bluuebunny/crossref_metadata_2025 huggingface dataset:
The impact of an oral glucose load on IFN-γ-release in persons infected with Mycobacterium tuberculosis
Authors: Lorentsson Hans Johan Niklas , Clausen Christina Reinholdt , Faurholt-Jepsen Daniel , Hansen Katrine Bagge , Ritz Christian , Jensen Sidse Graff , Rasmussen Erik Michael , Jørgensen Anja , Lillebaek Troels , Knop Filip , Ravn Pernille
Published: September 2024

Background and objective

To diagnose tuberculosis infection (TBI), whole blood is incubated with M.tuberculosis (Mtb)-specific peptides and the release of interferon-γ (IFN-γ) is measured in IFN-γ-release assays (IGRAs). Hyperglycaemia and fluctuations in blood glucose may modulate IFN-γ-release. Here, we investigated if glucose intake affects IFN-γ-release or IGRA results in IGRAs taken during an oral glucose tolerance test (OGTT).

Methods

Persons with TB disease (TB) or TBI underwent a standard 75-g OGTT at the start and end of treatment for TB or TBI. Blood for the IGRA QuantiFERON-TB Gold Plus (QFT) containing Mtb-specific tubes (TB1 and TB2), a non-specific mitogen tube (MIT) and an empty control tube (NIL) was drawn at sample-timepoints -15 (baseline), 60, 90, 120 and 240 min during the OGTT. Blood glucose was measured in parallel at all timepoints. IFN-γ-release (after subtraction of NIL) at each timepoint was compared with baseline using linear-mixed-model analysis.

Results

Twenty-four OGTTs from 14 participants were included in the final analysis. Compared to baseline, IFN-γ-release was increased at sample-timepoint 240 min for TB1; geometric mean (95% confidence interval) 3.0 (1.5–6.2) vs 2.5 (1.4–4.4) IU/mL (p = 0.047), and MIT; 182.6 (103.3–322.9) vs 146.0 (84.0–254.1) IU/mL (p = 0.002). Plasma glucose levels were not associated with IFN-γ-release and the QFT test results were unaffected by the OGTT.

Conclusion

Ingestion of glucose after a 10-h fast was associated with increased IFN-γ-release after 240 min in the MIT tube. However, there was no association between plasma glucose levels at the QFT sampling timepoint and IFN-γ-release. Furthermore, the QFT test results were not affected by glucose intake. The overall effect of an OGTT and prevailing plasma glucose levels on IFN-γ-release in IGRAs seem limited.

Trial registration

Trial registration ID: NCT04830462 (https://clinicaltrials.gov/study/NCT04830462). Registration date: 05-Apr-2021.
Vitamin B12 responsive developmental and epileptic encephalopathy due to a novel mutation in the FUT2 gene: a case report
Authors: Bandara PKBUC , Wijenayake Wasana , Fernando Sanjaya , Padeniya Padmapani , Mettananda Sachith
Published: September 2024

Background

Vitamin B12 deficiency is a recognised cause of neurological manifestations, including peripheral neuropathy, behavioural changes, and seizures. However, developmental and epileptic encephalopathy due to vitamin B12 deficiency is very rare. Here, we report an infant with vitamin B12-responsive developmental and epileptic encephalopathy due to a novel mutation in the fucosyltransferase 2 (FUT2) gene responsible for vitamin B12 absorption.

Case presentation

An 11-month-old girl of non-consanguineous parents presented with recurrent episodes of seizures since four months. Her seizures started as flexor epileptic spasms occurring in clusters resembling infantile epileptic spasms syndrome with hypsarrhythmia in the electroencephalogram. She was treated with multiple drugs, including high-dose prednisolone, vigabatrin, sodium valproate, levetiracetam and clobazam, without any response, and she continued to have seizures at 11 months. She had an early developmental delay with maximally achieving partial head control and responsive smile at four months. Her development regressed with the onset of seizure; at 11 months, her developmental age was below six weeks. On examination, she was pale and had generalised hypotonia with normal muscle power and reflexes.

Her full blood count and blood picture revealed macrocytic anaemia with oval and round macrocytes. Bone marrow aspiration showed hypercellular marrow erythropoiesis with normoblastic and megaloblastic maturation. Due to the unusual association of refractory epilepsy and megaloblastic anaemia, a rare genetic disease of the vitamin B12 or folate pathways was suspected. The whole exome sequencing revealed a homozygous missense variant in exon 2 of the FUT2 gene associated with reduced vitamin B12 absorption and low plasma vitamin B12 levels, confirming the diagnosis of vitamin B12 deficiency related developmental and epileptic encephalopathy. She was started on intramuscular hydroxocobalamin, for which she showed a marked response with reduced seizure frequency.

Conclusion

We report a novel variant in the FUT2 gene associated with vitamin B12-responsive developmental and epileptic encephalopathy and megaloblastic anaemia. This case report highlights the importance of timely genetic testing in children with refractory developmental and epileptic encephalopathy to identify treatable causes.
Dissonance between posts of health agencies and public comments regarding COVID-19 and vaccination on Facebook in Northern California
Authors: Calabrese Christopher , Xue Haoning , Zhang Jingwen
Published: September 2024

Background

Public health crises, such as the COVID-19 pandemic, have prompted a need for health agencies to improve their disease preparedness strategies, informing their communities of new information and promoting preventive behaviors to help curb the spread of the virus.

