bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treating the invisible: Subclinical actinic keratosis detected by imiquimod
Authors: Kopera Daisy , Torrano Joachim , Soyer H. Peter 
Published: August 2023

AbstractBackgroundSkin in UV‐exposed areas may develop UV‐induced actinic damage in DNA sequences leading to proliferation of keratinocyte carcinoma, a type of non‐melanoma skin cancer. Actinic keratosis (AK) represents early‐stage in situ squamous cell carcinoma. It develops from the basal cell layer and may be present in subclinical stages, being reported as field cancerization, even before being clinically visible. Thus, we hypothesise that from the age of 50 + UV‐exposed skin features subclinical forms of AKs without visible skin lesions.ObjectivesThis study aims at clarifying the existence of the clinically invisible, early stages of AKs on chronically UV‐exposed skin without showing clinically evident features of AK.Methods46 volunteers (26 females and 20 males) aged 50+ with signs of moderate to severe UV‐damage (photodamage) applied imiquimod 3.75% creme on their entire face every night for a 2‐week period. All participants kept a diary noting onset, severity of inflammatory reactions, and unexpected side effects.ResultsMore than 90% of participants without clinical evidence of AK showed inflammatory reactions on topical treatment with imiquimod on their face demonstrating an interaction between UV‐damaged mutated keratinocytes and the topically applied immunomodifier, thus proofing the presence of subclinical AKs.ConclusionsThe action of imiquimod is not restricted to visible AK lesions, but often includes their vicinity, suggesting that neoplastic processes are frequent at a cellular level, not confined to clinically evident lesions, supporting the concept of field cancerization. Thus, subclinical AKs do exist in an early, macroscopically invisible state and may be targeted by imiquimod or 5‐FU. At this stage, AKs are being treated before diagnosis by usual clinical means, and well before potential progression to invasive squamous cell carcinoma (SCC). Eventually, imiquimod 3.75% cream could be recommended in UV‐exposed skin to prevent the presumptive development of AK and later on, early SCC.
Environmental Risk Factors for Pediatric Epistaxis vary by Climate Zone
Authors: Wei Eric X. , Green Allen , Chang Michael T. , Hwang Peter H. , Sidell Douglas R. , Qian Z. Jason 
Published: August 2023

Introduction and ObjectivePrior studies have provided variable results regarding environmental risk factors for epistaxis. These studies were conducted in varying climate zones, which may explain discrepancies in results. The objective of this study is to investigate correlations between season, temperature, and humidity on frequency of pediatric epistaxis across climate zones.MethodsChildren seen in the outpatient setting for epistaxis were identified from the 2007–2010 IBM MarketScan database. Climate zones were assigned according to International Energy Conservation Code (IECC) classification, where temperature zones in the United States and territories were assigned on an ordinal scale from 1 (tropical) to 8 (subarctic), and humidity zones were categorized as moist, dry, or marine. The control population was a sample of all well‐child visits matched by age and county.ResultsWe identified 184,846 unique children seen for epistaxis and 1,897,012 matched controls. Moderate temperature zones were associated with lower odds of epistaxis compared with the hottest and coldest zones. Humidity was associated inversely with epistaxis rates in moderate temperature zones but was not a significant predictor of epistaxis in climates with extreme heat. Additionally, summer was associated with lower odds of epistaxis compared to winter. Interestingly, however, there were significantly higher rates of cautery procedures during summer months, driven largely by increased procedures performed in clinic, as opposed to the operating room or emergency room.ConclusionsEnvironmental risk factors for epistaxis vary by climate zone. The model presented reconciles prior reports and may allow for more personalized clinical management based on regional climate.Level of Evidence3 Laryngoscope, 134:1450–1456, 2024
Cattle–compost–soil: The transfer of antibiotic resistance in livestock agriculture
Authors: Abbas Fadhel , Thomas Phil , Cully‐Duse Bianca , Andronicos Nicholas M. , Winter Gal 
Published: August 2023

