bluuebunny/crossref_metadata_2025 huggingface dataset:
Does destination make a difference? Outcomes after a policy change affecting cutoff times for prehospital transport
Authors: Renaud Elizabeth , Cummings Olivia , Vanover Melissa , Tanzer Joshua Ray , McCarthy Andrew
Published: January 2024

BACKGROUND

Facilitating primary triage and care at pediatric trauma centers (PTCs) can improve outcomes for children after trauma. However, scene location and regional emergency medical services regulations may result in initial evaluation occurring at nonpediatric facilities with later transportation to PTCs for definitive care. In this study, we assessed the results of a change in transport time cutoff from 30 to 45 minutes on pediatric patient outcomes.

METHODS

After institutional review board approval, the Pediatric Trauma Database at a level 1 PTC was queried for patients seen before (January 1, 2015, to December 31, 2017) and after (January 1, 2018, to December 31, 2020) the implementation of a policy increasing transport cutoff time from 30 to 45 minutes. Patient outcomes were compared by transport status and Injury Severity Score (ISS) using generalized linear regression analysis.

RESULTS

A total of 505 patients were seen before policy changes, and 413 patients, after policy changes. Both groups had similar numbers of severely injured patients (ISS, ≥15; pre, 64 [13%]; post, 61 [15%]). Average transport time increased after change (pre, 20 minutes [95% confidence interval, 18–22 minutes]; post, 29 minutes [95% confidence interval, 26–33 minutes]; p = 0.0252), consistent with policy compliance. The proportion of transferred patients did not change after policy implementation (p = 0.5856), and the complications among all patients with an ISS of ≥15 did not significantly decrease (pre, 75%; post, 65.6%). However, those patients with an ISS of ≥15 admitted directly from the scene had a lower frequency of complications after the policy changes (pre, 76%; post, 59%; p = 0.0319), and in the postperiod, transferred patients with an ISS of ≥15 had a higher complication rate than those admitted directly from the scene (p < 0.0001).

CONCLUSION

Direct scene admission to a PTC is associated with a lower complication profile for patients with higher ISS. Methods to ensure adherence to cutoff thresholds for emergency medical services transport may have a positive benefit on patient outcomes.

LEVEL OF EVIDENCE

Prognostic and Epidemiological; Level IV.
Clinical Research in Renal Transplantation: A Bibliometric Perspective on a Half-century of Innovation and Progress
Authors: Jiang Decan , Mantas Anna , Studier-Fischer Alexander , Fuchs Juri , Uluk Deniz , Loos Martin , Mieth Markus , Zeier Martin , Husen Peri , Golriz Mohammad , Kahlert Christoph , Ryschich Eduard , Mehrabi Arianeb , Pratschke Johann , Michalski Christoph W. , Czigany Zoltan
Published: January 2024

Background.

Groundbreaking biomedical research has transformed renal transplantation (RT) into a widespread clinical procedure that represents the mainstay of treatment for end-stage kidney failure today. Here, we aimed to provide a comprehensive bibliometric perspective on the last half-century of innovation in clinical RT.

Methods.

The Web of Science Core Collection was used for a comprehensive screening yielding 123 303 research items during a 50-y period (January 1973–October 2022). The final data set of the 200 most-cited articles was selected on the basis of a citation-based strategy aiming to minimize bias.

Results.

Studies on clinical and immunological outcomes (n = 63 and 48), registry-based epi research (n = 38), and randomized controlled trials (n = 35) dominated the data set. Lead US authors have signed 110 of 200 articles. The overall level of evidence was high, with 84% of level1 and -2 reports. Highest numbers of these articles were published in New England Journal of Medicine, Transplantation, and American Journal of Transplantation. Increasing trend was observed in the number of female authors in the postmillennial era (26% versus 7%).

Conclusions.

This study highlights important trends in RT research of the past half-century. This bibliometric perspective identifies the most intensively researched areas and shift of research interests over time; however, it also describes important imbalances in distribution of academic prolificacy based on topic, geographical aspects, and gender.
Potential and Uncertainties of RejectClass in Acute Kidney Graft Dysfunction: An Independent Validation Study
Authors: von Samson-Himmelstjerna Friedrich A. , Kakavand Nassim , Gleske Charlotte , Schraml Florian , Basta Agathe A. , Braunisch Matthias C. , Bräsen Jan H. , Schmitz Jessica , Kraus Daniel , Weinmann-Menke Julia , Zacharias Helena U. , Vaulet Thibaut , Naesens Maarten , Krautter Markus , Schwenger Vedat , Esser Grit , Kolbrink Benedikt , Amann Kerstin , Holzmann-Littig Christopher , Echterdiek Fabian , Kunzendorf Ulrich , Renders Lutz , Schulte Kevin , Heemann Uwe ,   on behalf of the TRABIO study group
Published: January 2024

Background.

Kidney graft rejections are classified based on the Banff classification. The RejectClass algorithm, initially derived from a cohort comprising mostly protocol biopsies, identifies data-driven phenotypes of acute rejection and chronic pathology using Banff lesion scores. It also provides composite scores for inflammation activity and chronicity. This study independently evaluates the performance of RejectClass in a cohort consisting entirely of indication biopsies.

Methods.