Methods

We ran unsupervised machine learning and emotion analysis, validated with manual coding, on posts of health agencies (N = 1588) and their associated public comments (N = 7813) during a crucial initial period of the COVID-19 pandemic (January 2020 to February 2021) among nine different counties with a higher proportion of vaccine-hesitant communities in Northern California. In addition, we explored differences in concerns and expressed emotions by two key group-level factors, county-level COVID-19 death rate and political party affiliation.

Results

We consistently find that while health agencies primarily disseminated information about COVID-19 and the vaccine, they failed to address the concerns of their communities as expressed in public comment sections. Topics among public audiences focused on concerns with the COVID-19 vaccine safety and rollout, state mandates, flu vaccination, and frustration with politicians, and they expressed more positive and more negative emotions than health agencies. Further, there were several differences in primary topics and emotions expressed among public audiences by county-level COVID-19 death rate and political party affiliation.

Conclusion

While this research serves as a case study, findings indicate how local health agencies, and their audiences, discuss their perceptions and concerns regarding the COVID-19 pandemic and may inform health communication researchers and practitioners on how to prepare and manage for emerging health crises.
Cost minimisation analyses of birth care in low-risk women in Norway: a comparison between planned home birth and birth in a standard obstetric unit
Authors: Joranger Pål , Huitfeldt Anette Schaumburg , Bernitz Stine , Blix Ellen
Published: September 2024

Background

Evidence exists that planned home births for low-risk women in settings in which they have access to hospital transfer if needed are safe. The costs of planned home births, compared to low-risk births in obstetric units, are not clear. The aim of this study was to compare costs associated with hospital births versus home births under different home birth organizations.

Methods

We performed a cost minimisation analysis (CMA) based on decision-analytic modelling while assuming that health outcomes were not affected by place of birth. Estimations of resource use were mainly based on three existing Norwegian datasets: (1) women with planned home births (n = 354), (2) women with planned home births (n = 482) of which 63 were transferred to a hospital, and (3) women with planned births in a hospital (n = 1550).

Results

Planned home birth costs 45.9% (credibility interval [CrI] 39.1–54.2) of a low-risk birth at a hospital. For planned home birth, the birth was the costliest activity (32.1%). The costs for planned home birth were estimated to be €1872 (CrI 1694–2071) and included hospitalisations for some. Costs for only those with actual home birth was €1353 (CrI 1244–1469). Costs of a birth, including possible birth-related complications, in low-risk women in a hospital was €4077 (CrI 3575–4615).

When including the costs of being on call for one woman at a time, a planned home birth costs €5,531 (CrI 5,171–5,906), which is 135.7% (CrI 117.7–156.8) of low-risk births at a hospital. When organizing midwives in the on call teams for multiple women at a time, a planned home birth costs € 2,842 (CrI 2,647–3,053), which is 69.7% (CrI 60.3–80.9) of a low-risk birth in a hospital.

Conclusions

Home birth can be cost-effective if the midwives who facilitate home births are organised into larger groups, or they work for hospitals that also facilitate home births. A model in which midwives work separately or in pairs to assist with a home birth and are on call for one birth at a time may not be cost-effective.
OrgaMapper: a robust and easy-to-use workflow for analyzing organelle positioning
Authors: Schmied Christopher , Ebner Michael , Samsó Paula , Van Der Veen Rozemarijn , Haucke Volker , Lehmann Martin
Published: September 2024

Background

Eukaryotic cells are highly compartmentalized by a variety of organelles that carry out specific cellular processes. The position of these organelles within the cell is elaborately regulated and vital for their function. For instance, the position of lysosomes relative to the nucleus controls their degradative capacity and is altered in pathophysiological conditions. The molecular components orchestrating the precise localization of organelles remain incompletely understood. A confounding factor in these studies is the fact that organelle positioning is surprisingly non-trivial to address e.g., perturbations that affect the localization of organelles often lead to secondary phenotypes such as changes in cell or organelle size. These phenotypes could potentially mask effects or lead to the identification of false positive hits. To uncover and test potential molecular components at scale, accurate and easy-to-use analysis tools are required that allow robust measurements of organelle positioning.

Results

Here, we present an analysis workflow for the faithful, robust, and quantitative analysis of organelle positioning phenotypes. Our workflow consists of an easy-to-use Fiji plugin and an R Shiny App. These tools enable users without background in image or data analysis to (1) segment single cells and nuclei and to detect organelles, (2) to measure cell size and the distance between detected organelles and the nucleus, (3) to measure intensities in the organelle channel plus one additional channel, (4) to measure radial intensity profiles of organellar markers, and (5) to plot the results in informative graphs. Using simulated data and immunofluorescent images of cells in which the function of known factors for lysosome positioning has been perturbed, we show that the workflow is robust against common problems for the accurate assessment of organelle positioning such as changes of cell shape and size, organelle size and background.