AbstractAntibiotic resistance is a major global health threat. Agricultural use of antibiotics is considered to be a main contributor to the issue, influencing both animals and humans as defined by the One Health approach. The purpose of the present study was to determine the abundance of antibiotic‐resistant bacterial populations and the overall bacterial diversity of cattle farm soils that have been treated with animal manure compost. Soil and manure samples were collected from different sites at Tullimba farm, NSW. Cultures were grown from these samples in the presence of 11 commonly used antibiotics and antibiotic‐resistant bacteria (ARB) colonies were identified. Soil and manure bacterial diversity was also determined using 16S ribosomal RNA next‐generation sequencing. Results showed that ARB abundance was greatest in fresh manure and significantly lower in composted manure. However, the application of composted manure on paddock soil led to a significant increase in soil ARB abundance. Of the antibiotics tested, the number of ARB in each sample was greatest for antibiotics that inhibited the bacterial cell wall and protein synthesis. Collectively, these results suggest that the transfer of antibiotic resistance from composted animal manure to soil may not be solely mediated through the application of live bacteria and highlight the need for further research into the mechanism of antibiotic resistance transfer.
27‐Hydroxycholesterol Drives the Spread of α‐Synuclein Pathology in Parkinson's Disease
Authors: Dai Lijun , Wang Jiannan , Zhang Xingyu , Yan Mingmin , Zhou Lingyan , Zhang Guoxin , Meng Lanxia , Chen Liam , Cao Xuebing , Zhang Zhaohui , Wang Gaohua , Zhang Zhentao 
Published: August 2023

AbstractBackgroundThe accumulation and aggregation of α‐synuclein (α‐Syn) are characteristic of Parkinson's disease (PD). Epidemiological evidence indicates that hyperlipidemia is associated with an increased risk of PD. The levels of 27‐hydroxycholesterol (27‐OHC), a cholesterol oxidation derivative, are increased in the brain and cerebrospinal fluid of patients with PD. However, whether 27‐OHC plays a role in α‐Syn aggregation and propagation remains elusive.ObjectiveThe aim of this study was to determine whether 27‐OHC regulates α‐Syn aggregation and propagation.MethodsPurified recombinant α‐Syn, neuronal cultures, and α‐Syn fibril‐injected mouse model of PD were treated with 27‐OHC. In addition, CYP27A1 knockout mice were used to investigate the effect of lowering 27‐OHC on α‐Syn pathology in vivo.Results27‐OHC accelerates the aggregation of α‐Syn and enhances the seeding activity of α‐Syn fibrils. Furthermore, the 27‐OHC‐modified α‐Syn fibrils localize to the mitochondria and induce mitochondrial dysfunction and neurotoxicity. Injection of 27‐OHC‐modified α‐Syn fibrils induces enhanced spread of α‐Syn pathology and dopaminergic neurodegeneration compared with pure α‐Syn fibrils. Similarly, subcutaneous administration of 27‐OHC facilitates the seeding of α‐Syn pathology. Genetic deletion of cytochrome P450 27A1 (CYP27A1), the enzyme that converts cholesterol to 27‐OHC, ameliorates the spread of pathologic α‐Syn, degeneration of the nigrostriatal dopaminergic pathway, and motor impairments. These results indicate that the cholesterol metabolite 27‐OHC plays an important role in the pathogenesis of PD.Conclusions27‐OHC promotes the aggregation and spread of α‐Syn. Strategies aimed at inhibiting the CYP27A1‐27‐OHC axis may hold promise as a disease‐modifying therapy to halt the progression of α‐Syn pathology in PD. © 2023 International Parkinson and Movement Disorder Society.
Expanding the allelic spectrum of ELOVL4‐related autosomal recessive neuro‐ichthyosis
Authors: Alabdulrazzaq Fatima , Alanzi Talal , Al‐Balool Haya H. , Gardham Alice , Wakeling Emma , Leitch Harry G. , AlSayed Moeenaldeen , Abdulrahim Maha , Aladwani Abdulaziz , Romito Antonio , Kampe Kapil , Ferdinandusse Sacha , Aboelanine Ashraf H. , Abdullah Amira , Alwadani Amal , Bastaki Laila , Vaz Frédéric M. , Bertoli‐Avella Aida M. , Marafi Dana 
Published: August 2023