We retrospectively applied RejectClass to 441 patients from the German TRABIO (TRAnsplant BIOpsies) cohort who had received indication biopsies. The primary endpoint was death-censored graft failure during 2 y of follow-up.

Results.

The application of RejectClass to our cohort demonstrated moderately comparable phenotypic features with the derivation cohort, and most clusters indicated an elevated risk of graft loss. However, the reproduction of all phenotypes and the associated risks of graft failure, as depicted in the original studies, was not fully accomplished. In contrast, adjusted Cox proportional hazards analyses substantiated that both the inflammation score and the chronicity score are independently associated with graft loss, exhibiting hazard ratios of 1.7 (95% confidence interval, 1.2-2.3; P = 0.002) and 2.2 (95% confidence interval, 1.8-2.6; P < 0.001), respectively, per 0.25-point increment (scale: 0.0–1.0).

Conclusions.

The composite inflammation and chronicity scores may already have direct utility in quantitatively assessing the disease stage. Further refinement and validation of RejectClass clusters are necessary to achieve more reliable and accurate phenotyping of rejection.
Instructing somebody else to act: motor co-representations in the instructor
Authors: Van der Biest Mathias , Pedinoff Rebecca , Verbruggen Frederick , Brass Marcel , Kuhlen Anna K.
Published: January 2024

Instructions enable humans to perform novel tasks quickly. This is achieved by creating and activating the instruction representation for upcoming tasks, which can then modulate ongoing task behaviour in an almost ‘reflexive’ manner, an effect called instruction-based reflexivity. While most research has focused on understanding how verbal instructions are represented within the ‘instructed’ (i.e. the person receiving instructions), here we focus on how the instructor's (i.e. the person giving instructions) behaviour is affected through instructing. In a series of three experiments and one pooled analysis, we extended the classical instruction-based reflexivity paradigm to a novel social variant in which the instructions are given by an instructor (rather than visual computer-generated instructions). We found an instruction-based reflexivity effect for the instructor, that is, the instructor's task performance was better on congruent compared to incongruent trials (i.e. Experiments 1 and 2, pooled analysis). This suggests that the instructor represents the instructions of the instructed in an action-oriented format. However, this did not depend on the specific task of the instructed (i.e. Experiment 1), nor is it exclusively social (i.e. Experiment 3).
Sperm whale clans and human societies
Authors: Whitehead Hal
Published: January 2024

Sperm whale society is structured into clans that are primarily distinguished by vocal dialects, which may be symbolic markers of clan identity. However, clans also differ in non-vocal behaviour. These distinctive behaviours, as well as clan membership itself, are learned socially, largely within matrilines. The clans can contain thousands of whales and span thousands of kilometres. Two or more clans typically use an area, but the whales only socialize with members of their own clan. In many respects the closest parallel may be the ethno-linguistic groups of humans. Patterns and processes of human prehistory that may be instructive in studying sperm whale clans include: the extreme variability of human societies; no clear link between modes of resource acquisition and social structure; that patterns of vocalizations may not map well onto other behavioural distinctions; and that interacting societies may deliberately distinguish their behaviour (schismogenesis). Conversely, while the two species and their societies are very different, the existence of very large-scale social structures in both sperm whales and humans supports some primary drivers of the phenomenon that are common to both species (such as cognition, cooperation, culture and mobility) and contraindicates others (e.g. tool-making and syntactic language).
No detectable fitness cost of infection by cell-fusing agent virus in
Aedes aegypti
mosquitoes
Authors: Suzuki Yasutsugu , Suzuki Takahiro , Miura Fuminari , Reyes Jerica Isabel L. , Asin Irish Coleen A. , Mitsunari Wataru , Uddin Mohammad Mosleh , Sekii Yu , Watanabe Kozo
Published: January 2024

Aedes
mosquitoes are well-known vectors of arthropod-borne viruses (arboviruses). Mosquitoes are more frequently infected with insect-specific viruses (ISVs) that cannot infect vertebrates. Some ISVs interfere with arbovirus replication in mosquito vectors, which has gained attention for potential use against arbovirus transmission. Cell-fusing agent virus (CFAV), a widespread ISV, can reduce arbovirus dissemination in
Ae. aegypti
. However, vectorial capacity is largely governed by other parameters than pathogen load, including mosquito survival and biting behaviour. Understanding how ISVs impact these mosquito fitness-related traits is critical to assess the potential risk of using ISVs as biological agents. Here, we examined the effects of CFAV infection on
Ae. aegypti
mosquito fitness. We found no significant reduction in mosquito survival, blood-feeding behaviour and reproduction, suggesting that
Ae. aegypti
is tolerant to CFAV. The only detectable effect was a slight increase in human attraction of CFAV-infected females in one out of eight trials. Viral tolerance is beneficial for introducing CFAV into natural mosquito populations, whereas the potential increase in biting activity must be further investigated. Our results provide the first insight into the link between ISVs and
Aedes
mosquito fitness and highlight the importance of considering all aspects of vectorial capacity for arbovirus control using ISVs.
The Medusa effect: a registered replication report of Will, Merritt, Jenkins and Kingstone (2021)
Authors: Han Jing , Zhang Minjun , Liu Jiaxin , Song Yu , Yamada Yuki
Published: January 2024

