bluuebunny/crossref_metadata_2025_split huggingface dataset:
P27.18.A RADIOGRAPHIC AND CLINICAL RESPONSE OF SACRAL WHO GRADE 2 MYXOPAPILLARY EPENDYMOMA WITH PROTON BEAM RADIATION AND TEMOZOLOMIDE WITHOUT SURGICAL RESECTION
Authors: Valerius A , Sener U , Rose P , Breen W , Lehrer E , Thomsen A , Baykal D 
Published: October 2024

Abstract

BACKGROUND
Myxopapillary ependymomas (MPE) are slow-growing tumors of the spine typically involving the medullary conus and cauda equina. MPE is regularly managed with surgical resection with radiation therapy reserved for cases where gross total resection cannot be achieved. Management of inoperable cases represents a clinical challenge. No systemic therapy is approved for treatment of MPE. Addition of chemotherapy may improve outcomes for cases not amenable to resection.

MATERIAL AND METHODS
We report feasibility and preliminary efficacy of combination treatment with proton beam radiation therapy and temozolomide chemotherapy for a patient with large, unresectable MPE.

RESULTS
A 19-year-old female presented with one year of gradually worsening hip and back pain despite treatment with physical therapy. MRI Lumbar spine identified a destructive and expansile T2-heterogenous and hyperintense intraosseous mass (14 x 12 x 13 cm) with extraosseous expansion involving the sacrum, coccyx, and left SI joint with abnormal soft tissue enhancement extending along the posterior spine. No additional lesions were identified on neuro-axis imaging. Biopsy of the mass was consistent with a WHO grade 2 myxopapillary ependymoma. Standard treatment of care would include complete surgical resection. Unfortunately, this would require a morbid procedure in an en block fashion with immediate and permanent loss of bowel, bladder, sexual, and ambulatory function in a young patient whose primary symptom was pain and mild weakness. It was therefore elected to treat the patient in an unconventional approach and begin with proton beam radiation therapy (59.4 Gy in 33 fractions) with concurrent temozolomide followed by 6 cycles of adjuvant temozolomide. Mild clinical improvement and significant radiographic response were achieved (size reduced to 8 x 7 x 11 cm).

CONCLUSION
This case suggests a potential role for use of proton radiation therapy with concurrent and adjuvant temozolomide for management of myxopapillary ependymoma not amenable to surgical resection.
Exposure to procedural ionizing radiation and cancer risk among physicians
Authors: Simpson A N , Sutradhar R , McArthur E , Tanuseputro P , Bharatha A , Ray J G 
Published: October 2024

Abstract

Background
Physicians in certain specialities are routinely exposed to procedural ionizing radiation. Their risk of cancer is unknown, including by cancer sub-types.

Aims
To assess cancer risk among exposed physicians.

Methods
This population-based case–control study was completed in Ontario, Canada, where healthcare is universal, using linkage of physician billing claims to a province-wide cancer registry. Up to five cancer-free physician controls were matched to each cancer-affected physician, by sex, and both age at and year of, entry into practice. Cumulative exposure to procedural ionizing radiation was captured by physician billing claims. Conditional logistic regression generated an odds ratio (OR) of cancer per 1000 procedures performed and as a binary exposure comparing physicians above the upper 95th percentile cumulative number of procedures (≥200) to those below this cut point.

Results
Mean (standard deviation) age of the 1265 cases and 5772 non-cancer controls was 39.7 (10.7) and 37.7 (9.0) years, and 45% and 49% were female, respectively. After a median (interquartile ranges) of 13.0 (6.9–20.4) and 12.5 (6.5–20.1) years of lookback among cases and controls, the OR of cancer was 1.02 (95% confidence interval 0.99–1.05; P = NS) per 1000 additional procedures performed. Modelling the cumulative exposure to procedures nonlinearly did not change the observed association (P &gt; 0.40 for each). Comparing physicians above versus below the upper 95th percentile cumulative number of procedures, the OR of cancer was 1.23 (95% confidence interval 0.75–2.01, P = NS).

