thokozani , Lewis Lara , Lessells Richard J , Naidoo Kogieleum , Sosibo Phelelani , van Heerden Rosemary , Garrett Nigel , Dorward Jienchi
Published: July 2023

Background

Dolutegravir is now recommended for second-line anti-retroviral therapy (ART) in low- and middle-income countries. We compared outcomes with dolutegravir (DTG) versus the previous lopinavir/ritonavir (LPV/r) regimen in South Africa.

Methods

We used routinely collected, de-identified data from 59 South African clinics. We included people living with HIV aged ≥ 15 years with virologic failure (two consecutive viral loads ≥1000 copies/mL) on first-line tenofovir disoproxil fumarate (TDF)-based ART and switched to second-line ART. We used modified Poisson regression models to compare outcomes of 12-month retention-in-care and viral suppression (<50 copies/ml) after switching to second-line regimens of zidovudine (AZT), emtricitabine/lamivudine (XTC), DTG and TDF/XTC/DTG and AZT/XTC/LPV/r.

Findings

Of 1214 participants, 729 (60.0%) were female, median age was 36 years (interquartile range 30 to 42), 689 (56.8%) were switched to AZT/XTC/LPV/r, 217 (17.9%) to AZT/XTC/DTG and 308 (25.4%) to TDF/XTC/DTG. Retention-in-care was higher with AZT/XTC/DTG (85.7%, adjusted risk ratio (aRR) 1.14, 95% confidence interval (CI) 1.03 to 1.27; adjusted risk difference (aRD) 10.89%, 95%CI 2.01 to 19.78) but not different with TDF/XTC/DTG (76.9%, aRR 1.01, 95%CI 0.94 to 1.10; aRD 1.04%, 95%CI -5.03 to 7.12) compared to AZT/XTC/LPV/r (75.2%). Retention-in-care with TDF/XTC/DTG was not statistically significantly different from AZT/XTC/DTG (aRR 0.89, 95%CI 0.78 to 1.01; aRD - 9.85%, 95%CI -20.33 to 0.63). Of 799 participants who were retained-in-care with a 12-month viral load, viral suppression was higher with AZT/XTC/DTG (59.3%, aRR 1.25, 95%CI 1.06 to 1.47; aRD 11.57%, 95%CI 2.37 to 20.76) and TDF/XTC/DTG (60.7%, aRR 1.30, 95%CI 1.14 to 1.48; aRD 14.16%, 95%CI 7.14 to 21.18) than with the AZT/XTC/LPV/r regimen (46.7%).

Interpretation

DTG-based second-line regimens were associated with similar or better retention-in-care and better viral suppression than the LPV/r-based regimen. TDF/XTC/DTG had similar viral suppression compared to AZT/XTC/DTG.

Funding

Bill & Melinda Gates Foundation, Africa Oxford Initiative.
Effects of time management interventions on mental health and wellbeing factors: A protocol for a systematic review
Authors: Young Anna Navin , Burke Aoife , Foley Sarah , Di Blasi Zelda
Published: July 2023

Background

Poor employee mental health and wellbeing are highly prevalent and costly. Time-related factors such as work intensification and perceptions of time poverty or pressure pose risks to employee health and wellbeing. While reviews suggest that there are positive associations between time management behavior and wellbeing, there is limited rigorous and systematic research examining the effectiveness of time management interventions on wellbeing in the workplace. A thorough review is needed to synthesize time management interventions and their effectiveness to promote employee mental health and wellbeing.

Method

A systematic search will be conducted using the following databases: PsychINFO via OVID (1806-Present), Web of Science, Scopus via Elsevier (1976-Present), Academic Search Complete (EBSCO), Cochrane Library via Wiley (1992-Present), and MEDLINE via OVID (1946-Present). The review will include experimental and quasi-experimental studies that evaluate the effects of time management interventions on wellbeing outcomes on healthy adults in a workplace context. Only studies in English will be included. Two authors will independently perform the literature search, record screening, data extraction, and quality assessment of each study included in the systematic review and meta-analysis. Data will be critically appraised using the Cochrane risk-of-bias tools. Depending on the data, a meta-analysis or a narrative synthesis will be conducted. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed in the development of this protocol. The protocol has been registered in PROSPERO (CRD4202125715).

