bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aurora Kinase A inhibition enhances DNA damage and tumor cell death with 131I-MIBG therapy in high-risk neuroblastoma
Authors: Kumar Prerna , Koach Jessica , Nekritz Erin , Mukherjee Sucheta , Braun Benjamin S. , DuBois Steven G. , Nasholm Nicole , Haas-Kogan Daphne , Matthay Katherine K. , Weiss William A. , Gustafson Clay , Seo Youngho 
Published: June 2024

Abstract
Background
Neuroblastoma is the most common extra-cranial pediatric solid tumor. 131I-metaiodobenzylguanidine (MIBG) is a targeted radiopharmaceutical highly specific for neuroblastoma tumors, providing potent radiotherapy to widely metastatic disease. Aurora kinase A (AURKA) plays a role in mitosis and stabilization of the MYCN protein in neuroblastoma. We aimed to study the impact of AURKA inhibitors on DNA damage and tumor cell death in combination with 131I-MIBG therapy in a pre-clinical model of high-risk neuroblastoma.

Results
Using an in vivo model of high-risk neuroblastoma, we demonstrated a marked combinatorial effect of 131I-MIBG and alisertib on tumor growth. In MYCN amplified cell lines, the combination of radiation and an AURKA A inhibitor increased DNA damage and apoptosis and decreased MYCN protein levels.

Conclusion
The combination of AURKA inhibition with 131I-MIBG treatment is active in resistant neuroblastoma models.
New improved radiometabolite analysis method for [18F]FTHA from human plasma: a test-retest study with postprandial and fasting state
Authors: Aarnio Richard , Kirjavainen Anna , Rajander Johan , Forsback Sarita , Kalliokoski Kari , Nuutila Pirjo , Milicevic Zvonko , Coskun Tamer , Haupt Axel , Laitinen Iina , Haaparanta-Solin Merja 
Published: June 2024

Abstract
Background
Fatty acid uptake can be measured using PET and 14-(R,S)‐[18F]fluoro‐6‐thia‐heptadecanoic acid ([18F]FTHA). However, the relatively rapid rate of [18F]FTHA metabolism significantly affects kinetic modeling of tissue uptake. Thus, there is a need for accurate chromatographic methods to analyze the unmetabolized [18F]FTHA (parent fraction). Here we present a new radiometabolite analysis (RMA) method, with comparison to a previous method for parent fraction analysis, and its use in a test-retest clinical study under fasting and postprandial conditions. We developed a new thin-layer chromatography (TLC) RMA method for analysis of [18F]FTHA parent fraction and its radiometabolites from plasma, by testing stationary phases and eluent combinations. Next, we analyzed [18F]FTHA, its radiometabolites, and plasma radioactivity from subjects participating in a clinical study. A total of 17 obese or overweight participants were dosed with [18F]FTHA twice under fasting, and twice under postprandial conditions and plasma samples were obtained between 14 min (mean of first sample) and 72 min (mean of last sample) post-injection. Aliquots of 70 plasma samples were analyzed using both methods, enabling head-to-head comparisons. We performed test-retest and group comparisons of the parent fraction and plasma radioactivity.

Results
The new TLC method separated seven [18F]FTHA radiometabolite peaks, while the previous method separated three. The new method revealed at least one radiometabolite that was not previously separable from [18F]FTHA. From the plasma samples, the mean parent fraction value was on average 7.2 percentage points lower with the new method, compared to the previous method. Repeated [18F]FTHA investigations on the same subject revealed reproducible plasma SUV and parent fractions, with different kinetics between the fasted and postprandial conditions.

Conclusions
The newly developed improved radio-TLC method for [18F]FTHA RMA enables accurate parent fraction correction, which is required to obtain quantitative data for modelling [18F]FTHA PET data. Our test-retest study of fasted and postprandial conditions showed robust reproducibility, and revealed clear differences in the [18F]FTHA metabolic rate under different study settings.

Trial registration
EudraCT No: 2020-005211-48, 04Feb2021; and Clinical Trials registry NCT05132335, 29Oct2021, URL: https://classic.clinicaltrials.gov/ct2/show/NCT05132335.
Development and application of a risk nomogram for the prediction of risk of carbapenem-resistant Acinetobacter baumannii infections in neuro-intensive care unit: a mixed method study
Authors: Li Yuping , Gao Xianru , Diao Haiqing , Shi Tian , Zhang Jingyue , Liu Yuting , Zeng Qingping , Ding JiaLi , Chen Juan , Yang Kai , Ma Qiang , Liu Xiaoguang , Yu Hailong , Lu Guangyu 
Published: June 2024

Abstract
Objective
This study aimed to develop and apply a nomogram with good accuracy to predict the risk of CRAB infections in neuro-critically ill patients. In addition, the difficulties and expectations of application such a tool in clinical practice was investigated.