AbstractBackgroundVery long‐chain fatty acids (VLCFAs) composed of more than 20 carbon atoms are essential in the biosynthesis of cell membranes in the brain, skin, and retina. VLCFAs are elongated beyond 28 carbon atoms by ELOVL4 enzyme. Variants in ELOVL4 are associated with three Mendelian disorders: autosomal dominant (AD) Stargardt‐like macular dystrophy type 3, AD spinocerebellar ataxia, and autosomal recessive disorder congenital ichthyosis, spastic quadriplegia and impaired intellectual development (ISQMR). Only seven subjects from five unrelated families with ISQMR have been described, all of which have biallelic single‐nucleotide variants.MethodsWe performed clinical exome sequencing on probands from four unrelated families with neuro‐ichthyosis.ResultsWe identified three novel homozygous ELOVL4 variants. Two of the families originated from the same Saudi tribe and had the exact homozygous exonic deletion in ELOVL4, while the third and fourth probands had two different novel homozygous missense variants. Seven out of the eight affected subjects had profound developmental delay, epilepsy, axial hypotonia, peripheral hypertonia, and ichthyosis. Delayed myelination and corpus callosum hypoplasia were seen in two of five subjects with brain magnetic rosonance imaging and cerebral atrophy in three.ConclusionOur study expands the allelic spectrum of ELOVL4‐related ISQMR. The detection of the same exonic deletion in two unrelated Saudi family from same tribe suggests a tribal founder mutation.
Managing juvenile idiopathic arthritis within the context of their life: What we learnt from children and youth living with juvenile idiopathic arthritis and their parents
Authors: Currie G. R. , Kennedy B. L. , S. M. Benseler , R. S. M. Yeung , J. F. Swart , S. J. Vastert , N. M. Wulffraat , M. M. A. Kip , MacKean Gail , Marshall D. A. 
Published: August 2023

AbstractIntroductionJuvenile idiopathic arthritis (JIA) is the most common rheumatic disease in children and causes short‐ and long‐term disability. Optimal management requires pharmacologic and non‐pharmacologic interventions. Few studies have explored the youth and family experience of the management of JIA. This study's objective was to explore the management experience of youth with JIA and their parents.MethodsThis qualitative study used semi‐structured interviews with youth 12–18 years of age with JIA receiving biological medication and parents of children with JIA on biological medication. Participants were recruited in clinics using convenience sampling. A thematic analysis approach was employed for data analysis.ResultsNine youth and 14 parents participated. Four themes were identified that encompassed an overarching theme of participants managing JIA within the context of their life: aspects of life affected by JIA and its management, lived experience with JIA management, medication decision‐making, and involvement in decision‐making. Juvenile idiopathic arthritis management is situated within the context of their life but is normally (outside acute events) not central.ConclusionTwo dimensions were added to those in the literature: parents' overall approaches to health and the sense of urgency surrounding decision‐making. Our findings reinforce the importance of person‐ and family‐centred care in paediatric rheumatology. That is, identifying what matters most to youth and their parents given their current life circumstances to provide a foundation for discussions of how they want to manage their JIA.
Development of a consumer involvement strategy for a small university‐based musculoskeletal research centre
Authors: Nelligan Rachel K. , Haber Travis , Bennell Kim L. , Hinman Rana S. , Bidgood Neil , Marlow Jennifer , Lawford Belinda J. 
Published: August 2023

AbstractObjectiveTo develop a Consumer Involvement Strategy which adheres to best practice recommendations and is feasible to implement in a small musculoskeletal research centre funded solely by external grants.MethodsThe Strategy development involved five collaborative and iterative stages: (1) conceptualisation and initial consultation; (2) formation of the Consumer Involvement Strategy Action Group; (3) defining the scope and developing the strategy; (4) consultation and refinement; and (5) presentation and implementation. The final three stages were overseen by a Consumer Involvement Strategy Action Group comprising two post‐doctoral research fellows, a PhD student representative, and two consumers (people with osteoarthritis), all with experience in consumer involvement activities in research.ResultsThe final strategy aligns with best practice recommendations and includes five unique levels of consumer involvement that were devised to encompass the wide variety of consumer involvement activities across the research centre. It includes a policy document with five strategic aims, each supported by an implementation plan, and includes a suite of resources for researchers and consumers to support its application.ConclusionThe Consumer Involvement Strategy and its described development may serve as a template for other research teams facing similar resource constraints, both at a national and international level.
Lake Trout population dynamics in the Northern Refuge of Lake Michigan: Importance of stocking rate
Authors: Madenjian Charles P. , Dieter Patricia M. , Desorcie Timothy J. , Lengnick Stephen A. , O'Brien Timothy P. , Benes Lynn M. , Farha Steven A. , Leonhardt Benjamin S. 
Published: August 2023