Discussion

This review will provide systematic evidence on the effects of time management interventions on wellbeing outcomes in the workplace. It will contribute to our understanding of how time management approaches may help to address growing concerns for employee mental health and wellbeing.
A novel approach to classification and segmentation of colon cancer imaging towards personalized medicine
Authors: Harikrishnan Keerthi , Botelho Neil , Rebelo Penjo , Kenkre Amit , Tarcar Amogh
Published: July 2023

Recent advances in the field of pathology coupled with the rapid evolution of machine learning based techniques have revolutionized healthcare practices. Colorectal cancer accounts for one of the top 5 cancers with high incidence (126,240 in 2020) with a high mortality worldwide [1] [2]. Tissue biopsy remains to be the gold standard procedure for accurate diagnosis, treatment planning and prognosis prediction [3]. As an image based modality, pathology has attracted a lot of attention for development of AI algorithms and there has been a steady increase in the number of filings for FDA authorized use of AI algorithms in clinical practice [4]. The SemiCOL Challenge aims to develop computational pathology methods for automatic segmentation and classification of tumor and other tissue classes using H&E stained images. In this paper, we present a novel machine learning framework addressing the SemiCOL Challenge, focusing on semantic segmentation, segmentation-based whole-slide image classification, and effective use of limited annotated data. Our approach leverages deep learning techniques and incorporates data augmentation to improve the accuracy and efficiency of tumor tissue detection and classification in CRC. The proposed method achieves an average Dice score of 0.2785 for segmentation and an AUC score of 0.71 for classification across 20 whole-slide images. This framework has the potential to revolutionize the field of computational pathology, contributing to more efficient and accurate diagnostic tools for colorectal cancer.
Growth patterns and ratios of posterior cranial fossa structures in the Japanese pediatric population: A study utilizing CT scans
Authors: Hashimoto Hiroaki , Takemoto Osamu , Chiba Yasuyoshi
Published: July 2023

Purpose

The changes in the proportion of posterior cranial fossa structures during pediatric development remain unclear. This retrospective study aimed to investigate the growth patterns and ratios of these structures using computed tomography (CT) scans.

Methods

Head CT scans of pediatric patients with minor head trauma from our institute between March 2006 and May 2023 were analyzed. The study segmented the intracranial volume (ICV), posterior cranial fossa volume (PCFV), cerebellum volume (CBMV), and brainstem volume (BSV). Correlation coefficients were calculated among the parameters. Patients aged 0 to 10 years were divided into 15 age-related clusters, and mean and standard deviation values were measured. Growth curves were created by plotting mean values sequentially. Ratios such as PCFV/ICV and (CBMV + BSV)/PCFV were examined. Statistical analyses, including unpaired T-tests and logarithmic curve fitting, were performed.

Results

A total of 234 CT scans (97 from females, 115 from infants under one year of age) were analyzed. Positive correlations were observed among the parameters, with the strongest between PCFV and CBMV. The growth curves for ICV, PCFV, CBMV, and BSV exhibited a two-phase process, with rapid growth until approximately 4 years of age, followed by stabilization. The ratios PCFV/ICV and (CBMV + BSV)/PCFV showed increasing trends from birth onwards, stabilizing by 4 and one years of age, respectively.

Conclusion

This study provides insights into the growth patterns and ratios of posterior cranial fossa structures in the pediatric population. The findings demonstrate a two-phase growth process and increasing trends in the examined ratios.
Phenotypic and Genetic Characteristics of Retinal Vascular Parameters and their Association with Diseases
Authors: Vela Sofía Ortín , Beyeler Michael J. , Trofimova Olga , Iuliani Ilaria , Quiros Jose D. Vargas , de Vries Victor A. , Meloni Ilenia , Elwakil Adham , Hoogewoud Florence , Liefers Bart , Presby David , Ramdas Wishal D. , Tomasoni Mattia , Schlingemann Reinier , Klaver Caroline C.W. , Bergmann Sven
Published: July 2023

Fundus images allow for non-invasive assessment of the retinal vasculature whose features provide important information on health. Using a fully automated image processing pipeline, we extracted 17 different morphological vascular phenotypes, including median vessels diameter, diameter variability, main temporal angles, vascular density, central retinal equivalents, the number of bifurcations, and tortuosity, from over 130k fundus images of close to 72k UK Biobank subjects. We performed Genome-Wide Association Studies of these phenotypes. From this, we estimated their heritabilities, ranging between 5 and 25%, and genetic cross-phenotype correlations, which mostly mirrored the corresponding phenotypic correlations, but tended to be slightly larger. Projecting our genetic association signals onto genes and pathways revealed remarkably low overlap suggesting largely decoupled mechanisms modulating the different phenotypes. Our disease phenotype associations confirmed some previously known findings and revealed many novel connections. Notably, diameter variability, especially for the veins, seems to have new and interesting associations with diseases, including heart attack, pulmonary embolism, and age of death. Mendelian Randomization analysis suggests a causal influence of blood pressure and body mass index on retinal vessel morphology, among other results. We validated key findings in two independent smaller cohorts. Our analyses provide evidence that large-scale analysis of image-derived vascular phenotypes has sufficient power for obtaining functional, as well as some initial causal insights into the processes modulating the retinal vasculature.
Immune-Neuroendocrine Patterning and Response to Stress. A latent profile analysis in the English Longitudinal Study of Ageing
Authors: Hamilton Odessa S. , Iob Eleonora , Ajnakina Olesya , Kirkbride James B. , Steptoe Andrew
Published: July 2023