Methods
A mixed methods sequential explanatory study design was utilized. We first conducted a retrospective study to identify the risk factors for the development of CRAB infections in neuro-critically ill patients; and further develop and validate a nomogram predictive model. Then, based on the developed predictive tool, medical staff in the neuro-ICU were received an in-depth interview to investigate their opinions and barriers in using the prediction tool during clinical practice. The model development and validation is carried out by R. The transcripts of the interviews were analyzed by Maxqda.

Results
In our cohort, the occurrence of CRAB infections was 8.63% (47/544). Multivariate regression analysis showed that the length of neuro-ICU stay, male, diabetes, low red blood cell (RBC) count, high levels of procalcitonin (PCT), and number of antibiotics ≥ 2 were independent risk factors for CRAB infections in neuro-ICU patients. Our nomogram model demonstrated a good calibration and discrimination in both training and validation sets, with AUC values of 0.816 and 0.875. Additionally, the model demonstrated good clinical utility. The significant barriers identified in the interview include “skepticism about the accuracy of the model”, “delay in early prediction by the indicator of length of neuro-ICU stay”, and “lack of a proper protocol for clinical application”.

Conclusions
We established and validated a nomogram incorporating six easily accessed indicators during clinical practice (the length of neuro-ICU stay, male, diabetes, RBC, PCT level, and the number of antibiotics used) to predict the risk of CRAB infections in neuro-ICU patients. Medical staff are generally interested in using the tool to predict the risk of CRAB, however delivering clinical prediction tools in routine clinical practice remains challenging.
Seabirds show foraging site and route fidelity but demonstrate flexibility in response to local information
Authors: Regan Charlotte E. , Bogdanova Maria I. , Newell Mark , Gunn Carrie , Wanless Sarah , Harris Mike P. , Lopez Samuel Langlois , Benninghaus Ella , Bolton Mark , Daunt Francis , Searle Kate R. 
Published: June 2024

Abstract
Background
Fidelity to a given foraging location or route may be beneficial when environmental conditions are predictable but costly if conditions deteriorate or become unpredictable. Understanding the magnitude of fidelity displayed by different species and the processes that drive or erode it is therefore vital for understanding how fidelity may shape the demographic consequences of anthropogenic change. In particular, understanding the information that individuals may use to adjust their fidelity will facilitate improved predictions of how fidelity may change as environments change and the extent to which it will buffer individuals against such changes.

Methods
We used movement data collected during the breeding season across eight years for common guillemots, Atlantic puffins, razorbills, and black-legged kittiwakes breeding on the Isle of May, Scotland to understand: (1) whether foraging site/route fidelity occurred within and between years, (2) whether the degree of fidelity between trips was predicted by personal foraging effort, and (3) whether different individuals made more similar trips when they overlapped in time at the colony prior to departure and/or when out at sea suggesting the use of the same local environmental cues or information on the decisions made by con- and heterospecifics.

Results
All species exhibited site and route fidelity both within- and between-years, and fidelity between trips in guillemots and razorbills was related to metrics of foraging effort, suggesting they adjust fidelity to their personal foraging experience. We also found evidence that individuals used local environmental cues of prey location or availability and/or information gained by observing conspecifics when choosing foraging routes, particularly in puffins, where trips of individuals that overlapped temporally at the colony or out at sea were more similar.

Conclusions
The fidelity shown by these seabird species has the potential to put them at greater risk in the face of environmental change by driving individuals to continue using areas being degraded by anthropogenic pressures. However, our results suggest that individuals show some flexibility in their fidelity, which may promote resilience under environmental change. The benefits of this flexibility are likely to depend on numerous factors, including the rapidity and spatial scale of environmental change and the reliability of the information individuals use to choose foraging sites or routes, thus highlighting the need to better understand how organisms combine cues, prior experience, and other sources of information to make movement decisions.
The mRNA surveillance factor Pelo restricts rice virus propagation in insect vectors and host plants
Authors: Sun Xinyan , Guan Heran , Wei Taiyun , Jia Dongsheng 
Published: June 2024