Abstract

Objective
The Northern Refuge of Lake Michigan was established under the auspices of the Great Lakes Fishery Commission in 1985 as an additional step toward restoring a self-sustaining Lake Trout Salvelinus namaycush population to the lake. The overall goal of our study was to assess progress toward Lake Trout rehabilitation in the Northern Refuge through 2021.

Methods
We conducted annual (1992–2021) gill-net surveys in the fall to assess the adult population and beam trawl surveys in the spring to assess naturally reproduced age-0 Lake Trout.

Result
Spawner abundance averaged 45 fish • 305 m of gill net−1 • day−1 during 1992–1999, just 4 fish • 305 m of gill net−1 • day−1 during 2000–2014, and then 67 fish • 305 m of gill net−1 • day−1 during 2018–2021. Sea Lamprey Petromyzon marinus wounding rate decreased by nearly 90% between the 2000–2014 and 2015–2021 periods. The average annual mortality rate of adult Lake Trout decreased from 43% during the 1990s and 2000s to 22% during 2015–2021. All of these population dynamics were partly driven by changes in Lake Trout stocking rates, which declined by roughly 50% during 1994–1996 but then increased roughly twofold during 2006–2010 and remained at this higher level during 2010–2018. In 2021, early signs of natural recruitment of Lake Trout became evident. Beam trawling during June 2021 yielded a wild age-0 Lake Trout, the first ever caught since the surveys began in 1992. In addition, 15 (4% of total catch) of the Lake Trout caught in the fall 2021 gill-net survey were unclipped (wild) fish. Estimated ages of these wild fish indicated that natural recruitment had begun sometime around 2015.

Conclusion
With Alewife Alosa pseudoharengus abundance in Lake Michigan at record low levels, Sea Lamprey wounding rate greatly reduced, and Lake Trout spawner abundance at relatively high levels, the outlook for Lake Trout rehabilitation in the Northern Refuge holds promise.
Spatiotemporal vaccine allocation policies for epidemics with behavioral feedback dynamics
Authors: Barth Julius , Li Su , Aprahamian Hrayer , Gupta Diwakar 
Published: August 2023

AbstractMotivated by the COVID‐19 pandemic, we study how a public health authority may allocate vaccines from a limited stockpile to different jurisdictions over time. We propose an epidemiological model with time‐varying contact rates determined by a stylized behavioral feedback mechanism to reflect multi‐wave transmission dynamics. We evaluate the performance of various information‐sensitive allocation policies (e.g., allocation proportional to local incidence) as alternatives to the widely used pro‐rata policy. We also obtain optimized allocation strategies under the proposed epidemiological model with fairness and implementable freeze‐period constraints. For the case of a multi‐wave epidemic as represented by our compartmental model with behavioral feedback, we find that none of the alternative policies offers consistently more efficient allocations than a simple pro‐rata policy across a broad range of behavioral parameter settings. In fact, in some cases the alternative policies may actually result in less efficient allocations than the pro‐rata policy. Thus our results support the conclusion that the widely used pro‐rata policy can be well justified because it is simple to explain/implement and does not cause unexpected adverse effects. However, if policy makers are willing to invest in more tailored strategies based on numerical optimization, then the identified optimized strategies are a more favorable option as they allow for a more efficient allocation of vaccines.
Optimizing vaccine distribution in developing countries under natural disaster risk
Authors: Seranilla Bonn Kleiford , Löhndorf Nils 
Published: August 2023