Psychosocial stress exposure can disturb communication signals between the immune, nervous, and endocrine systems that are intended to maintain homeostasis. This dysregulation can provoke a negative feedback loop between each system that has high pathological risk. Here, we explore patterns of immune-neuroendocrine activity and the role of stress. Using data from the English Longitudinal Study of Ageing (ELSA), we first identified the latent structure of immune-neuroendocrine activity (indexed by high sensitivity C-reactive protein [CRP], fibrinogen [Fb], hair cortisol [cortisol], and insulin growth-factor-1 [IGF-1]), within a population-based cohort using latent profile analysis (LPA). Then, we determined whether life stress was associated with membership of different immune-neuroendocrine profiles. We followed 4,934 male and female participants with a median age of 65 years over a four-year period (2008-2012). A three-class LPA solution offered the most parsimonious fit to the underlying immune-neuroendocrine structure in the data, with 36%, 40%, and 24% of the population belonging to profiles 1 (low-risk), 2 (moderate-risk), and 3 (high-risk), respectively. After adjustment for genetic predisposition, sociodemographics, lifestyle, and health, higher exposure to stress was associated with a 61% greater risk of belonging to thehigh-riskprofile (RRR: 1.61; 95%CI=1.23-2.12,p=0.001), but not themoderate-riskprofile (RRR=1.10, 95%CI=0.89-1.35,p=0.401), as compared with thelow-riskprofile four years later. Our findings extend existing knowledge on psychoneuroimmunological processes, by revealing how inflammation and neuroendocrine activity cluster in a representative sample of older adults, and how stress exposure was associated with immune-neuroendocrine responses over time.
Variational autoencoders to predict DNA-methylation age and provide biological insights in age-related health and disease
Authors: Steyaert Sandra , Verhelle Adriaan , Criekinge Wim Van
Published: July 2023

Motivation

Epigenetic ageing clocks based on age-associated changes in DNA-methylation (DNAm) profiles have shown great potential as predictors to quantify age-related health and disease. Most of these clocks are built using penalized linear regression models with the aim to predict chronological and/or biological age. However, the precise underlying biological mechanisms influencing these clocks remain unclear. In this work, we explored if a Variational Autoencoder (VAE) can be trained to model DNAm age, and whether this VAE captures biologically relevant features of ageing in the latent space.

Results

Our results indicate that VAEs present a promising framework to construct embeddings that capture complex interactions and that can be used to extract biological meaningful features upon predicting DNAm age. By using deep learning interpretation methods, we show it is possible to determine which genomic loci and pathways are important in making the predictions, both on a population and individual level, paving the way to unravel what makes the DNAm clock tick.
Appropriateness of ChatGPT in answering heart failure related questions
Authors: King Ryan C. , Samaan Jamil S. , Yeo Yee Hui , Mody Behram , Lombardo Dawn M. , Ghashghaei Roxana
Published: July 2023

Introduction

Heart failure requires complex management with increased patient knowledge shown to improve outcomes. This study assessed the knowledge of Chat Generative Pre-Trained Transformer (ChatGPT) and its appropriateness as a supplemental resource of information for patients with heart failure.

Materials and Methods

A total of 107 frequently asked heart failure-related questions were included. Responses were generated using GPT-3.5 and GPT-4. The accuracy and reproducibility of responses were graded by two reviewers board-certified in cardiology, with differences resolved by a third reviewer board-certified in cardiology and advanced heart failure. Accuracy was graded using a four-point scale: 1) Comprehensive 2) Correct but inadequate 3) Some correct and some incorrect 4) Completely incorrect.

Results

GPT-4 displayed a greater proportion of comprehensive knowledge for the categories of “basic knowledge” and “management” (89.8%, 82.9%). GPT-3.5 performed best in the “management” and “other” category (prognosis, procedures, and support) (78.1%, 94.1%). There were two total responses (1.9%) graded as “some correct and incorrect” for GPT-3.5, while no “completely incorrect” responses were produced. The models also provided highly reproducible responses, with GPT-3.5 scoring above 94% in every category and GPT-4 with 100% for all answers.