Conclusions

OrgaMapper is a versatile, robust, and easy-to-use automated image analysis workflow that can be utilized in microscopy-based hypothesis testing and screens. It effectively allows for the mapping of the intracellular space and enables the discovery of novel regulators of organelle positioning.
National implementation trial of BeUpstanding™: an online initiative for workers to sit less and move more
Authors: Healy Genevieve N. , Goode Ana D. , Ulyate Lisa , Abbott Alison , Dunstan David W. , Eakin Elizabeth G. , Gilson Nicholas D. , Gunning Lynn , Jetann Jodie , LaMontagne Anthony D. , Moodie Marj , Mulcahy Samantha , Owen Neville , Shilton Trevor , Sweeny Leanne , Straker Leon , Winkler Elisabeth A. H.
Published: September 2024

Background

The online BeUpstanding™ program is an eight-week workplace-delivered intervention for desk-based workers to raise awareness of the benefits of sitting less and moving more and build a supportive culture for change. A workplace representative (the “champion”) delivers the program, which includes a workshop where teams collectively choose their sit less/move more strategies. A toolkit provides the champion with a step-by-step guide and associated resources to support program uptake, delivery, and evaluation. Here we report on the main findings from the Australian national implementation trial of BeUpstanding.

Methods

Recruitment (12/06/2019 to 30/09/2021) was supported by five policy and practice partners, with desk-based work teams from across Australia targeted. Effectiveness was measured via a single arm, repeated-measures trial. Data were collected via online surveys, toolkit analytics, and telephone calls with champions. The RE-AIM framework guided evaluation, with adoption/reach (number and characteristics); effectiveness (primary: self-reported workplace sitting time); implementation (completion of core components; costs); and, maintenance intentions reported here. Linear mixed models, correcting for cluster, were used for effectiveness, with reach, adoption, implementation, and maintenance outcomes described.

Results

Of the 1640 website users who signed-up to BeUpstanding during the recruitment period, 233 were eligible, 198 (85%) provided preliminary consent, and 118 (50.6%) champions consented and started the trial, with 94% (n = 111 champions) completing. Trial participation was from across Australia and across industries, and reached 2,761 staff, with 2,248 participating in the staff survey(s): 65% female; 64% university educated; 17% from a non-English speaking background. The program effectively changed workplace sitting (-38.5 [95%CI -46.0 to -28.7] minutes/8-hour workday) and all outcomes targeted by BeUpstanding (behaviours and culture), with small-to-moderate statistically-significant effects observed. All participating teams (n = 94) completed at least 5/7 core steps; 72.4% completed all seven. Most champions spent $0 (72%) or >$0-$5 (10%) per team member; most (67/70 96%) intended to continue or repeat the program.

Conclusions

BeUpstanding can be adopted and successfully implemented by a range of workplaces, reach a diversity of staff, and be effective at creating a supportive culture for teams of desk-based workers to sit less and move more. Learnings will inform optimisation of the program for longer-term sustainability.

Trial registration

ACTRN12617000682347.
Frequency and genotyping of group A rotavirus among Egyptian children with acute gastroenteritis: a hospital-based cross-sectional study
Authors: Azzazy Ensaf A. , Amer Rania M. , Abdellatif Ghada Mohammed , Abd-Elmoneim Hala Adel , Abo-Alella Doaa Alhussein
Published: September 2024

Background

This hospital-based cross-sectional study aims to investigate the epidemiologic and clinical characteristics of rotavirus group A (RVA) infection among children with acute gastroenteritis and to detect the most common G and P genotypes in Egypt.

Methods

A total of 92 stool samples were collected from children under five who were diagnosed with acute gastroenteritis. RVA in stool samples was identified using ELISA and nested RT-PCR. Common G and P genotypes were identified utilizing multiplex nested RT-PCR assays.

Results

RVA was detected at a rate of 24% (22 /92) using ELISA and 26.1% (24 /92) using VP6 nested RT-PCR. The ELISA test demonstrated diagnostic sensitivity, specificity, and accuracy of 91.7%, 100%, and 97.8%, respectively. G3 was the most prevalent G type (37.5%), followed by G1 (12.5%), whereas the most commonly detected P type were P[8] (41.7%) and P[6] (8.2%). RVA-positive samples were significantly associated with younger aged children (p = 0.026), and bottle-fed (p = 0.033) children. In addition, RVA-positive samples were more common during cooler seasons (p = 0.0001). Children with rotaviral gastroenteritis had significantly more frequent episodes of diarrhea (10.87 ± 3.63 times/day) and vomiting (8.79 ± 3.57 times/day) per day (p = 0.013 and p = 0.011, respectively). Moreover, they had a more severe Vesikari clinical score (p = 0.049).

