bluuebunny/crossref_metadata_2025_split huggingface dataset:
Utility of genomic testing in children, adolescents, and young adults with cancer
Authors: Debortoli Emily , McGahan Ella , Yanes Tatiane , Berkman Jennifer , Fuentes-Bolanos Noemi , Milch Vivienne , Steinberg Julia , McInerney-Leo Aideen 
Published: September 2024

Abstract
Genomic testing can inform the diagnosis and personalize management of cancers in children, adolescents, and young adults (CAYA). This scoping review explored the clinical utility and impact of genomic testing in general CAYA cancer cohorts. Relevant records published in English between 2017 and 2024 were identified by searching PubMed. 36 studies (32 original articles; 4 reviews) were identified on genomic testing in CAYA cancers, most of which were advanced cancers. Studies internationally reported that approximately 16%-18% of CAYAs with cancer carry an associated pathogenic germline variant where 40% are de novo, and can guide treatment (eg, DNA repair gene variants). Somatic variants, predominantly copy number or structural rearrangements, inform diagnosis in up to 95% of primary cancers. Between 18% and 69% of patients have a somatic variant with a matched therapy, but only one third receive the genomic-guided recommendation, predominantly due to declining patient condition. Few studies evaluated the impact of matched therapies on response and survival. Combining comprehensive DNA and RNA sequencing maximises sensitivity. Circulating tumour DNA was detected in most primary cancers and shows high concordance with tumour tissue. In conclusion, genomic testing of CAYA cancers is feasible, informs diagnoses and guides personalised care. Further research is needed on response to genomic-guided treatments.
Disparities in the utilization of magnetic resonance imaging for prostate cancer detection: a population-based study
Authors: El Khoury Christiane J , Freedland Stephen J , Gandhi Krupa , Keith Scott W , Nikita Nikita , Shaver Amy , Sharma Swapnil , Kelly W M Kevin , Lu-Yao Grace 
Published: September 2024

Abstract

Background
Racial disparities exist in prostate cancer care and outcomes. Ultrasound-guided biopsy may miss a sizeable portion of clinically significant prostate cancer, while magnetic resonance imaging (MRI) improves its detection. This study aimed to investigate demographic and socioeconomic status–related factors influencing MRI use for prostate cancer detection.

Methods
Surveillance, Epidemiology, and End Results Program–Medicare data were used to assess use of prediagnostic MRI in 90 908 patients with a diagnosis of primary prostate cancer (2012-2019). Modified Poisson regression models adjusted for socioeconomic factors such as income, education, Medicare buy-in, and dual eligibility, were used to examine factors associated with MRI use. All statistical tests were 2 sided.

Results
Prediagnostic MRI use increased substantially between 2012 (3.8%) and 2019 (32.6%). The disparity in utilization between non-Hispanic Black and non-Hispanic White patients decreased by more than half, from 43% (relative risk [RR] = 0.57, 95% confidence interval [CI] = 0.48 to 0.67) in 2012 to 20% (RR = 0.80, 95% CI = 0.74 to 0.86) in 2019. Rural residents were 35% less likely (RR = 0.65, 95% CI = 0.61 to 0.69) to undergo MRI, while individuals in the US Census Central (vs West) region of the United States were 49% less likely (RR = 0.49, 95% CI = 0.48 to 0.51). No significant disparities in MRI use were identified between individuals 75 years of age and older and individuals aged 64 to 75 years. Socioeconomic status factors associated with MRI use were income, education, Medicare buy-in, and dual eligibility.