AbstractMany devastating plant viruses are transmitted by insect vectors among plant hosts in a persistent-propagative manner. Pelota (Pelo) is an evolutionarily conserved protein involved in the mRNA surveillance system. In this study, it was found that the accumulation of Pelo proteins are slightly decreased during the propagation of the fijivirus southern rice black-streaked dwarf virus (SRBSDV) in rice and transmission vector planthopper (Sogatella furcifera). The tubular protein P7-1 encoded by SRBSDV interacted with Pelo of rice or planthopper vector. Overexpression or knockdown of Pelo expression inhibits the formation of P7-1 tubules in insect cells, further exerting antiviral activity. Furthermore, overexpression or knockout of Pelo expression in transgenic rice plants also inhibits the effective propagation of SRBSDV as well as two other rice viruses of different families. The slight reduction of Pelo accumulation during SRBSDV propagation in rice and insect vectors would avoid Pelo-mediated excessive inhibition of P7-1 tubule formation, ensuring effective virus propagation. Our findings provide insights into how the up- or down-regulated expression of Pelo in rice hosts and insect vectors elevate their resistance to rice viruses.
Final results of a randomized phase II/III study comparing perioperative adriamycin plus ifosfamide and gemcitabine plus docetaxel for high-grade soft tissue sarcomas: Japan Clinical Oncology Group study JCOG1306.
Authors: Tanaka Kazuhiro , Machida Ryunosuke , Endo Makoto , Kawai Akira , Nakayama Robert , Tsukushi Satoshi , Asanuma Kunihiro , Hiraga Hiroaki , Hiraoka Koji , Yoshida Shinichiro , Yonemoto Tsukasa , Imanishi Jungo , Katagiri Hirohisa , Nishida Yoshihiro , Nagano Akihito , Sekino Yuta , Fukuda Haruhiko , Ozaki Toshifumi , Iwamoto Yukihide ,   JCOG Bone and Soft Tissue Tumor Study Group
Published: June 2024

11503 Background: We have previously reported long-term follow-up results of the favorable efficacy of perioperative chemotherapy with adriamycin plus ifosfamide (AI) for high-grade soft tissue sarcomas (STS) (JCOG0304). We have also reported the results of the second interim analysis of a phase II/III trial to confirm the non-inferiority of perioperative gemcitabine plus docetaxel (GD) to AI for high-grade STS (JCOG1306) in 2020 ASCO Annual Meeting. This study was terminated at the preplanned second interim analysis based on the point estimate of hazard ratio (HR) being above the pre-specified allowable HR of 1.61. The estimated 2-year overall survival (OS) was 94.3% (95% confidence interval (CI) 83.4–98.1%) in AI and 91.6% (80.9–96.4%) in GD (HR 2.55, 95% CI 0.80–8.14) in the analysis. We herein report the final results of JCOG1306 at 5-year follow-up. Methods: Patients with operable, FNCLCC grade 2/3 STS primary tumor (T2bN0M0 or anyTN1M0, AJCC 7th edition) or first local recurrent tumor in the extremities or trunk were randomized to AI or GD. Chemotherapy consisted of adriamycin 60 mg/m2 plus ifosfamide 10 g/m2 for AI or gemcitabine 1,800 mg/m2 plus docetaxel 70 mg/m2 for GD. The treatments were repeated for 3 courses preoperatively and 2 courses postoperatively in a 3-week interval. The primary endpoint in phase III part was OS. Planned sample size was 140 with a one-sided alpha of 0.1, power of 0.7 and a non-inferiority margin of 8% at 3-year OS (HR of 1.61), assuming 3-year OS of AI to be 85% and that of GD as 87%. Results: A total of 143 patients were enrolled between February 2014 and September 2018, and 5-year follow-up has finished in September 2023. Seventy and 73 patients were assigned to AI and GD, respectively, and included in the efficacy analysis. At the final analysis with a median follow-up of 6.0 years, the estimated 5-year OS was 90.0% (95% CI 80.1–95.1%) in AI and 76.1% (64.5–84.4%) in GD (HR 2.67, 95% CI 1.23–5.80). The estimated 5-year progression-free survival was 65.2% (95% CI: 52.7–75.2%) in AI and 57.4% (45.2–67.8%) in GD (HR: 1.33, 95% CI 0.81–2.18). At the 5-year follow-up analysis, there were no treatment-related deaths in both arms. Conclusions: The results of the second interim analysis were confirmed in the final analysis after five-year follow-up, i.e., non-inferiority of GD to AI in terms of OS could not be confirmed. In the perioperative chemotherapy for high-grade STS in the extremities and trunk, AI remains the standard regimen. Clinical trial information: jRCTs031180003 .
Functional impairments, fatigue, and pain in newly diagnosed solid-tumors: Retrospective path analysis.
Authors: Beeler Dori Michelle , Boselli Danielle , Meadors Patrick L. , Walsh Declan 
Published: June 2024