Conclusion

RVA is a prevalent cause of acute gastroenteritis among Egyptian children in our locality. The discovery of various RVA genotypes in the local population, as well as the identification of common G and P untypeable strains, highlights the significance of implementing the rotavirus vaccine in Egyptian national immunization programs accompanied by continuous monitoring of strains.
Role of the biological active components of human milk on long-term growth and neurodevelopmental outcome
Authors: Peila Chiara , Riboldi Lorenzo , Coscia Alessandra
Published: September 2024

Human Milk is the best option for infant feeding; and for this reason, it should be promoted, protected, and supported. HM is an individual-specific-dynamic biofluid, characterized by an extreme variability in its composition. A wealth of literature has investigated how HM is related to healthy development. An association between HM composition, including nutrients and growth-related hormones as well as other bioactive components, and short-term and long-term infant outcomes could support this statement; however, the evidence is limited. In fact, HM composition is difficult to examine as it is dynamic and changes within a single feed, diurnally, according to stage of lactation and between and within populations. The aim of this review is summarizing only the innovative knowledge on the association between HM composition and long-term outcomes: infant growth and neurodevelopment. In this specific contest, macronutrients and historical biological component with well recognized effect were excluded (i.e. LCPUFA, DHA, iodine). Revised articles have been found in MEDLINE using breast milk-related outcomes, neurodevelopment, infant growth, breast milk-related biological factors, biomarkers, biological active components, and constituents as keywords. Moreover, we focus our search on the latest research results.
Use of virus-like particles and nanoparticle-based vaccines for combating picornavirus infections
Authors: Ren Mei , Abdullah Sahibzada Waheed , Pei Chenchen , Guo Huichen , Sun Shiqi
Published: September 2024

Picornaviridae are non-enveloped ssRNA viruses that cause diseases such as poliomyelitis, hand-foot-and-mouth disease (HFMD), hepatitis A, encephalitis, myocarditis, and foot-and-mouth disease (FMD). Virus-like particles (VLPs) vaccines mainly comprise particles formed through the self-assembly of viral capsid proteins (for enveloped viruses, envelope proteins are also an option). They do not contain the viral genome. On the other hand, the nanoparticles vaccine (NPs) is mainly composed of self-assembling biological proteins or nanomaterials, with viral antigens displayed on the surface. The presentation of viral antigens on these particles in a repetitive array can elicit a strong immune response in animals. VLPs and NPs can be powerful platforms for multivalent antigen presentation. This review summarises the development of virus-like particle vaccines (VLPs) and nanoparticle vaccines (NPs) against picornaviruses. By detailing the progress made in the fight against various picornaviruses such as poliovirus (PV), foot-and-mouth disease virus (FMDV), enterovirus (EV), Senecavirus A (SVA), and encephalomyocarditis virus (EMCV), we in turn highlight the significant strides made in vaccine technology. These advancements include diverse construction methods, expression systems, elicited immune responses, and the use of various adjuvants. We see promising prospects for the continued development and optimisation of VLPs and NPs vaccines. Future research should focus on enhancing these vaccines' immunogenicity, stability, and delivery methods. Moreover, expanding our understanding of the interplay between these vaccines and the immune system will be crucial. We hope these insights will inspire and guide fellow researchers in the ongoing quest to combat picornavirus infections more effectively.
Therapeutic targets of armored chimeric antigen receptor T cells navigating the tumor microenvironment
Authors: Li Xianjun , Chen Tianjun , Li Xuehan , Zhang Hanyu , Li Yingjing , Zhang Shuyuan , Luo Shengnan , Zheng Tongsen
Published: September 2024

Chimeric antigen receptor (CAR) T cell therapy, which targets tumors with high specificity through the recognition of particular antigens, has emerged as one of the most rapidly advancing modalities in immunotherapy, demonstrating substantial success against hematological malignancies. However, previous generations of CAR-T cell therapy encountered numerous challenges in treating solid tumors, such as the lack of suitable targets, high immunosuppression, suboptimal persistence, and insufficient infiltration owing to the complexities of the tumor microenvironment, all of which limited their efficacy. In this review, we focus on the current therapeutic targets of fourth-generation CAR-T cells, also known as armored CAR-T cells, and explore the mechanisms by which these engineered cells navigate the tumor microenvironment by targeting its various components. Enhancing CAR-T cells with these therapeutic targets holds promise for improving their effectiveness against solid tumors, thus achieving substantial clinical value and advancing the field of CAR-T cell therapy. Additionally, we discuss potential strategies to overcome existing challenges and highlight novel targets that could further enhance the efficacy of CAR-T cell therapy in treating solid tumors.
Rodents of Bahir Dar Blue Nile River Millennium Park, Ethiopia
Authors: Ejigu Dessalegn , Gelaw Marye
Published: September 2024

Background

Rodents are mammals of the order Rodentia, which are found in all continents except Antarctica. They are the most diverse groups of mammals representing 41% of all mammals and they are known with 33 families, 481 genera, and about 2277 species. The present study was conducted from December 2018 to August 2019 both during the dry and wet seasons using Sherman traps and live traps. Four trap sites namely forest, bushland, grassland, and sugarcane plantation were selected for data collection. Shannon-Wiener diversity index (H’) was used to compute rodent species diversity, Simpson’s index (D) to assess the number and abundance of rodents in the different habitats, and one-way ANOVA and independent samples t-test were used for data analysis.