Conclusions
This study revealed increased MRI utilization over time, including among individuals 75 years of age and older. Racial disparities decreased, while wide urban-rural disparities remained. Targeted public health interventions should focus on geographical factors because urban or rural designations and US region were associated with the most prominent disparities. Future research should explore pathways contributing to these disparities by using a multidisciplinary approach, including geographical studies, to help eliminate health-care inequities.
Socioeconomic and urban-rural disparities in genome-matched treatment receipt and survival after genomic tumor testing
Authors: DiBiase Jessica F , Scharnetzki Elizabeth , Edelman Emily , Reed E Kate , Helbig Petra , Rueter Jens , Miesfeldt Susan , Frankenfeld Cara L , Han Paul K J , Jacobs Elizabeth A , Anderson Eric C ,   Maine Cancer Genomics Initiative Working Group, Erickson Nicholette , Movalia Mayur , Skacel Marek , Espinosa Allan , Gupta Ridhi , Kumar Rachit , Polkinghorn Richard , Darus Christopher , Remick Scot , Christman Robert , Rasmussen Karen , Thomas Christian , Brooks Philip , Chodkiewicz Catherine , Harb Antoine , Sinclair Sarah , Rubin Peter , Connelly Elizabeth , Georges Peter , Bourne Jennifer , Choquette Linda , Fasman Ken , Flewellen Cristen , Edelman Emily , Guerrette Lory , Helbig Petra , Mockus Susan , Reed Kate , Rueter Jens , Sanghavi Kunal , Anderson Eric , Awale Sumayo , DiBiase Jessica , DiPalazzo John , Fenton Anny , Frankenfeld Cara , Gutheil Caitlin , Han Paul , Hinton Ally , Kohut Michael , Leeds Susan , Lucas Lee , Scharnetzki Elizabeth , Waterston Leo , Wierda Lisbeth 
Published: September 2024

Abstract

Background
Emerging cancer treatments are often most available to socially advantaged individuals. This study examines the relationship of patient educational attainment, income level, and rurality to the receipt of genome-matched treatment and overall survival.

Methods
Survey and clinical data were collected from patients with cancer (n = 1258) enrolled in the Maine Cancer Genomics Initiative. Logistic regression models examined whether receipt of genome-matched treatment differed by patient education, income, and rurality. Kaplan–Meier curves and Cox regression were conducted to evaluate 12-month mortality. We completed additional exploratory analyses using Kaplan–Meier curves and Cox models stratified by receipt of genome-matched treatment. Logistic and Cox regression models were adjusted for age and gender.

Results
Educational attainment, income level, and rurality were not associated with genome-matched treatment receipt. Of 1258 patients, 462 (36.7%) died within 365 days of consent. Mortality risk was associated with lower educational attainment (hazard ratio [HR] = 1.30, 95% confidence interval [CI] = 1.06 to 1.59; P = .013). No statistically significant differences in mortality risk were observed for income level or rurality. Exploratory models suggest that patients who did not receive genome-matched treatment with lower educational attainment had higher mortality risk (HR = 1.36, 95% CI = 1.09 to 1.69; P = .006). For patients who did receive genome-matched treatment, there was no difference in mortality risk between the education groups (HR = 1.01, 95% CI = 0.56 to 1.81; P &gt; .9).

Conclusion
Although there were no disparities in who received genome-matched treatment, we found a disparity in mortality associated with education level, which was more pronounced for patients who did not receive genome-matched treatment. Future research is warranted to investigate the intersectionality of social disadvantage with clinical outcomes to address survival disparities.
Inclusive measure development: amplifying the voices of adolescents and young adults with spina bifida in a new measure of benefit-finding and growth
Authors: Kritikos Tessa K , Smith Zoe R , Stiles-Shields Colleen , Clark Olivia E , Winning Adrien M , Encalade Alana , Hendrix Millicent , Helgeson Vicki , Holmbeck Grayson 
Published: September 2024

Abstract

Objective
Benefit-finding and growth is an important process across a range of medical populations. However, it has been understudied in the context of lifelong chronic conditions, such as spina bifida (SB). This study aimed to develop a new measure of benefit-finding and growth for youth with SB, confirm its factor structure, and examine its psychometric properties.

Method
To generate items for the new measure, 20 adolescents and young adults with SB completed qualitative interviews regarding their experience of living with SB. Interviews were coded for benefits. Questionnaire items were generated from these benefits, and an expert panel refined the wording of these items. The resultant 31-item measure was shared with six of the 20 participants for feedback and then piloted among 251 youth with SB. The factor structure of the measure was confirmed and reliability and convergent validity were assessed.

Results
Both a one- and four-factor structure were supported. The four factors include: Life Perspectives and Priorities, Personal Characteristics and Traits, Connections and Opportunities, and Problem Solving. Higher total and factor scores represent greater benefit-finding and growth. The measure demonstrated excellent internal consistency (α = 0.95). The new measure also showed significant positive correlations with optimism, positive affect, and life satisfaction.