Willet al.'s (2021Proc. Natl Acad. Sci. USA118, e2106640118 (doi:10.1073/pnas.2106640118)) found the Medusa effect, which refers to the tendency that people evaluate a ‘person in picture' more mindful than a ‘person in picture of a picture'. The present study tried to directly replicate the Experiments 2 and 5 of Willet al.'s (2021), to examine the reliability, validity and generalization of the Medusa effect, as well as its effect on prosocial behaviour. We used the same stimuli and methodology as the original research, but recruited participants in Japan with a larger sample size (N= 1387 in total) as a registered report. In our two replication experiments, we again found that pictures with lower levels of abstraction (L1) were perceived to convey more mind and lead to higher levels of prosocial behaviour, successfully replicating the original findings. The results of the present study suggested the high reproducibility and generalizability of the Medusa effect. Pre-registered Stage 1 protocol:https://osf.io/xj46z(date of in-principle acceptance: 9 February 2023)
Pushing coarse-grained models beyond the continuum limit using equation learning
Authors: VandenHeuvel Daniel J. , Buenzli Pascal R. , Simpson Matthew J.
Published: January 2024

Mathematical modelling of biological population dynamics often involves proposing high-fidelity discrete agent-based models that capture stochasticity and individual-level processes. These models are often considered in conjunction with an approximate coarse-grained differential equation that captures population-level features only. These coarse-grained models are only accurate in certain asymptotic parameter regimes, such as enforcing that the time scale of individual motility far exceeds the time scale of birth/death processes. When these coarse-grained models are accurate, the discrete model still abides by conservation laws at the microscopic level, which implies that there is some macroscopic conservation law that can describe the macroscopic dynamics. In this work, we introduce an equation learning framework to find accurate coarse-grained models when standard continuum limit approaches are inaccurate. We demonstrate our approach using a discrete mechanical model of epithelial tissues, considering a series of four case studies that consider problems with and without free boundaries, and with and without proliferation, illustrating how we can learn macroscopic equations describing mechanical relaxation, cell proliferation, and the equation governing the dynamics of the free boundary of the tissue. While our presentation focuses on this biological application, our approach is more broadly applicable across a range of scenarios where discrete models are approximated by approximate continuum-limit descriptions.
Effective population size mediates the impact of pollination services on pollen limitation
Authors: Cisternas-Fuentes Anita , Koski Matthew H.
Published: January 2024

Inadequate pollen receipt limits flowering plant reproduction worldwide. Ecological causes of pollen limitation (PL), like pollinator scarcity and low plant abundance, have been a primary research focus. The genetic diversity of plant populations could impact both quantity and quality components of PL in concert with ecological factors, yet empirical examples are lacking. We evaluated joint effects of ecological factors (flower abundance, pollinator visitation) and genetic effective population size (

N
E

) on PL across 13 populations of the common herb
Argentina anserina
. We used a histological approach with 5504 styles from 1137 flowers to separate quantity and quality components of PL, and link these to reproductive output.

N
E

and pollinator visitation interacted to shape PL, but

N
E

had stronger direct effects. Effectively smaller populations experienced stronger quantity PL, and controlled crosses in a pollinator-free environment revealed that stigmatic pollen quantity was an intrinsic population-level attribute that increased with

N
E

. Pollinator visitation enhanced pollen quality, but only in effectively larger populations. Quantity and quality PL negatively impacted fruit and seed set, respectively. Results highlight that PL is dictated by plant population genetic diversity in addition to commonly evaluated ecological factors. Efforts to support pollinators will more strongly enhance plant reproduction in genetically diverse populations.
Nest architecture influences host use by avian brood parasites and is shaped by coevolutionary dynamics
Authors: Hauber Mark E. , Nagy Jenő , Sheard Catherine , Antonson Nicholas D. , Street Sally E. , Healy Susan D. , Lala Kevin N. , Mainwaring Mark C.
Published: January 2024

Brood (social) parasites and their hosts exhibit a wide range of adaptations and counter-adaptations as part of their ongoing coevolutionary arms races. Obligate avian brood parasites are expected to use potential host species with more easily accessible nests, while potential hosts are expected to evade parasitism by building more concealed nests that are difficult for parasites to enter and in which to lay eggs. We used phylogenetically informed comparative analyses, a global database of the world's brood parasites, their host species, and the design of avian host and non-host nests (approx. 6200 bird species) to examine first, whether parasites preferentially target host species that build open nests and, second, whether host species that build enclosed nests are more likely to be targeted by specialist parasites. We found that species building more accessible nests are more likely to serve as hosts, while host species with some of the more inaccessible nests are targeted by more specialist brood parasites. Furthermore, evolutionary-transition analyses demonstrate that host species building enclosed nests frequently evolve to become non-hosts. We conclude that nest architecture and the accessibility of nests for parasitism represent a critical stage of the ongoing coevolutionary arms race between avian brood parasites and their hosts.
Stress-induced loss of social resilience in honeybee colonies and its implications on fitness
Authors: Ulgezen Zeynep N. , Van Langevelde Frank , van Dooremalen Coby
Published: January 2024