Results

A total of 163 individual rodents were captured in 1776 trap nights of which 125 individuals were captured using live traps in 1176 trap nights and 38 individuals using snap traps in 600 trap nights. Among the total individual rodents captured in the Bahir Dar Blue Nile River Millennium Park, 63.8% (n = 104) were males and 36.2% (n = 59) were females. Males outnumbered females in all the grids and the difference was significant (t = 31.5, df = 10, p < 0.05). The relative abundance of rodent species indicated that 42.4% (n = 53) were Arvicanthis niloticus, 26.4% (n = 33) Rattus rattus, 17.6% (n = 22) Mus musculus, 8% (n = 10) Mastomys natalensis, and 5.6% (n = 7) Arvicanthis abyssinicus. There are more individual specimens of A. niloticus than other species identified in the area (F = 698.22, df = 4, p < 0.05). Distribution of rodents varied among the different habitats. As a result, the bushland habitat showed more diversity of rodents (H = 0.98) and comprised relatively the highest (51.2%, n = 64) number of individuals captured, while the forest habitat supported the lowest number of rodents (4%, n = 5), and the difference showed a significant difference (F = 873.37, df = 3, p < 0.05). Population density with 95% confident interval estimated as 166 individuals/ha (95% CI:164.43–167.57).

Conclusion

The present study provides basic information about population dynamics of rodents and contributes to design conservation strategies for rodents in particular and other biota of the area in general.
When do contemporary wildfires restore forest structures in the Sierra Nevada?
Authors: Chamberlain Caden P. , Bartl-Geller Bryce N. , Cansler C. Alina , North Malcolm P. , Meyer Marc D. , van Wagtendonk Liz , Redford Hannah E. , Kane Van R.
Published: September 2024

Background

Following a century of fire suppression in western North America, managers use forest restoration treatments to reduce fuel loads and reintroduce key processes like fire. However, annual area burned by wildfire frequently outpaces the application of restoration treatments. As this trend continues under climate change, it is essential that we understand the effects of contemporary wildfires on forest ecosystems and the extent to which post-fire structures are meeting common forest restoration objectives. In this study, we used airborne lidar to evaluate fire effects across yellow pine and mixed conifer (YPMC) forests of California’s Sierra Nevada. We quantified the degree to which forest structures in first-entry burned areas (previously unburned since ~ 1900s) and unburned controls aligned with restoration targets derived from contemporary reference sites. We also identified environmental conditions that contributed to more restorative fire effects.

Results

Relative to unburned controls, structural patterns in first-entry burned areas aligned more closely with reference sites. Yet, across all burn severities, first-entry wildfires were only moderately successful at meeting targets for canopy cover (48% total area) and ladder fuels (54% total area), and achieving these targets while also producing tree clump and opening patterns aligning with reference sites was less common (16% total area). Moderate-severity patches had the highest proportion of restorative fire effects (55–64% total area), while low- and high-severity patches were either too dense or too open, respectively. Our models (and publicly-available mapped predictions) indicated a higher probability of restorative effects within 1 km of previous fires, within the mid-upper climate range of the YPMC zone, and under moderate fire intensities (~ 1–2 m flame lengths).

Conclusions

First-entry wildfires can sometimes restore structural conditions by reducing canopy cover and ladder fuels and increasing structural heterogeneity, especially within moderate-severity patches. However, these initial fires represent just one step toward restoring dry forest ecosystems. Post-fire landscapes will require additional low- to moderate-intensity fires and/or strategic management interventions to fully restore structural conditions. In yet unburned forests, managers could prioritize mechanical treatments at lower elevations, early-season burning at mid to high elevations, and resource objective wildfires in landscapes with mosaics of past wildfires.
Effects of fire and fire-induced changes in soil properties on post-burn soil respiration
Authors: Johnson Dana B. , Yedinak Kara M. , Sulman Benjamin N. , Berry Timothy D. , Kruger Kelsey , Whitman Thea
Published: September 2024

Background

Boreal forests cover vast areas of land in the northern hemisphere and store large amounts of carbon (C) both aboveground and belowground. Wildfires, which are a primary ecosystem disturbance of boreal forests, affect soil C via combustion and transformation of organic matter during the fire itself and via changes in plant growth and microbial activity post-fire. Wildfire regimes in many areas of the boreal forests of North America are shifting towards more frequent and severe fires driven by changing climate. As wildfire regimes shift and the effects of fire on belowground microbial community composition are becoming clearer, there is a need to link fire-induced changes in soil properties to changes in microbial functions, such as respiration, in order to better predict the impact of future fires on C cycling.

Results

We used laboratory burns to simulate boreal crown fires on both organic-rich and sandy soil cores collected from Wood Buffalo National Park, Alberta, Canada, to measure the effects of burning on soil properties including pH, total C, and total nitrogen (N). We used 70-day soil incubations and two-pool exponential decay models to characterize the impacts of burning and its resulting changes in soil properties on soil respiration. Laboratory burns successfully captured a range of soil temperatures that were realistic for natural wildfire events. We found that burning increased pH and caused small decreases in C:N in organic soil. Overall, respiration per gram total (post-burn) C in burned soil cores was 16% lower than in corresponding unburned control cores, indicating that soil C lost during a burn may be partially offset by burn-induced decreases in respiration rates. Simultaneously, burning altered how remaining C cycled, causing an increase in the proportion of C represented in the modeled slow-cycling vs. fast-cycling C pool as well as an increase in fast-cycling C decomposition rates.