Conclusions
Physician exposure to procedural ionizing radiation was not associated with a higher risk of cancer. Measures that minimize radiation exposure should continue.
Optimizing Lumefantrine Dosing for Young Children in High-Malaria-Burden Countries Using Pharmacokinetic-Pharmacodynamic Simulations
Authors: Simeon Segolene , Hughes Emma , Wallender Erika , P. Solans Belén , Savic Rada 
Published: October 2024

Abstract

Background
Artemether-lumefantrine is the most widely used treatment for uncomplicated malaria and it is dosed based on weight bands according to World Health Organization (WHO) guidelines. However, children are vulnerable to underdosing. Inadequate dosing can lead to treatment failure and drug resistance.

Methods
Nutritional parameters for 372 363 children &lt;5 years old in 25 high-malaria-burden countries were acquired from the Demographic and Health Surveys program. Prevalence of attaining day 7 lumefantrine concentrations ≥200 ng/mL and remaining reinfection free for 42 days were evaluated using a simulation-based approach with a population pharmacokinetic-pharmacodynamic model. Besides the WHO-recommended lumefantrine dosing regimen (twice daily for 3 days), we explored 3 adjusted regimens: extended (2 extra days of dosing), increased (1 extra 120-mg tablet per dose), and intensified (thrice daily for 3 days). We also explored an alternative method dosing malnourished children based on expected weight for age.

Results
We estimated that 75% of children reached the 200 ng/mL lumefantrine threshold and 77% were malaria free for 42 days when using WHO treatment guidelines. By switching to the alternative dosing method, 5% more children achieved target lumefantrine levels; 22% more achieved the target using the alternative dosing and the extended regimen. With combined alternative plus extended dosing, 97% of children reached 200 ng/mL lumefantrine and 88% were malaria free for 42 days.

Conclusions
This study highlights the inadequacies of weight-based lumefantrine dosing for young and underweight children and supports the need of clinical trials using extended dosing based on expected weight in malnourished children.
Revisiting immunity vs. exposure in schistosomiasis: A mathematical modeling study of delayed concomitant immunity
Authors: Milne Gregory C , Oettle Rebecca C , Whittaker Charles , Kabatereine Narcis B , Basáñez Maria-Gloria , Webster Joanne P , Walker Martin , Wilson Shona 
Published: October 2024

Abstract
The relative contributions of exposure vs. acquired immunity to the epidemiology of human schistosomiasis has been long debated. While there is considerable evidence that humans acquire partial immunity to infection, age- and sex-related contact patterns with water bodies contaminated with infectious cercarial schistosome larvae also contribute to typical epidemiological profiles of infection. Here, we develop a novel schistosome transmission model that incorporates both partially protective “delayed concomitant” acquired immunity—stimulated by dying worms—and host age- and sex-dependent patterns of exposure. We use a contemporary Bayesian approach to fit the model to historical individual data on exposure to infectious cercaria, eggs per gram of feces, and immunoglobulin E antibodies specific to Schistosoma mansoni Tegumental-Allergen-Like protein 1 collected from a highly endemic community in Uganda, estimating the relative contributions of exposure and acquired immunity. We find that model variants incorporating or omitting delayed concomitant immunity describe equally well the age- and sex-specific immunoepidemiological patterns observed before intervention and 18 months after treatment. Over longer time horizons, we find that acquired immunity creates subtle differences in immunoepidemiological profiles during routine mass drug administration that may confer resilience against elimination. We discuss our findings in the broader context of the immunoepidemiology of schistosomiasis.
Pre-emptive pharmacogenetic testing in the acute hospital setting: a cross-sectional study
Authors: McDermott John H , Burke Kerry , Fullerton Neil , O’Sullivan James , Alex Aleina , Ingham Amy , Sharma Videha , Godfrey Nicola , Odudu Aghogho , Syed Tania , Stevens Andrew , Beynon Rhys , Greaves Nicholas , Akam Daniel , Mirza Selman , Wilson Paul , Wright Stuart , Payne Katherine , Newman William G 
Published: October 2024

Abstract

Background
Pharmacogenetic-guided prescribing can be used to improve the safety and effectiveness of medicines. There are several approaches by which this intervention might be implemented in clinical practice, which will vary depending on the health system and clinical context.

Aim
To understand the clinical utility of panel-based pharmacogenetic testing in patients admitted acutely to hospital and to establish variables that predict if an individual might benefit from the intervention.

Design
A cross-sectional study recruiting patients admitted acutely to hospital.