12066 Background: A large patient cohort study found functional impairments (FI) are associated with cancer-related fatigue (CRF). This was before anti-cancer treatment for solid tumors. Another found functional limitations increased with self-reported pain severity. We hypothesize that both (a) a direct association between pain and CRF and (b) an indirect association between the symptoms through a mediation pathway involving FI may exist. Our retrospective, single-institutional study evaluated this model. Methods: We sourced Electronic Distress Screening (EDS) and Cancer Registry databases (Jan 2017 - Jan 2022). Patients identified were ≥18 years old and completed EDS within two (±2) weeks of a solid tumor diagnosis and before any anti-cancer therapy. Three EDS questions assessed FI with a two-week recall: 1) “How well have you managed your daily life?”; 2) “Has your physical health kept you from doing things like household chores or climbing stairs?”; 3) “Do you have limited movement in any body part?”. Pain and CRF were assessed on a numerical rating scale [0 (none) to 10 (worst possible)]. Structural equation modeling tested the multiple mediation model. The 95% confidence intervals of the estimated total and FI domain-specific indirect effects, the effects of pain on CRF working through FI, were assessed to exclude zero. Results: N=4326. Median age = 63 years (range 18 - 97); 69% female and 78% White. The commonest tumor site groups were breast (30%), upper GI (17%), and gynecologic (16%); 21% had Stage 4 disease. Median CRF was 4 (range 0-10); 57% had clinically significant CRF (fatigue ≥4). Median pain was 3 (range 0-10); 51% had clinically significant pain (pain ≥3). A significant minority had FI. N=753 (17%) had either “very poor” or “fairly poor” management of day-to-day life. N=778 (18%) had “a lot” of difficulty in performing chores. N=1252 (29%) had limited movement of any body part. FI partially mediated the pain/CRF relationship (indirect effect (IEtotal)=0.25, 95% CI 0.24-0.27). Two mediators had statistically significant contributions to the total indirect effect: management of daily life (IEmanage=0.12, 95% CI 0.11-0.13); and difficulty in performing chores (IEchores=0.13, 95% CI 0.11-0.14). The limited movement of any body part did not impact the pain/CRF relationship (IEmovement=-0.01, 95% CI -0.01-0.01). Conclusions: Most patients had clinically significant pain and CRF at diagnosis. A significant minority had FI at diagnosis. FI partially mediated the direct relationship between pain/CRF severity. This helps us understand that FI accounts for some of the relationship between pain and CRF. It is insufficient to conduct symptom assessments without also evaluating FI before treatment or at diagnosis.
Fertility and Pregnancy Outcomes in Primary Hyperparathyroidism: Observations From a Large Insured Population
Authors: Sant Vivek R , Zhou Hui , Zhou Mengnan M , Adams Annette L , Ryan Denison S , Case Samuel K , Seo Young-Ji , Haigh Philip I , Janzen Carla , Yeh Michael W 
Published: June 2024

Abstract

Context
Primary hyperparathyroidism (PHPT) has initially been implicated in adverse maternal and neonatal outcomes, while subsequent population studies have failed to show an association.

Objective
This work aimed to compare maternal, pregnancy, and neonatal outcomes in patients with and without PHPT.

Methods
A retrospective matched-cohort study (2005-2020) was conducted at an integrated health-care delivery system in Southern California. Women aged 18 to 44 years were included. Patients with a biochemical diagnosis of PHPT were matched 1:3 with eucalcemic controls (non-PHPT). Main outcome measures included achievement of pregnancy, pregnancy outcomes (including rates of abortion, maternal complications), and neonatal outcomes (including hypocalcemia, need for intensive care).