Conclusions
This study produced a measure of benefit-finding and growth for youth with SB. Clinically, information about what youth with SB perceive to be their areas of strength and growth from their condition provides crucial insight into which factors to enhance in this population.
Mpox Recurrence and Tecovirimat Resistance in a Patient With Advanced Human Immunodeficiency Virus Disease
Authors: Griffith David C , Fall Amary , Carter Mihaela , Traut Caroline C , Sop Joel , Hansoti Bhakti , Gebo Kelly A , Mostafa Heba H , Blankson Joel N 
Published: September 2024

Abstract
We present a case of mpox recurrence in a transgender woman with AIDS. Her recurrent lesions required several courses of antiviral therapy over a 5-month period and her monkeypox viral genome was subsequently noted to have tecovirimat resistance mutations. Interestingly, she developed a robust orthopoxvirus-specific T-cell response.
On the morphology of urosome appendages and their potential function of marine planktonic copepods
Authors: Paffenhöfer G-A , Köster M 
Published: September 2024

Abstract
The goal of this paper is to draw the attention of biological oceanographers to the urosome of zooplankton. The methodology to determine the utilization of urosomes and their sensors for predator recognition is in its infancy. We here describe the potential utilization of setae and their activity of mostly juvenile copepods for the purpose of perceiving predators. Our morphological observations let us assume that calanoid nauplii have few means to perceive predators approaching from the rear and most likely from frontal, as their appendages are moving most of the time. This is being compared to post-nauplii, i.e. copepodid stages, and adults who possess a 2D array of setae on their urosomes, potentially able to perceive predators approaching from the rear. Detailed small-scale observations should reveal the sensor potential of urosomes of nauplii and older stages of planktonic copepods.
PDHX acetylation facilitates tumor progression by disrupting PDC assembly and activating lactylation-mediated gene expression
Authors: Jiang Zetan , Xiong Nanchi , Yan Ronghui , Li Shi-ting , Liu Haiying , Mao Qiankun , Sun Yuchen , Shen Shengqi , Ye Ling , Gao Ping , Zhang Pinggen , Jia Weidong , Zhang Huafeng 
Published: September 2024

Abstract
Deactivation of the mitochondrial pyruvate dehydrogenase complex (PDC) is important for the metabolic switching of cancer cell from oxidative phosphorylation to aerobic glycolysis. Studies examining PDC activity regulation have mainly focused on the phosphorylation of pyruvate dehydrogenase (E1), leaving other post-translational modifications largely unexplored. Here, we demonstrate that the acetylation of Lys 488 of pyruvate dehydrogenase complex component X (PDHX) commonly occurs in hepatocellular carcinoma, disrupting PDC assembly and contributing to lactate-driven epigenetic control of gene expression. PDHX, an E3-binding protein in the PDC, is acetylated by the p300 at Lys 488, impeding the interaction between PDHX and dihydrolipoyl transacetylase (E2), thereby disrupting PDC assembly to inhibit its activation. PDC disruption results in the conversion of most glucose to lactate, contributing to the aerobic glycolysis and H3K56 lactylation-mediated gene expression, facilitating tumor progression. These findings highlight a previously unrecognized role of PDHX acetylation in regulating PDC assembly and activity, linking PDHX Lys 488 acetylation and histone lactylation during hepatocellular carcinoma progression and providing a potential biomarker and therapeutic target for further development.
Effectiveness of low dose cyproterone acetate compared to standard dose in feminizing hormone treatment: a single institutional retrospective pilot study
Authors: Korpaisarn Sira , Arunakul Jiraporn , Chaisuksombat Kewalin , Rattananukrom Teerapong 
Published: September 2024

Abstract

Background
Data regarding the effectiveness of low-dose cyproterone acetate (CPA) in testosterone suppression as feminizing hormone therapy (FHT) in individuals assigned male at birth (AMAB) are sparse.

Aim
To assess the effectiveness in testosterone suppression using low-dose CPA (&lt;25 mg/day) compared to standard-dose CPA (25–50 mg/day) in FHT.

Methods
A retrospective cohort study of 59 individuals AMAB using CPA was done at a tertiary care center in Bangkok, Thailand between January 2014 and July 2022.