Methods
Participants underwent panel-based pharmacogenetic testing, and their genetic results were analysed in their context of the medicines they had been exposed to as an inpatient. The primary outcome was the proportion of patients with clinically actionable gene–drug interactions. Individual variables that predict the clinical utility of pharmacogenetic testing were established via logistic regression.

Results
Genetic and prescribing data were available for 482 inpatients (55% male; median age 61.2 years; range: 18–96), 97.9% of whom carried a pharmacogenetic result of interest. During their admission, 79.5% of patients were exposed to a medicine for which there is pharmacogenetic prescribing guidance available. Just under one in seven individuals (13.7%) had a clinically actionable gene–drug interaction. Increasing age (&gt;50 years) was positively correlated with the likelihood (2.7-fold increased risk) of having a clinically actionable interaction.

Conclusions
These findings demonstrate the potential scale, and potential clinical utility, of pharmacogenetic testing as an intervention, highlighting the need to develop infrastructure to support healthcare professionals make use of this emerging tool.
Curcumin-incorporated EGCG-based nano-antioxidants alleviate colon and kidney inflammation via antioxidant and anti-inflammatory therapy
Authors: Pan Qingqing , Xie Li , Zhu Huang , Zong Zhihui , Wu Di , Liu Rong , He Bin , Pu Yuji 
Published: October 2024

Abstract
Natural remedies are gaining attention as promising approaches to alleviating inflammation, yet their full potential is often limited by challenges such as poor bioavailability and suboptimal therapeutic effects. To overcome these limitations, we have developed a novel nano-antioxidant (EK) based on epigallocatechin gallate (EGCG) aimed at enhancing the oral and systemic bioavailability, as well as the anti-inflammatory efficacy, of curcumin (Cur) in conditions such as acute colon and kidney inflammation. EK is synthesized using a straightforward Mannich reaction between EGCG and L-lysine (K), resulting in the formation of EGCG oligomers. These oligomers spontaneously self-assemble into nanoparticles with a spherical morphology and an average diameter of approximately 160 nm. In vitro studies reveal that EK nanoparticles exhibit remarkable radical-scavenging capabilities and effectively regulate redox processes within macrophages, a key component in the body’s inflammatory response. By efficiently encapsulating curcumin within these EK nanoparticles, we create Cur@EK, a formulation that demonstrates a synergistic anti-inflammatory effect. Specifically, Cur@EK significantly reduces the levels of pro-inflammatory cytokines TNF-α and IL-6 while increasing the anti-inflammatory cytokine IL-10 in lipopolysaccharide-stimulated macrophages, highlighting its potent anti-inflammatory properties. When administered either orally or intravenously, Cur@EK shows superior bioavailability compared to free curcumin and exhibits pronounced anti-inflammatory effects in mouse models of ulcerative colitis and acute kidney injury. These findings suggest that the EK nano-antioxidant platform not only enhances the bioavailability of curcumin but also amplifies its therapeutic impact, offering a promising new avenue for the treatment and management of inflammation in both oral and systemic contexts.
FAM13A polymorphism is associated with a usual interstitial pneumonia pattern in patients with systemic sclerosis-associated interstitial lung disease
Authors: Bernstein Elana J , Boin Francesco , Elicker Brett , Luo Yiming , Ren Yawen , Zhang Meng , Varga John , Assassi Shervin 
Published: October 2024

Abstract

Objectives
The MUC5B promoter single nucleotide polymorphism (SNP) rs35705950 has been associated with idiopathic pulmonary fibrosis (IPF) and RA-related interstitial lung disease (ILD), but not with SSc-ILD. We hypothesized that the MUC5B promoter polymorphism or other IPF susceptibility loci are associated with an increased risk for the uncommon SSc-usual interstitial pneumonia (UIP) endophenotype, rather than SSc-ILD in general.

Methods
We performed a cross-sectional study of SSc-ILD patients from four US Scleroderma Programs to investigate the frequency of MUC5B rs35705950 and 12 additional IPF susceptibility loci. SSc-ILD patients were stratified by high resolution chest CT (HRCT) imaging findings into UIP and non-UIP groups. Analysis of HRCTs performed by a thoracic radiologist blinded to participants’ characteristics classified each scan as definite UIP, probable UIP, indeterminate or alternative diagnosis, according to American Thoracic Society criteria.