Conclusions

Together, our findings imply that C storage in boreal forests following wildfires will be driven by the combination of C losses during the fire itself as well as fire-induced changes to the soil C pool that modulate post-fire respiration rates. Moving forward, we will pair these results with soil microbial community data to understand how fire-induced changes in microbial community composition may influence respiration.
Current advances in CRISPR-Cas-mediated gene editing and regulation in cyanobacteria
Authors: Dong Zhengxin , Chen Lei , Wang Yu , Sun Tao , Zhang Weiwen
Published: September 2024

Photosynthetic cyanobacteria are important microbial models in basic research such as photosynthesis, biological rhythm, and the geochemical cycle of elements. Meanwhile, they attract significant attention to serve as "autotrophic cell factories", enabling the production of dozens of chemicals. In this case, genetic toolboxes especially gene editing and regulation tools with high efficiency are the basis of the development of related studies. Among them, clustered regularly interspaced palindromic repeats (CRISPR)-Cas related technologies have realized rapid and efficient gene editing, gene silence and activation in multiple organisms like Escherichia coli, budding yeast, plant and mammalian cells. To promote their understandings and applications in cyanobacteria, in this review, advances in CRISPR-Cas-mediated gene editing and regulations were critically discussed. Firstly, the elucidation of native CRISPR-Cas in cyanobacteria were concluded, which provided new tool candidates for further optimization. Secondly, basic principles and applications of CRISPR-Cas related gene editing and regulation tools used in cyanobacteria were respectively discussed. In the future, further studies on development of native CRISPR-Cas tools, continuous editing and dynamic regulation would significantly promote the synthetic biology researches in cyanobacteria.
Impact of Medicaid expansion on receipt of pancreatectomy in early-stage pancreatic cancer.
Authors: Gaddipati Greeshma Nihitha , Mensah Boniface , Atarere Joseph , Vasireddy Ramya , Bilalaga Mariah Malak , Akhiwu Ted , Singh Simardeep , Singh Tanmay , Kancharla Pragnan
Published: September 2024

106

Background:
Pancreatic cancer is estimated to rank third in cancer-related mortality in 2024 by the American Cancer Society. Despite the proven increase in 5-year survival with pancreatectomy in Early Pancreatic Cancer (EPC), it is nationally underutilized. Medicaid expansion (ME) under the Affordable Care Act is associated with gains in insurance coverage and early cancer diagnosis in patients with pancreatic cancer. However, its impact on the receipt of pancreatectomy in EPC remains unclear. In this study, we looked at the impact of ME on the uptake of pancreatectomy in EPC.
Methods:
We performed a retrospective observational study using the Surveillance, Epidemiology, and End Results (SEER) database, which included patients diagnosed with EPC (Stage 1 and Stage 2) between 2006 and 2021. Multivariate logistic regression was performed to ascertain the effects of ME on the uptake of pancreatectomy in patients with EPC in states that expanded vs. states that did not, with 2014 as an inflection point for policy implementation.
Results:
During this study period, 29,384 were diagnosed with EPC, 10,777 patients were diagnosed pre-ME and 18,607 post-ME. The odds of receipt of pancreatectomy for EPC in non-expansion states after 2014 was 20% higher than before 2014. However, this was not statistically significant [AOR – 1.20 (0.98-1.48)]. There was also no significant difference between the odds of receipt of treatment for EPC for ME states before [AOR- 1.27 (1.06-1.51)] and after [AOR-1.21 (1.01-1.44)] 2014. Increasing age, male sex, Black and Hispanic race, having an income lower than $65,000, and living in less populated areas were all associated with lower odds of receipt of pancreatectomy in EPC.
Conclusions:
ME was not associated with increased uptake of pancreatectomy in EPC. However, prior studies have shown that ME is linked to an earlier stage at pancreatic cancer diagnosis. This suggests that despite earlier diagnosis, other barriers to receiving treatment exist. Future studies are warranted to identify the limitations of policy change to improve outcomes of such aggressive cancer.

Logistic regression for receipt of pancreatectomy in early-stage pancreatic cancer.

Receipt of Surgical Treatment for Early Pancreatic cancer
Adjusted Odds Ratio (95% Confidence Interval)

Non- ME States (Pre-Expansion)
1.00 (Reference)

Non- ME States (Post -Expansion)
1.20 (0.98-1.48)

ME States (Pre-Expansion)
1.27 (1.06-1.51)

ME States (Post-Expansion)
1.21 (1.01-1.44)

ME- Medicaid expansion.
The impact of neighborhood socioeconomic deprivation on clinical outcomes for locally advanced and metastatic hepatocellular carcinoma: An incidence-based retrospective cohort study.
Authors: Shah Shreya , Raghu Apurva , Permuth Jennifer B , Chen Dung-Tsa , Park Margaret , Knott Cheryl , Powers Benjamin Daniel
Published: September 2024