Outcomes
The main outcomes included a median time when the testosterone was suppressed (&lt;50 ng/dL), the proportion of individuals AMAB who achieved the targeted testosterone level at 3 months, and the testosterone level at each follow-up. Changes in clinical data were assessed.

Results
Among 59 individuals AMAB, 37 initiated CPA with available testosterone levels at the 3-month follow-up. Twenty-two individuals AMAB started with low-dose CPA (12.5 mg/day), and 15 individuals AMAB started with standard-dose CPA. The median time to reach targeted testosterone was 3 months in both groups (adjusted hazard ratio 0.60, P = .489). At 3 months, 72.7% of those on low-dose CPA and 86.7% of those on standard-dose CPA achieved targeted testosterone (adjusted relative risk 0.85, P = .606). Testosterone levels at all follow-up visits were not significantly different. The standard dose group had higher high-density lipoprotein cholesterol (HDL-C) but lower low-density lipoprotein cholesterol (LDL-C) and alanine aminotransferase (ALT).

Clinical Translation
This study supports a paradigm shift toward using lower-dose CPA in FHT.

Strengths and Limitations
This is one of a few studies showing the effectiveness of low-dose CPA in testosterone suppression within 3 months. Limitations include a small sample size and missing data.

Conclusions
Testosterone suppression is comparable between CPA 12.5 mg/day and the standard dose in FHT.
Policy preferences for medical access in Japan’s remote aging municipalities: Insights from a randomized conjoint experiment
Authors: Matsumoto Azusa , Oku Kenji , Nakagawa Mariko , Saito Hisamitsu , Khan Ghulam Dastgir , Kawata Keisuke , Oki Ichiro , Atsumi Tatsuya , Yoshida Yuichiro 
Published: September 2024

Abstract
Improved means of transportation play a vital role in accessing medical services, particularly in remote and ageing municipalities. In this study, we identify crucial attributes for improving access to medical services in the Shinhidaka and Urakawa municipalities in Japan. Using a randomised conjoint field experiment, we identify individuals’ preferences regarding the time and means of transportation to hospitals that can provide high-level medical services, along with additional tax payments to support these services. We find, inter alia, that respondents have the highest preference for reducing emergency ambulance transportation time to high-function hospitals. We also estimate the minimum average willingness to pay for these services; respondents are willing to pay at least JPY 60,000 (approximately USD 500) additional tax per year to the municipal government if the emergency transportation time to high-function hospitals is reduced. The findings of this study provide valuable insights into addressing the challenges of improving access to medical services in remote areas with an ageing population.
Neurotoxic effects associated with chronic inhalation and oral exposure to glyphosate-based herbicide IN adult rats
Authors: Bifaroni Renata M S , Binotti Giovanna D , Bruneri Karen P , Tavares Maria Eduarda A , Ueda Rose Meire R , Rossi Renata C , Teixeira Giovana R , Corrêa Camila Renata , Nai Gisele Alborghetti 
Published: September 2024

Abstract
The use of glyphosate-based herbicides (GBHs) for agricultural production has increased substantially around the world, as have their residues in the environment. Its effects on the central nervous system and neurotoxicity pathways are still not fully understood. The aim of this study was to evaluate the neurotoxic effect of chronic exposure to a GBH in adult rats. Sixty adult male albino Wistar rats were allocated into 6 groups, 2 control groups, and four GBH exposure groups (n = 10/group). The animals were exposed to two concentrations of GBH, orally and by inhalation: 2.99 × 10−3 grams of active ingredient per hectare (g.a.i./ha) and 7.48 × 10−3 g.a.i./ha. The animals were exposed for six months. Behavioral studies were performed. Brain tissue was collected for histopathological, immunohistochemical, and oxidative stress analyses. Animals exposed by inhalation to GBH spent more time in the central area of the open field test, whereas animals exposed to a high oral concentration of GBH spent less time in the open arms in the elevated plus-maze test. Tissue hyperemia occurred only in animals exposed to high concentrations of GBH. There was a greater thickness of the cerebral cortex and an increase in the expression of the BCL-2 in the animals exposed by inhalation to GBH. There was no difference in the doses of malonaldehyde and protein carbonylation between exposed and unexposed groups. The exposure to GBH caused increased levels of anxiety, regardless of the route, high concentrations caused hyperemia and inhalation exposure cause increased cortex thickness and increased BCl-2 expression.
Mitochondrial membrane potential and oxidative stress interact to regulate Oma1‐dependent processing of Opa1 and mitochondrial dynamics
Authors: Fogo Garrett M. , Raghunayakula Sarita , Emaus Katlynn J. , Torres Torres Francisco J. , Wider Joseph M. , Sanderson Thomas H. 
Published: September 2024