Results
Four-hundred and eighty-nine SSc-ILD patients were included; 80% were female and 75% were White. Twenty-three (4.7%) patients had a definite UIP pattern. The MUC5B SNP rs35705950 was not associated with a definite UIP pattern in SSc-ILD. In contrast, patients carrying two copies of the IPF risk gene FAM13A minor allele rs2609255 had significantly higher odds of a definite UIP pattern compared with the other patterns (odds ratio 3.40, 95% CI 1.19–9.70), and compared with an alternative diagnosis (odds ratio 3.65, 95% CI 1.25–10.65).

Conclusion
We demonstrated a novel association between FAM13A and SSc-UIP. Contrary to IPF and RA-ILD, the MUC5B promoter polymorphism was not associated with a definite UIP pattern in SSc-ILD.
Genomic epidemiology reveals the variation and transmission properties of SARS-CoV-2 in a single-source community outbreak
Authors: Zhao Ning , He Min , Wang HengXue , Zhu LiGuo , Wang Nan , Yong Wei , Fan HuaFeng , Ding SongNing , Ma Tao , Zhang Zhong , Dong XiaoXiao , Wang ZiYu , Dong XiaoQing , Min XiaoYu , Zhang HongBo , Ding Jie 
Published: October 2024

Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the coronavirus disease 2019 (COVID-19) pandemic, which is still a global public health concern. During March 2022, a rapid and confined single-source outbreak of SARS-CoV-2 was identified in a community in Nanjing municipal city. Overall, 95 individuals had laboratory-confirmed SARS-CoV-2 infection. The whole genomes of 61 viral samples were obtained, which were all members of the BA.2.2 lineage and clearly demonstrated the presence of one large clade, and all the infections could be traced back to the original index case. The most distant sequence from the index case presented a difference of 4 SNPs, and 118 intrahost single-nucleotide variants (iSNVs) at 74 genomic sites were identified. Some minor iSNVs can be transmitted and subsequently rapidly fixed in the viral population. The minor iSNVs transmission resulted in at least two nucleotide substitutions among all seven SNPs identified in the outbreak, generating genetically diverse populations. We estimated the overall transmission bottleneck size to be 3 using 11 convincing donor–recipient transmission pairs. Our study provides new insights into genomic epidemiology and viral transmission, revealing how iSNVs become fixed in local clusters, followed by viral transmission across the community, which contributes to population diversity.
MOR23 deficiency exacerbates hepatic steatosis in mice
Authors: Kang Wesuk , Yang Suhjin , Roh Jiyun , Choi Dabin , Lee Han‐Woong , Lee Jae Hoon , Park Taesun 
Published: October 2024

AbstractHepatic steatosis, a common liver disorder, can progress to severe conditions such as nonalcoholic steatohepatitis and cirrhosis. While olfactory receptors are primarily known for detecting odorants, emerging evidence suggests that they also influence liver lipid metabolism. This study generated a mouse model with a specific knockout of olfactory receptor 23 (MOR23) to investigate its role in hepatic steatosis. MOR23 knockout mice on a normal diet showed a slight increase in liver weight compared to wild‐type (WT) mice. When fed a high‐fat diet (HFD), these knockout mice exhibited accelerated hepatic steatosis, indicated by increased liver weight and hepatic triglyceride levels. Our findings suggest that the cyclic adenosine monophosphate/protein kinase A/AMP‐activated protein kinase pathway is involved in the role of MOR23, leading to the upregulation of peroxisome proliferator‐activated receptor α, peroxisome proliferator‐activated receptor‐γ coactivator 1‐α, and their target β‐oxidation genes in the liver. MOR23 also appeared to regulate lipogenesis and free fatty acid uptake in HFD‐fed mice, potentially by influencing sterol regulatory element‐binding protein 1 activity. Notably, administering a potential MOR23 ligand, cedrene, attenuated hepatic steatosis in WT mice, but these effects were largely nullified in MOR23 knockout mice. These findings provide valuable insights into the in vivo role of MOR23 in hepatic steatosis development.
Control versus Choice in Deciding Career Pathway in Plastic Surgery: The Perfect Ratio
Authors: Davison Steven P. , Evans Gregory , Ball Eleanor , Newman Ashley , Sotile Wayne 
Published: October 2024

Background:
The decisions and components of a career in medicine have changed. Historically, a career selection was often a decision between joining an institution or academic center versus the fiscal risks associated with private practice. This created a relatively simple risk versus reward equation: those in private practice made more money if it went well. The medical landscape has changed immensely, and priorities and remuneration have morphed, including concerns about promoting and sustaining well-being.