108

Background:
Prior studies show that socioeconomic status impacts hepatocellular carcinoma (HCC) outcomes. However, these have used larger geographic areas such as zip codes or counties for assessment. Using a statewide cancer registry the Area Deprivation Index (ADI), a granular measure of socioeconomic deprivation (SED), was used to assess receipt of treatment and overall survival (OS) for locally advanced and metastatic HCC.
Methods:
The incidence-based Florida Cancer Data System was used to identify stage III/IV HCC patients diagnosed from 2007-2015. The ADI was used to measure SED and is a validated dataset that ranks neighborhoods (census block groups) from 1-100 (higher scores = higher deprivation) based on income, education, housing, and other socioeconomic factors. Demographic, tumor, and treatment variables were assessed using descriptive statistics, regression plots, and survival analysis. Chemotherapeutic treatment (CT) included receipt of chemotherapy and/or chemoembolization.
Results:
The study identified 2,534 eligible patients. Males comprised 80.6% of the cohort. The median age was 63 years. By SED quartile, there were significant differences by age, race, insurance, and receipt of chemotherapy (p<0.05) but no difference by gender, ethnicity, stage, or survival. Overall, 39.1% received chemotherapeutic treatment. However, 41.0% of the lowest-deprivation patients received CT compared to 32.1% in the highest-deprivation cohort (p<0.01). After adjustment for potential confounders, the lowest deprivation quartile had increased odds of CT compared to the highest deprivation quartile (OR 1.47; 95% CI,1.15-1.87). The median OS for the cohort was 4.0 months and was 4.6 and 3.3 months, respectively, for the lowest and highest deprivation quartiles (p<0.01). For patients who received and did not receive CT, the median OS was 8.0 and 2.2 months, respectively (p<0.01). However, there was no difference in median OS by SED for those who received CT (p=0.14).
Conclusions:
In an incidence-based, statewide cancer registry, the median OS for locally advanced and metastatic HCC remains poor and most patients do not receive CT. While there were differences in receipt of CT by SED, when patients did receive CT, median OS was similar across SED quartiles. These data suggest that SED may impact receipt of treatment and efforts are needed to understand and address treatment disparities.

Lowest Deprivation
Low Deprivation
High Deprivation
Highest Deprivation
p-Value

N=624

N=650

N=589

N=629

Chemotherapeutic treatment

0.001

No
347 (55.6%)
345 (53.1%)
339 (57.6%)
411 (65.3%)

Yes
256 (41.0%)
283 (43.5%)
235 (39.9%)
202 (32.1%)

Unknown
21 (3.4%)
22 (3.4%)
15 (2.5%)
15 (2.6%)

Vital Status

0.93

Alive
41 (5.7%)
44 (5.9%)
43 (6.0%)
44 (6.5%)

Dead
682 (94.3%)
695 (94.1%)
673 (94.0%)
632 (93.5%)
Influence of a community practice innovation on a statewide cancer drug repository network.
Authors: Sias Katie , Cloud Aimee , Melgarejo Kimberly , Norman Siobhan , Wietzke Julie , Schwartz Ashley , Seid Jerome E. , Jalloul Farah , Mackler Emily R.
Published: September 2024

115

Background:
Cancer drug repositories (CDRs) have the potential to minimize cancer medication waste while improving medication access to patients in need. Despite multiple states having legislation allowing for CDR programs, implementation remains suboptimal. The first CDRs to launch in Michigan were a fortuitous result of the support provided in embedding clinical pharmacists into community oncology practices via the Pharmacists Optimizing Oncology Care Excellence in Michigan, POEM, program. We describe these grassroot efforts as well as barriers to sustainability, ultimately resulting in formation of a statewide CDR Network, YesRx.
Methods:
This qualitative analysis of barriers and facilitators was conducted from interviews with Michigan’s first CDRs. Virtual group meetings were conducted monthly for 6-months from January 2023 – June 2023. Meetings were led by the coordinating center team of POEM. Workgroup attendees included POEM pharmacists who established the first 3 CDR programs in the State, a medical oncologist and longstanding advocate of CDRs, and a patient representative. Brainstorming sessions included open ended questions on experiences to date, benefits of CDR programs, barriers to growth, limitations in current CDR models, and beneficial areas for support. Interview findings were categorized as barriers or facilitators of site-specific implementation and recommendations for CDR model optimization.
Results:
All 3 CDRs reported positive outcomes from initiating the CDRs related to patient benefit and physician satisfaction. Items reported as challenges/barriers in the sustainability of individual site-managed CDRs: space (inventory growth exceeded designated storage capacity), complexity of inventory tracking, resources (staff and financial), inability to search state-wide for available inventory, inability to easily transfer medications between CDR sites (due to cost, documentation, and staff), inability to ship medications directly to a patient’s home, inability to serve cancer patients across the State who may be in need of medication or interested in donating. The top recommendations for CDR model optimization formed by this workgroup were a centralized, shared database of CDR inventory across the State, support for CDR medication transfers, and additional resource and storage capabilities. YesRx, a nonprofit service organization, was founded in July 2023 in collaboration with the first 3 CDRs to address the experienced barriers resulting in exponential state-wide access.
Conclusions:
Grassroot efforts of community-based clinical oncology pharmacists resulted in the first CDR programs in Michigan and their experiences guided the launch of a statewide network of CDRs created to expand cancer medication access for vulnerable and underserved people and communities.
Understanding the impact of historical redlining on prostate cancer care quality and treatment patterns and the association with modern metrics of disparity.
Authors: Zebib Laura , Herrel Lindsey A. , Dunn Rodney , Sekar Rishi
Published: September 2024