AbstractMitochondrial form and function are regulated by the opposing forces of mitochondrial dynamics: fission and fusion. Mitochondrial dynamics are highly active and consequential during neuronal ischemia/reperfusion (I/R) injury. Mitochondrial fusion is executed at the mitochondrial inner membrane by Opa1. The balance of long (L‐Opa1) and proteolytically cleaved short (S‐Opa1) isoforms is critical for efficient fusion. Oma1 is the predominant stress‐responsive protease for Opa1 processing. In neuronal cell models, we assessed Oma1 and Opa1 regulation during mitochondrial stress. In an immortalized mouse hippocampal neuron line (HT22), Oma1 was sensitive to mitochondrial membrane potential depolarization (rotenone, FCCP) and hyperpolarization (oligomycin). Further, oxidative stress was sufficient to increase Oma1 activity and necessary for depolarization‐induced proteolysis. We generated Oma1 knockout (KO) HT22 cells that displayed normal mitochondrial morphology and fusion capabilities. FCCP‐induced mitochondrial fragmentation was exacerbated in Oma1 KO cells. However, Oma1 KO cells were better equipped to perform restorative fusion after fragmentation, presumably due to preserved L‐Opa1. We extended our investigations to a combinatorial stress of neuronal oxygen–glucose deprivation and reoxygenation (OGD/R), where we found that Opa1 processing and Oma1 activation were initiated during OGD in an ROS‐dependent manner. These findings highlight a novel dependence of Oma1 on oxidative stress in response to depolarization. Further, we demonstrate contrasting fission/fusion roles for Oma1 in the acute response and recovery stages of mitochondrial stress. Collectively, our results add intersectionality and nuance to the previously proposed models of Oma1 activity.
First-Generation Low-Income Individuals in Medicine: A Scoping Review
Authors: Zheng Sijin , Brutus Nicholas , Rivera Alexis , O’Marr Jamieson M. , Gardezi Mursal , Grimshaw Alyssa A. , Malcolm Kenyer , Marcellon Roselande , Mason Hyacinth R. , Cavallo Jaime A. 
Published: September 2024

Abstract

Purpose
This comprehensive scoping review of the medical literature on first-generation low-income (FGLI) individuals in medicine aimed to synthesize the highest levels of evidence to inform medical education stakeholders.

Method
Database searches were conducted in Academic Search Premier, Education Research Premier, ERIC, Ovid MEDLINE, Ovid Embase, Professional Development Collection, PubMed, Scopus, Google Scholar, and Web of Science Core Collection from database inception through March 15, 2023. English-language articles on first-generation or low-income individuals in medicine from U.S. medical schools were included. Articles were evaluated for level of evidence and themes chosen.

Results
Database searches resulted in 27,075 citations, 247 of which qualified for data extraction. The articles were classified by evidence level: level I (n = 2), level II (n = 17), level III (n = 90), level IV (n = 78), and level V (n = 60). Publications reported on 9 major outcomes: exam performance (n = 108), medical school performance (n = 63), residency and fellowship performance (n = 7), honor society status (n = 12), leave of absence (n = 9), withdrawal, dismissal, and attrition (n = 20), medical education graduation (n = 37), career choice (n = 109), and intent to practice in disadvantaged and rural communities (n = 60). Compared with their peers, FGLI individuals had lower medical school and standardized exam scores, enrollment in national medical honor societies and multiple degree programs, and graduate medical education performance and higher rates of leaves of absence, incompletion of medical education, pursuing primary care and family medicine specialties, and intent to practice in underserved communities.

Conclusions
Despite an increase in the number of FGLI individuals in medicine, there remains significant opportunity to improve their inclusion and support. Multi-institutional, prospective, risk-adjusted, observational studies are required to determine how to best support FGLI individuals through all medical career stages.