AbstractFor many developing countries, COVID‐19 vaccination roll‐out programs are not only slow but vaccination centers are also exposed to the risk of natural disaster, like flooding, which may slow down vaccination progress even further. Policy‐makers in developing countries therefore seek to implement strategies that hedge against distribution risk in order for vaccination campaigns to run smoothly and without delays. We propose a stochastic‐dynamic facility location model that allows policy‐makers to choose vaccination facilities while accounting for possible facility failure. The model is a multi‐stage stochastic variant of the classic facility location problem where disruption risk is modelled as a binary multivariate random process–a problem class that has not yet been studied in the extant literature. To solve the problem, we propose a novel approximate dynamic programming algorithm which trains the shadow price of opening a flood‐prone facility on historical data, thereby alleviating the need to fit a stochastic model. We trained the model using rainfall data provided by the local government of several major cities in the Philippines which are exposed to multiple flooding events per year. Numerical results demonstrate that the solution approach yields approximately 30%–40% lower cost than a baseline approach that does not consider the risk of flooding. Recommendations based on this model were implemented following a collaboration with two large cities in the Philippines which are exposed to multiple flooding events per year.
Antiproliferative Activities and SwissADME Predictions of Physicochemical Properties of Carbonyl Group‐Modified Rotenone Analogues
Authors: Hernandez Rajelle D. , Genio Frances Abygail F. , Casanova Jannelle R. , Conato Marlon T. , Paderes Monissa C. 
Published: August 2023

AbstractRotenone is a naturally occurring compound shown to exhibit antiproliferative activity against various cancer cell lines, indicating its potential as a lead anticancer agent. However, its toxicity against normal cells has prompted further investigation and chemical modifications. In this study, a library of carbonyl group‐modified rotenone derivatives was synthesized and evaluated for their antiproliferative activities against MCF‐7 breast cancer cells, A549 human lung carcinoma cells, and HCT116 human colorectal cancer cells using 3‐(4, 5‐dimethylthiazolyl‐2)‐2, 5‐diphenyltetrazolium bromide (MTT) assay. The results showed several promising compounds that inhibited cell proliferation. Specifically, the oxime and alcohol rotenone derivatives exhibited antiproliferative activities against all 3 cancer cell lines, while the ethoxy, carbamate, and alkene derivatives are selective against MCF‐7 (IC50=5.72 μM), HCT116 (IC50=8.86 μM), and A549 (IC50=0.11 μM), respectively. SwissADME analysis showed that the physicochemical properties and drug‐likeness of the synthesized rotenone derivatives were within the set limits, suggesting the favorable characteristics of these compounds for drug development. The findings obtained in this work highlight the potential of rotenone derivatives as promising chemotherapeutic candidates.
An analysis of the resource use and costs of febrile neutropenia events in pediatric cancer patients in Australia
Authors: Vargas Constanza , Haeusler Gabrielle M. , Slavin Monica A. , Babl Franz E. , Mechinaud Francoise , Phillips Robert , Thursky Karin , Lourenco Richard De Abreu ,   the Australian PICNICC Study Group
Published: August 2023

AbstractBackgroundFebrile neutropenia (FN) in children with cancer generally requires in‐hospital care, but low‐risk patients may be successfully managed in an outpatient setting, potentially reducing the overall healthcare costs. Updated data on the costs of FN care are lacking.MethodsA bottom‐up microcosting analysis was conducted from the healthcare system perspective using data collected alongside the Australian PICNICC (Predicting Infectious Complications of Neutropenic sepsis In Children with Cancer) study. Inpatient costs were accessed from hospital administrative records and outpatient costs from Medicare data. Costs were stratified by risk status (low/high risk) according to the PICNICC criteria. Estimated mean costs were obtained through bootstrapping and using a linear model to account for multiple events across individuals and other clinical factors that may impact costs.ResultsThe total costs of FN care were significantly higher for FN events classified as high‐risk ($17,827, 95% confidence interval [CI]: $17,193–$18,461) compared to low‐risk ($10,574, 95% CI: $9818–$11,330). In‐hospital costs were significantly higher for high‐risk compared to low‐risk events, despite no differences in the cost structure, mean cost per day, and pattern of resource use. Hospital length of stay (LOS) was the only modifiable factor significantly associated with total costs of care. Excluding antineoplastics, antimicrobials are the most commonly used medications in the inpatient and outpatient setting for the overall period of analysis.ConclusionThe FN costs are driven by in‐hospital admission and LOS. This suggests that the outpatient management of low‐risk patients is likely to reduce the in‐hospital cost of treating an FN event. Further research will determine if shifting the cost to the outpatient setting remains cost‐effective overall.