Stressors may lead to a shift in the timing of life-history events of species, causing a mismatch with optimal environmental conditions, potentially reducing fitness. In honeybees, the timing of brood rearing and nest emergence in late winter/early spring is critical as colonies need to grow fast after winter to prepare for reproduction. However, the effects of stress on these life-history events in late winter/early spring and the possible consequences are not well understood. Therefore, we tested whether (i) honeybee colonies shift timing of brood rearing and nest emergence as response to stressors, and (ii) if there is a consequent loss of social resilience, reflected in colony fitness (survival, growth and reproduction). We monitored stressed (high load of the parasitic mite
Varroa destructor
or nutrition restricted) colonies and presumably non-stressed colonies from the beginning of 2020 till spring of 2021. We found that honeybee colonies do not shift the timing of brood rearing and nest emergence in spring as a coping mechanism to stressors. However, we show that there is loss of social resilience in stressed colonies, leading to reduced growth and reproduction. Our study contributes to better understanding the effects of stressors on social resilience in eusocial organisms.
Robustness versus productivity during evolutionary community assembly: short-term synergies and long-term trade-offs
Authors: Lepori Vasco J. , Loeuille Nicolas , Rohr Rudolf P.
Published: January 2024

The realization that evolutionary feedbacks need to be considered to fully grasp ecological dynamics has sparked interest in the effect of evolution on community properties like coexistence and productivity. However, little is known about the evolution of community robustness and productivity along diversification processes in species-rich systems. We leverage the recent structural approach to coexistence together with adaptive dynamics to study such properties and their relationships in a general trait-based model of competition on a niche axis. We show that the effects of coevolution on coexistence are two-fold and contrasting depending on the time scale considered. In the short term, evolution of niche differentiation strengthens coexistence, while long-term diversification leads to niche packing and decreased robustness. Moreover, we find that coevolved communities tend to be on average more robust and more productive than non-evolutionary assemblages. We illustrate how our theoretical predictions echo in observed empirical patterns and the implications of our results for empiricists and applied ecologists. We suggest that some of our results such as the improved robustness of Evolutionarily Stable Communities could be tested experimentally in suitable model systems.
Human foot form and function: variable and versatile, yet sufficiently related to predict function from form
Authors: Schuster Robert W. , Cresswell Andrew G. , Kelly Luke A.
Published: January 2024

The human foot is a complex structure that plays an important role in our capacity for upright locomotion. Comparisons of our feet with those of our closest extinct and extant relatives have linked shape features (e.g. the longitudinal and transverse arches, heel size and toe length) to specific mechanical functions. However, foot shape varies widely across the human population, so it remains unclear if and how specific shape variants are related to locomotor mechanics. Here we constructed a statistical shape–function model (SFM) from 100 healthy participants to directly explore the relationship between the shape and function of our feet. We also examined if we could predict the joint motion and moments occurring within a person's foot during locomotion based purely on shape features. The SFM revealed that the longitudinal and transverse arches, relative foot proportions and toe shape along with their associated joint mechanics were most variable. However, each of these only accounted for small proportions of the overall variation in shape, deformation and joint mechanics, most likely owing to the high structural complexity of the foot. Nevertheless, a leave-one-out analysis showed that the SFM can accurately predict joint mechanics of a novel foot, based on its shape and deformation.
Is there a sicker sex? Dose relationships modify male–female differences in infection prevalence
Authors: Butterworth Nathan J. , Heffernan Lindsey , Hall Matthew D.
Published: January 2024

Throughout the animal kingdom, there are striking differences in the propensity of one sex or the other to become infected. However, precisely when we should expect males or females to be the sicker sex remains unclear. A major barrier to answering this question is that very few studies have considered how the susceptibility of males and females changes across the full range of pathogen doses encountered in nature. Without quantifying this ‘dose–susceptibility’ relationship, we have likely underestimated the scope for sex differences to arise. Here, we use the
Daphnia magnia
–
Pasteuria ramosa
system to reveal that sex differences in susceptibility are entirely dose-dependent, with pathogens having a higher probability of successfully establishing an infection in mature males at low doses, but mature females at high doses. The scope for male–female differences to emerge is therefore much greater than previously appreciated—extending to sex differences in the upper limits to infection success, per-propagule infectivity risks and density-dependent pathogen behaviour. Applying this expanded scope across the animal kingdom will help us understand when and why a sicker sex emerges, and the implications for diseases in nature—where sex ratios, age structure and pathogen densities vary drastically.
Metformin mitigates insulin signaling variations induced by COVID-19 vaccine boosters in type 2 diabetes
Authors: Zhai Lixiang , Zhuang Min , Wong Hoi Ki , Lin Chengyuan , Zhang Jialing , Bao Gengyu , Zhang Yijing , Xu Shujun , Luo Jingyuan , Yuan Shuofeng , Wong Hoi Leong Xavier , Bian Zhao-xiang
Published: January 2024