118

Background:
Sociodemographic and racial disparities persist in prostate cancer care, including associations between place-based indices and prostate cancer care quality and treatment modality. This study examines the impact of historical redlining conducted by the Home Owner’s Loan Corporation (HOLC) in 1933 on modern prostate cancer care quality.
Methods:
We performed a retrospective, observational cohort study utilizing Medicare claims data (2015-2019) of patients aged 66 or older with localized prostate cancer. ArcGIS was used to overlay HOLC grading to modern five-digit zip-codes and generate a weighted average HOLC grade for each zip. Data was then merged with modern metrics of social determinants of health including social vulnerability index (SVI) and dual eligibility. In order to assess historical and modern metrics of structural racism, patients across HOLC grade were compared to determine treatment modality and access to prostate cancer care quality. HOLC grade was then compared to SVI and dual eligibility in determining disparities.
Results:
We identified 14,630 patients with newly diagnosed prostate cancer who reside within an area that received a HOLC grade, of whom 10187 (70%) were white, 2910 (20%) were Black, and 1473 (10%) were another race or ethnicity. Patients in HOLC-graded areas were more likely to be socioeconomically disadvantaged (dual eligibility status, 11% vs. 4.1%, p<0.001; 4
th
Quartile SVI; 36% vs. 24%, p<0.001) and urban residents (99.9% vs 76%, p<0.001). Multivariable logistic regression analysis of patients who resided in HOLC-graded areas indicated that those in areas with worse HOLC-grade (per 1-grade difference) had lower odds of undergoing surgery (OR 0.89, CI 0.83-0.96, p=0.003), being treated by a high-volume practitioner (OR 0.86 CI 0.81-0.92, p<0.001), or undergoing pre-biopsy MRI (OR 0.94, CI 0.89-1.0, p=0.050), but similar odds of being seen by both a radiation oncologist and urologist (OR 1.03, CI 0.96-1.11, p=0.5). No significant interactions between HOLC grade and social vulnerability were found.
Conclusions:
This study reveals the enduring impact of historical redlining on prostate cancer care disparities, emphasizing the need for targeted interventions and housing policy reforms to promote equitable access to care. Racially explicit policies continue to shape healthcare disparities, independent of contemporary socioeconomic factors.
Adaptation of a modified Elixhauser comorbidity index to isolate the impact of body mass index on survival outcomes in patients with cancer in a large integrated healthcare system.
Authors: Newman Matthew T. , Zhuang Zimin , Cooper Robert Michael
Published: September 2024

124

Background:
Variable impacts of body mass index (BMI) on overall survival (OS) and cancer-specific survival (CSS) have been described in patients with cancer, with existing data highlighting both detrimental effects and malignancy-specific benefits. Real-world data derived from integrated healthcare systems are underexplored in this context, and tight control of confounding using validated tools such as the Elixhauser Comorbidity Index (ECI) is rarely employed in pre-existing studies. Herein, we offer a highly refined description of the impact of BMI on cancer-specific outcomes in a large patient cohort using a targeted ECI model.
Methods:
153,270 patient records were abstracted from an integrated healthcare system from 2010-2018, including descriptors of age, race/ethnicity, income, disease stage, and treatment regimens. Standardized derivation of BMI within one year prior to diagnosis was performed and categorized by World Health Organization definitions. A custom ECI was designed to exclude ICD codes for obesity to effectively isolate the impact of BMI on downstream analyses. Kaplan-Meier survival estimates of OS and CSS were constructed, and univariate and multivariate Cox proportional hazard (PH) modeling was performed to determine hazard ratios (HR).
Results:
When normalized to healthy BMI in multivariate modeling, we found a favorable dose-dependent relationship of overweight and obese BMI on OS and CSS independent of age, race/ethnicity, income, modified ECI score, cancer stage, or therapeutic regimen (Table). This advantage to OS and CSS was not as strongly reflected in severely obese patients, though still significant compared to healthy BMI counterparts. Being underweight was a negative prognostic indicator for OS and CSS in all patients compared to a healthy BMI.
Conclusions:
We demonstrate a beneficial impact of increased BMI on OS and CSS in a large cohort of patients treated in an integrated healthcare model independent of tightly controlled confounding. Specifically, we highlight the utility of isolating obesity using a targeted ECI model for comorbidity adjustment, which may provide a more robust measure of the influence of BMI on survival. Our findings raise questions regarding attention to adequate control of confounding in prior studies, as well as the potential benefit of removing variation in healthcare delivery in understanding these outcomes.

Adjusted HR of OS and CSS stratified by BMI category (*95% Confidence Interval).

BMI Category
Adjusted OS
Adjusted CSS

Normal Weight(18.5 – 24.9)
1 (reference)
1 (reference)

Underweight(< 18.5)
1.35 (1.25 – 1.45*)
1.28 (1.15 – 1.41)

Overweight(25 – 29.9)
0.83 (0.81 – 0.85)
0.84 (0.81 – 0.87)

Obese(30 – 39.9)
0.81 (0.79 – 0.83)
0.81 (0.78 – 0.84)

Severe Obesity(≥ 40)
0.86 (0.82 – 0.90)
0.82 (0.77 – 0.87)

Unknown
1.33 (1.24 – 1.43)
1.19 (1.07 – 1.31)