Conclusions

GPT-3.5 and GPT-4 answered the majority of heart failure-related questions accurately and reliably. ChatGPT may lead to better outcomes in patients with heart failure by providing accessible and easy to understand health education. However, in its current state the model necessitates further rigorous testing and validation to ensure patient safety and equity across all patient demographics.
Causal associations between type 1 diabetes mellitus and cardiovascular diseases: A Mendelian randomization study
Authors: Liu Zirui , Wang Haocheng , Yang Zhengkai , Lu Yu , Zou Cao
Published: July 2023

Background

The presence of type 1 diabetes mellitus (T1DM) has been demonstrated to pose an increased risk for developing cardiovascular diseases (CVDs). However, the causal relationships between T1DM and CVDs remain unclear due to the uncontrolled confounding factors and reverse causation bias of the observational studies.

Aim

To investigate the causal relationships between T1DM and seven major CVDs, including myocardial infarction (MI), heart failure (HF), coronary artery disease (CAD), atrial fibrillation (AF), coronary atherosclerosis, peripheral atherosclerosis, and stroke, using a two-sample bidirectional Mendelian randomization (MR) method.

Method

We selected genetic instruments for T1DM and the seven CVDs from the largest available genome-wide association studies (GWAS) of European ancestry for the MR analysis. Three complementary methods: inverse variance weighted (IVW), weighted median, and MR-Egger were used for the MR estimates. The potential pleiotropic effects were assessed by MR-Egger intercept and MR-PRESSO global test. Additionally, multivariable MR (MVMR) analysis was performed to examine whether T1DM has independent effects on CVDs with adjustment of potential confounding factors. Moreover, a two-step MR approach was used to assess the potential mediating effects of these factors on the causal effects between T1DM and CVDs.

Results

Causal effects of T1DM on peripheral atherosclerosis (odds ratio [OR]=1.06, 95% confidence interval [CI]: 1.02–1.10;p= 0.002)] and coronary atherosclerosis (OR=1.03, 95% CI: 1.01–1.05;p= 0.001) were found. The results were less likely to be biased by the horizontal pleiotropic effects (both p values of MR-Egger intercept and MR-PRESSO Global test > 0.05). In the following MVMR analysis, we found the causal effects of T1DM on peripheral atherosclerosis and coronary atherosclerosis remain significant after adjusting for a series of potential confounding factors. Moreover, we found that hypertension partly mediated the causal effects of T1DM on peripheral atherosclerosis (proportion of mediation effect in total effect: 11.47%, 95% CI: 3.23%–19.71%) and coronary atherosclerosis (16.84%, 95% CI: 5.35%–28.33%). We didn’t find significant causal relationships between T1DM and other CVDs, including MI, CAD, HF, AF, or stroke. For the reverse MR from CVD to T1DM, no significant causal relationships were identified.

Conclusion

This MR study provided evidence supporting the causal effect of T1DM on peripheral atherosclerosis and coronary atherosclerosis, with hypertension partly mediating this effect.
The association between clonal hematopoiesis driver mutations, immune cell function and the vasculometabolic complications of obesity
Authors: Tercan Helin , Cossins Benjamin , van Deuren Rosanne , Rutten Joost H.W. , Joosten Prof. Leo A.B. , Netea Prof. Mihai G. , Hoischen Alexander , Bekkering Siroon , Riksen Prof. Niels P.
Published: July 2023

Background

Obesity is accompanied by dysregulated inflammation, which can contribute to vasculometabolic complications, including metabolic syndrome and atherosclerosis. Recently, clonal hematopoiesis of indeterminate potential (CHIP) has emerged as a risk factor for cardiovascular diseases. We aimed to determine how CHIP related to immune cell function, systemic inflammation, and vasculometabolic complications in obese individuals.

Methods

297 individuals with overweight and obesity, between the ages of 54 and 81, were recruited in a cross-sectional study. Clonal Hematopoiesis Driver Mutations (CHDMs) were identified with an ultrasensitive targeted assay. Assesment of carotid artery atherosclerosis was performed with ultrasound. Detailed immunological parameters were studied. Adipose tissue inflammation was determined in subcutenous fat biopsies.

Results

Individuals with CHIP had higher concentrations of circulating IL-6. Total number of leukocytes and neutrophils were higher in individuals with CHIP. In contrast,ex vivocytokine production capacity of PBMCs was significantly lower in individuals with CHIP. Sex stratified analysis showed that men with CHDMs had significantly higher leukocyte and neutrophil counts andex vivocytokine production capacity was lower in women with CHDMs. Surprisingly, the presence of atherosclerotic plaques was significantly lower in individuals with CHDMs. There was no relation between CHIP and metabolic syndrome.

Conclusion

In individuals with overweight or obesity, CHDMs are not associated with vasculometabolic complications, but rather with a lower presence of carotid plaques. CHDMs associate with increased circulating inflammatory markers and leukocyte numbers, but a lower PBMC cytokine production capacity.