Diabetes is associated with an increased risk of Coronavirus disease 2019 (COVID-19) vulnerability and mortality. COVID-19 vaccines significantly reduce the risks of serious COVID-19 outcomes, but the impact of COVID-19 vaccines including their effectiveness and adverse effects in patients with diabetes are not well known yet. Here, we showed that 61.1% patients with type 2 diabetes, but not healthy controls, exhibited aggravated insulin resistance towards the booster shots of the COVID-19 vaccine. Furthermore, we showed that COVID-19 vaccination once a week also impaired insulin sensitivity in healthy mice after four weeks. We further showed that metformin, a common anti-diabetic medication, improved the impaired insulin signaling induced by COVID-19 vaccination in mice. This study suggests clinical implications for the close monitoring of glycemic control in diabetic patients after receiving COVID-19 vaccines and indicates the beneficial action of metformin in counteracting insulin signaling variations induced by COVID-19 vaccination in diabetic patients.
First-episode mild depression in young adults is a pre-proatherogenic condition even in the absence of subclinical metabolic syndrome: lowered lecithin-cholesterol acyltransferase as a key factor
Authors: Maes Michael , Vasupanrajit Asara , Jirakran Ketsupar , Zhou Bo , Tunvirachaisakul Chavit , Almulla Abbas F.
Published: January 2024

Background

Major depression is classified into distinct subtypes: simple (SDMD) and major dysmood disorder (MDMD). MDMD patients exhibit elevated atherogenicity and decreased reverse cholesterol transport (RCT). However, comprehensive data regarding lipid metabolism is absent in first episode (FE)-SDMD.

Objectives

In this case-control study, plasma lipid levels, lecithin-cholesterol acyltransferase (LCAT), free cholesterol, ApoA1, ApoB, and ApoE are compared between academic students with first episode SDMD (FE-SDMD) (n=44) or SDMD (n=64) and control students (n=44), after excluding those with metabolic syndrome (MetS).

Results

LCAT is decreased, and free cholesterol and ApoE increased in subjects with SDMD and FE-SDMD as compared with controls. There were no significant alterations in high-density lipoprotein cholesterol (HDLc), apolipoprotein (Apo)A1, RCT, ApoB and triglycerides in SDMD. LCAT, free cholesterol and atherogenicity indices are significantly associated with suicidal behaviors and the SDMD phenome. The effects of LCAT on those phenome features is completely mediated by free cholesterol and brooding. SDMD and FE-SDMD patients without signs of subclinical MetS show lowered LCAT and increased free cholesterol as compared with normal controls. There are significant interactions between the SDMD and FE-SDMD diagnosis and subclinical MetS, which result in decreased HDLc and RCT, and an increased ApoB/ApoA ratio.

Discussion

FE-SDMD and SDMD are pre-proatherogenic states, because of decreased LCAT, and increased free cholesterol and ApoE, and their intersections with subclinical MetS. These aberrations may drive atherogenicity, and activation of peripheral and central oxidative, neuro-immune, and degenerative pathways. Individuals with FE-SDMD should be screened for increased atherogenicity risk by measuring LCAT, free cholesterol and ApoE.
Disentangling the relationship between cancer mortality and COVID-19 in the US
Authors: Hansen Chelsea L. , Viboud Cécile , Simonsen Lone
Published: January 2024

Several countries have reported that deaths with a primary code of cancer did not rise during COVID-19 pandemic waves compared to baseline pre-pandemic levels. This is in apparent conflict with findings from cohort studies where cancer has been identified as a risk factor for COVID-19 mortality. Here we further elucidate the relationship between cancer mortality and COVID-19 on a population level in the US by testing the impact of death certificate coding changes during the pandemic and leveraging heterogeneity in pandemic intensity across US states. We computed excess mortality from weekly deaths during 2014-2020 nationally and for three states with distinct COVID-19 wave timing (NY, TX, and CA). We compared pandemic-related mortality patterns from underlying and multiple cause (MC) death data for six types of cancer and compared to that seen for chronic conditions such as diabetes and Alzheimer’s. Any death certificate coding changes should be eliminated by study of MC data.

Nationally in 2020, we found only modest excess MC cancer mortality (∼13,600 deaths), representing a 3% elevation over baseline level. Mortality elevation was measurably higher for less deadly cancers (breast, colorectal, and hematologic, 2-7%) than cancers with a poor 5-year survival (lung and pancreatic, 0-1%). In comparison, there was substantial elevation in MC deaths from diabetes (37%) and Alzheimer’s (19%). Homing in on the intense spring 2020 COVID-19 wave in NY, mortality elevation was 1-16% for different types of cancer and 128% and 49% for diabetes and Alzheimer’s, respectively. To investigate the peculiar absence of excess mortality on deadly cancers, we implemented a demographic model and simulated the expected covid-related mortality using COVID-19 attack rates, life expectancy, population size and mean age for each chronic condition. This model indicates that these factors largely explain the considerable differences in observed excess mortality between these chronic conditions during the COVID-19 pandemic, even if cancer had increased the relative risk of mortality by a factor of 2 or 5.