Methods:
The authors performed a systematic review of scholarly databases to identify relevant resources to the topic of study. Additionally, the authors relied on their own cumulative experience in the field, including the work of Dr. Wayne Sotile of the Sotile Center for Physician Resilience.

Results:
The first installment of this article proposes a new model in opposition to the current standard of “risk versus reward” where the tradeoff is instead “control versus choice,” where autonomy is the new risk.

Conclusions:
The five components that make up the majority of the ingredients in a plastic surgery career are clinical practice model, administrative duty, corporate support, academic involvement, and per diem or retainers. Much of finding or developing a practice model that suits the individual is figuring out an acceptable ratio of these ingredients. Inherent to this process is how much authority one has versus instituted control of any form, from hospital to university to insurance company.
THE FIGHT INHERITED RETINAL BLINDNESS! PROJECT
Authors: Simunovic Matthew P. , Moore Anthony T. , Grigg John , Sergouniotis Panagiotis , Mahroo Omar A. , Vincent Andrea , Singh Mandeep , Fischer M. Dominik , Edwards Thomas , Mack Heather , Hogden Michael , Chen Fred K. , Hewitt Alex , Ayton Lauren , Leroy Bart , Jamieson Robyn , Gillies Mark C. , Barthelmes Daniel 
Published: October 2024

Purpose:
To design and build a new disease registry to track the natural history and outcomes of approved gene therapy in patients with inherited retinal diseases.

Methods:
A core committee of six members was convened to oversee the construction of the Fight Inherited Retinal Blindness! module. A further 11 experts formed a steering committee, which discussed disease classification and variables to form minimum datasets using a consensus approach.

Results:
The web-based Fight Inherited Retinal Blindness! registry records baseline demographic, clinical, and genetic data together with follow-up data. The Human Phenotype Ontology and Monarch Disease Ontology nomenclature were incorporated within the Fight Inherited Retinal Blindness! architecture to standardize nomenclature. The registry software assigns individual diagnoses to one of seven broad phenotypic groups, with minimum datasets dependent on the broad phenotypic group. In addition, minimum datasets were agreed on for patients undergoing approved gene therapy with voretigene neparvovec (Luxturna). New patient entries can be completed in 5 minutes, and follow-up data can be entered in 2 minutes.

Conclusion:
Fight Inherited Retinal Blindness! is an organized, web-based system that uses observational study methods to collect uniform data from patients with inherited retinal disease to track natural history and (uniquely) treatment outcomes. It is free to users who have control over their data.
Patient perspectives towards skin of color clinics: results from a survey study
Authors: Cao Severine , Thomas Reinie , Mansour Meghan , Ramirez Juliana L. , Hile Grace , Castanedo-Tardan Mari Paz , Eshaq Milad 
Published: October 2024

Background:Skin of color clinics (SOCCs) are dermatology clinics that provide specialized care for patients with melanated skin. Little is known about patient perceptions and attitudes toward these clinics.Objective:We sought to perform a survey study to assess the opinions of patients of color previously seen in our dermatology department toward SOCC.Methods:A 14-question survey was sent by email to patients of color seen at our institution between January 1, 2015 and December 31, 2021.Results:Out of 264 participants who completed the survey, 176 (66.7%) indicated they would prefer to be seen in a SOCC and 88 (33.3%) preferred to be seen in a general dermatology clinic (GDC). Clinic choice varied significantly by ethnicity, with Black/African American participants being the most likely to prefer SOCC over GDC than other races/ethnicities. Those interested in SOCC were primarily motivated by a search for expertise in the skin of color (SOC) and did not have a preference for the skin color of the SOCC dermatologist. Those interested in GDC were happy with their current care.Limitations:This study was limited by the single-center design and sample bias.Conclusion:Our results overall provide positive patient feedback for the creation of SOCCs as centers for expertise in SOC. The preference for SOCC varied by race/ethnicity, highlighting that clinic choice is best left to the patient.