In conclusion, we found limited elevation in cancer mortality during COVID-19 waves, even after considering MC mortality, and this was especially pronounced for the deadliest cancers. Our demographic model predicted low expected excess mortality in populations living with certain types of cancer, even if cancer is a risk factor for COVID-19 fatality, due to competing mortality risk. We also find a moderate increase in excess mortality from hematological cancers, aligned with other types of observational studies. While our study concentrates on the immediate consequences of the COVID-19 pandemic on cancer mortality in 2020, further research should consider excess mortality in the complete pandemic period. Also, a study of the delayed impact of the pandemic on cancer mortality due to delayed diagnosis and treatment during the pandemic period is warranted.
Higher long-term visit-to-visit blood pressure variability is associated with severe cerebral small vessel disease in the general population
Authors: Zhao Xinyu , Ying Hui , Li Jing , Shi Xianquan , Chen Shuohua , Lv Han , Wu Shouling , Wang Zhenchang
Published: January 2024

Background

Long-term blood pressure (BP) variability is related to several diseases, but its impact on cerebral small vessel disease (cSVD) is uncertain. The study explored the relationship between BP variability, total cSVD burden, and its typical features.

Method

The study involved 1284 participants from the Kailuan cohort. From 2006 to 2022, systolic BP (SBP), diastolic BP (DBP), and pulse pressure (PP) variability were calculated as low, middle, or high. Magnetic resonance imaging was used to identify white matter hyperintensities (WMH), lacunae (LA), cerebral microbleeds (CMBs), and visible perivascular spaces (PVS). The burden of cSVD was defined as non, mild, moderate, or severe. Logistic regression was used to estimate the odds ratio (OR) and confidence interval (CI).

Results

High SBP variability was associated with moderate cSVD burden (OR=1.89, 95% CI: 1.09-3.29) and PVS (OR= 1.62, 95%CI: 1.10-2.39). The DBP was associated with LA (OR=1.74, 95%CI: 1.06-2.84). The PP showed obvious risk effects on moderate/severe cSVD burden (OR= 1.99, 95%CI: 1.17-3.41; OR=2.49, 1.34-4.63). These associations were modified by age and hypertension status. In the young adults (age<60 years old), only high PP variability associated with severe cSVD burden (OR=3.33, 95%CI: 1.31-8.44), LA (OR=3.02, 95%CI: 1.31-6.93), and PVS (OR=1.86, 95%CI: 1.20-2.88). The risk effect of SBP and PP variability on cSVD burden was only significant in the participants with hypertension.

Conclusion

High long-term BP variability, especially in combination with hypertension, is a risk factor for total cSVD burden, LA, and PVS. it is crucial to pay attention to PP variability in young adults.
Evaluation of the Effects of Oxidative Stress and Biomarkers of Inflammation in Cardiomyopathy Sufferers
Authors: Tiwari Shivam , Shankar Om , Singh Royana , Yadav Ajay Kumar , Maurya Anil Kumar , Choudhary Umesh
Published: January 2024

Introduction

Cardiovascular disease can develop and worsen as a result of inflammation and oxidative stress. The current research looked into the relationship between oxidative damage and biomarkers of inflammation in individuals with cardiomyopathy.

Methods

Particular kits for ELISA were used to measure the serum concentrations of CRP, TNF-α, IL-6, and NT-proBNP. These specific ELISA kits are based on sandwich enzyme immunoassay techniques whose results are quantitative. The accuracy of the tests was established by comparing them to control sera that were included in the kits and had known quantities of the analytes.

Results

When compared to individuals without cardiomyopathy (control group), we found that cardiomyopathy patients had significantly higher blood C-reactive protein concentrations (P =<0.0001). When compared between control case and cardiomyopathy patients, then find that cardiomyopathy patients had significantly higher concentrations of tumour necrosis factor-alpha (TNF-alpha) (P =<0.0001). TNF-α associated favourably with malondialdehyde (P =<0.0001, r =0.4524) and glutathione peroxidase (GPX) (P =<0.0001, r =0.8311) in Cardiomyopathy patients. Interleukin-6 was not significantly linked with GPX (P =0.0001, r =-0.1194) in cardiomyopathy patients. In those with cardiomyopathy, there was a strong association (P=<0.0001, r=0.4826) between malondialdehyde and NT-proBNP. Furthermore, we observed that the activity of glutathione peroxidase (GPX) exhibited a significant connection with NT-proBNP (P =<0.0001, r = 0.6084) in all cardiomyopathy patients.

Conclusions

In cardiomyopathy patients, but not in normal cases, there is a correlation between inflammatory and oxidative stress indicators. These findings imply intricate cross-talk between the two cellular processes in late-stage cardiomyopathy.
A Human Factors Approach to Childhood Pneumonia A qualitative study in Malawian primary care
Authors: Mbakaya Balwani , Chisale Master R.O. , Wu Tsung-Shu Joseph , Ledwidge Mark T , Nyambalo Billy , Watson Chris , Gallagher Joe
Published: January 2024

Introduction

Pneumonia is one of the major causes of childhood mortality worldwide. Most of these deaths are readily preventable or treatable with proven cost effective interventions. The aim of this study is to investigate the assessment and management of childhood pneumonia in primary care in Malawi.

Methods

Semi-structured interviews were used to elicit accounts of the assessment, treatment and referral process as experienced by staff and caregivers in 10 health facilities in Northern Malawi. Staff members dealing with assessment of children under-five years of age (Doctors, Clinical Officers, Medical Assistants, Nurses, Nurse Midwife Technicians, Student Nurses and Health Surveillance Assistants) were included. It also involved policy makers from the area and caregivers of children presenting with pneumonia. Data was analysed using thematic analysis following the SEIPS 101 tools (task sequence, use of technology and tools, and work system barriers and facilitators).

Results

43 interviews were undertaken. A process map of the flow of patients with pneumonia was created, showing the tasks undertaken and the interactions between staff and patients. In their interviews caregivers identified a number of barriers to appropriate care including insufficient education for caregivers on the management of sick children and distance to healthcare availability. Staff identified several organisational elements that served as barriers to the implementation of care. They included workload, lack of resources such as medications and batteries, uncertainty regarding markers of severity and need to give all antibiotics. The health passport system and effective teamwork and community were highlighted as being important facilitators.

Conclusion

This study provides information on the challenges and issues involved in managing childhood pneumonia in primary care in Malawi. These barriers included a lack of resources, staff and caregiver education and heavy workload. The ability to identify severe illness accurately and identify those who do not require antibiotics were highlighted as issues for health workers.
Gene dysregulation among virally suppressed people living with HIV links to non-AIDS defining cancer pathways
Authors: Quach Bryan C. , Earley Eric , Zhou Linran , Willis Caryn , Marks Jesse A. , Stratford Jeran K. , Fang Fang , Bierut Laura J. , Milloy M-J S. , Hayashi Kanna , DeBeck Kora , Hancock Dana B. , Xu Ke , Aouizerat Bradley E. , Johnson Eric O.
Published: January 2024

Combination antiretroviral therapy (ART) has changed the landscape of the HIV epidemic by providing an effective means for viral suppression to people living with HIV (PLWH). Understanding living with HIV as a chronic disease requires an improved understanding of how HIV and/or ART impacts susceptibility to and development of co-occurring conditions. Genome-wide gene expression (transcriptome) differences provide a key view into biological dysregulation associated with living with HIV. Here we present the first whole blood transcriptome-wide study comparing gene expression profiles between virally suppressed PLWH and HIV negative individuals (N=555). We identify 566 genes and 5 immune cell types with differential proportions by HIV status, which were significantly enriched for immune function and cancer pathways. Leveraging quantitative trait loci (QTL) for these HIV status-associated genes, partitioned heritability, and colocalization analyses, we observed limited genetic drivers of these relationships. Our findings suggest that gene dysregulation does not return to a pre-infection state for virally suppressed PLWH, and that persistent gene dysregulation is broadly associated with immune function and cancer pathways, highlighting potential biological drivers for these causes of excess mortality and targets for pharmacological preventative treatment among PLWH.
Neonatal Respiratory Morbidity among Late Preterm Births by Planned Mode of Delivery and Gestational Age
Authors: Clapp Mark A. , Li Siguo , Cohen Jessica L. , Gyamfi-Bannerman Cynthia , Knudsen Amy B. , Lorch Scott A , Thaweethai Tanayott , Wright Jason D. , Kaimal Anjali J. , Melamed Alexander
Published: January 2024

Objective

To estimate the effect of late preterm antenatal steroids on the absolute risk of respiratory morbidity among subgroups of patients based on the planned mode of delivery and gestational age at presentation.

Methods

This was a secondary analysis of the Antenatal Late Preterm Steroid (ALPS) Trial, a multicenter trial originally conducted within the NICHD’s MFMU network of individuals with singleton gestations and without pre-existing diabetes who were at high risk for late preterm delivery (34-36 weeks of gestation). We fit binomial regression models to estimate the absolute risk of respiratory morbidity, with and without steroid administration, by gestational age and planned mode of delivery at the time of presentation. We assumed a homogenous effect of steroids on the log-odds scale, as was reported in the ALPS trial. The primary outcome was neonatal respiratory morbidity, as defined in the ALPS Trial

Results

The analysis included 2,825 patients at risk for late preterm birth. The risk of respiratory morbidity varied significantly by planned mode of delivery (adjusted risk ratio (aRR) 1.90 (95% confidence interval (CI) 1.55, 2.33) for cesarean compared to vaginal delivery) and day of gestation at presentation (aRR 0.92 (95% CI 0.90, 0.94)). For those planning a cesarean delivery and presenting in the 34th week of gestation, the risk of neonatal respiratory morbidity was 39.4% (95% CI 30.8, 47.9%) without steroids and 32.0% (95% CI 24.6, 39.4%) with steroids. In contrast, for patients presenting in the 36th week and planning a vaginal delivery, the risk of neonatal respiratory morbidity was 6.9% (95% CI 5.6, 8.6%) without steroids and 5.6% (95% 4.2, 7.0%) with steroids.

Conclusion

The absolute risk of neonatal respiratory morbidity among patients at risk for late preterm delivery varies considerably by gestational age at presentation and planned mode of delivery. As only communicating the relative risk reduction of antenatal steroids for respiratory morbidity may lead to an inaccurate perception of benefit, individualized estimates of absolute risk expected with and without treatment may inform shared decision-making.
AI-powered Coronary Artery Calcium Scans (AI-CAC) Enables Prediction of Heart Failure and Outperforms NT-proBNP: The Multi-Ethnic Study of Atherosclerosis
Authors: Naghavi Morteza , Reeves Anthony , Budoff Matthew , Li Dong , Atlas Kyle , Zhang Chenyu , Atlas Thomas , Henschke Claudia , Defilippi Christopher , Levy Daniel , Yankelevitz David
Published: January 2024

Introduction

Coronary artery calcium (CAC) scans contain useful information beyond the Agatston CAC score that is not currently reported. We recently reported that artificial intelligence (AI)-enabled cardiac chambers volumetry in CAC scans (AI-CAC) predicted incident atrial fibrillation in the Multi-Ethnic Study of Atherosclerosis (MESA). In this study, we investigated the performance of AI-CAC for prediction of incident heart failure (HF) and compared it with 10 known clinical risk factors, NT-proBNP, and the Agatston CAC score.

Methods

We applied AI-CAC to 5750 CAC scans of asymptomatic individuals (ages 45-84, 52% women, White 40%, Black 26%, Hispanic 22% Chinese 12%) free of known cardiovascular disease at the MESA baseline examination (2000-2002). We then used the 15-year outcomes data and compared the C-statistic of AI-CAC with NT-proBNP and the Agatston score for predicting incident HF versus 10 known clinical risk factors (age, gender, body surface area, diabetes, current smoking, hypertension medication, systolic and diastolic blood pressure, LDL, HDL, total cholesterol, and hs-CRP).

Results

Over 15 years of follow-up, 256 HF events accrued. The ROC area under the curve for predicting HF with AI-CAC (0.826) was significantly higher than NT-proBNP (0.742) and Agatston score (0.712) (p<.0001), and comparable to clinical risk factors (0.818, p=0.4141). AI-CAC category-free NRI significantly improved on clinical risk factors (0.43), NT-proBNP (0.68), and Agatston score (0.71) for HF prediction at 15 years (p<0.0001).

Conclusion

AI-CAC significantly outperformed NT-proBNP and the Agatston CAC score and significantly improved category-free NRI of clinical risk factors for incident HF prediction.
Multi-omic network analysis identifies dysregulated neurobiological pathways in opioid addiction
Authors: Sullivan Kyle A. , Kainer David , Lane Matthew , Cashman Mikaela , Miller J. Izaak , Garvin Michael R. , Townsend Alice , Quach Bryan C. , Willis Caryn , Kruse Peter , Gaddis Nathan C. , Mathur Ravi , Corradin Olivia , Maher Brion S. , Scacheri Peter C. , Sanchez-Roige Sandra , Palmer Abraham A. , Troiani Vanessa , Chesler Elissa J. , Kember Rachel L. , Kranzler Henry R. , Justice Amy C. , Xu Ke , Aouizerat Bradley E. ,   VA Million Veteran Program, Hancock Dana B. , Johnson Eric O. , Jacobson Daniel A.
Published: January 2024

Opioid addiction constitutes a public health crisis in the United States and opioids cause the most drug overdose deaths in Americans. Yet, opioid addiction treatments have limited efficacy. To help address this problem, we used network-based machine learning techniques to integrate results from genome-wide association studies (GWAS) of opioid use disorder and problematic prescription opioid misuse with transcriptomic, proteomic, and epigenetic data from the dorsolateral prefrontal cortex (dlPFC) in opioid overdose victims. We identified 211 highly interrelated genes identified by GWAS or dysregulation in the dlPFC of individuals with opioid overdose victims that implicated the Akt, BDNF, and ERK pathways, identifying 414 drugs targeting 48 of these opioid addiction-associated genes. This included drugs used to treat other substance use disorders and antidepressant drugs. Our synthesis of multi-omics using a systems biology approach revealed key gene targets that could contribute to drug repurposing, genetics-informed addiction treatment, and future discovery.
Cognitive impairment is a risk factor for long-term outcomes in septic patients: A retrospective observational study
Authors: Koami Hiroyuki , Sakamoto Yuichiro , Furukawa Yutaro , Mouri Kosuke , Matsuoka Ayaka , Shinada Kota , Nakayama Kento , Iwanaga Sachiko , Narumi Shogo , Koba Mayuko
Published: January 2024

The importance of long-term outcomes after sepsis has been increasingly emphasized in recent years; however, little is known about the relationship between pre-sepsis patient characteristics and long-term outcomes. This study examined the impact of patient characteristics pre-admission, specifically physical, cognitive, and emotional disorders, on long-term clinical outcomes of sepsis. From August 2014 to July 2016, this study included adult patients admitted to our hospital with a diagnosis of sepsis who were followed up for one year. These 76 patients were classified as Survivors (n=31) or Deceased (n=45), based on their one-year outcomes. In this single-center, retrospective study, 59% of sepsis patients died within one year. Multiple logistic regression models employing significant parameters from univariate analysis revealed that cognitive impairment (CI) is an independent risk factor for 1-year outcome [OR 0.184, 95% CI 0.047-0.722, P=0.0152]. Furthermore, through another univariate analysis and a log-rank test between the CI group and the Control group, created by reclassifying the same 76 patients, CI was significantly associated with a lower 1- year survival rate (25.0% vs 50.0%, P=0.03, log-rank P=0.0332). The composite outcome of either death or being bedridden at the point of discharge was also significantly higher in the CI group than the Control group (100.0% vs 75.0%, P=0.0028). These results indicate that pre-septic CI is a reliable, independent predictor of poor long-term clinical outcomes for sepsis patients.