Results
The cohort comprised 386 women with PHPT and 1158 age-matched controls. Pregnancy rates between PHPT and control groups were similar (10.6% vs 12.8%). The adjusted rate ratio of pregnancy was 0.89 (95% CI, 0.64-1.24) (PHPT vs non-PHPT). Twenty-nine pregnancies occurred in women with coexisting PHPT and 191 pregnancies occurred in controls, resulting in 23 (79.3%) and 168 (88.0%) live births, respectively (P = .023). Neonatal outcomes were similar. Live birth rates were similar (86.4%, 80%, 79.2%) for those undergoing parathyroidectomy prior (n = 22), during (n = 5), or after pregnancy/never (n = 24). Among patients who underwent parathyroidectomy during pregnancy, no spontaneous abortions occurred in women entering pregnancy with peak calcium less than 11.5 mg/dL (2.9 mmol/L).

Conclusion
We observed no difference in pregnancy rates between women with or without PHPT. Performing parathyroidectomy before pregnancy or during the second trimester appears to be a safe and successful strategy, and adherence to this strategy may be most critical for patients with higher calcium levels (≥11.5 mg/dL [2.9 mmol/L]).
Identifying and Treating Those at Risk: Disparities in Rapid Relapse Among TNBC Patients in the National Cancer Database
Authors: Rahurkar Saurabh , Jonnalagadda Pallavi , Stover Daniel , Andersen Barbara , Handley Demond , Elsaid Mohamed I. , Chen J. C. , Obeng-Gyasi Samilia 
Published: June 2024

Abstract
Purpose
This study was designed to characterize features of rapid relapse TNBC (rrTNBC), an aggressive, poor prognosis breast cancer subset using the National Cancer Database (NCDB).

Methods
Patients diagnosed with TNBC between 2010 and 2019 within NCDB were included in analyses. rrTNBC was defined as all-cause mortality ≤24 months from diagnosis. Patient demographic, tumor, and treatment association with rrTNBC were evaluated in univariate, bivariate analyses, and multiple logistic regression models. Two-part models are used to compare receipt of treatment (i.e., receipt of both chemotherapy and breast surgery) versus not in its relationship with rrTNBC.

Results
Overall, 14.5% of patients were categorized as rrTNBC. Age older than 75 years (−41.3%), Black race (−1.4%), Medicare (−2.6%), and Charlson-Deyo score ≥2 (−4.9%) were associated with a lower probability of receiving both chemotherapy and breast surgery. Not receiving both treatments (vs. receiving both chemotherapy and breast surgery) was associated with a two-to-three-fold higher probability of rrTNBC among patients aged older than 75 years (16.6% vs. 6%), having Medicare (3.6% vs. 1.6%), and Charlson-Deyo score ≥2 (16.6% vs. 5.9%).

Conclusions
Age, insurance, and comorbidity were related to a lower likelihood of treatment; yet receiving treatment reduced the risk of rrTNBC threefold for each. These findings might be valuable to inform clinical care delivery, as well as future research that examines treatment protocols among diverse patients.
How to treat androgenetic alopecia – the most common form of hair loss. A review
Authors: Stradczuk Monika , Mazurek Łukasz , Rękas Barbara , Mazurek Wojciech , Piętak Mateusz , Kruczyk Barbara , Kopacz Wojciech , Olędzka Joanna , Czach Zuzanna , Bachurska Dominika 
Published: June 2024

Introduction and purposeAndrogenetic alopecia (AGA) is one of the most common causes of baldness worldwide. It affects up to 80% of men by the age of 70 and up to 40% of postmenopausal women. In AGA etiology and pathogenesis, the three essential components play a key role - genetic inheritance, patient age and hormonal effects of androgens. In the following review, we have described the available FDA-approved and off-label treatments for AGA, along with their efficacy and potential side effects that should always be considered to prevent treatment discontinuation by the patients.The state of knowledgeThe pathogenesis of AGA is based on inherited dihydrotestosterone (DHT) sensitivity in the scalp skin, which leads to progressive hair loss. The literature documents the effectiveness of several treatments with different mechanisms of action in AGA therapy, but only topical minoxidil and oral finasteride gained FDA approval so far. Minoxidil acts by the blood vessels dilatation that increases the flow of oxygenated and growth factor-enriched blood to the hair follicles in the skin. 5-alpha reductase inhibitors, such as finasteride and dutasteride are another threapeutic option. Thy act by the inhibition of 5-alpha reductase, the enzyme which converts testosterone to DHT - the main causative agent of androgenetic alopecia. Recently, topical applications of minoxidil and finasterid, along with completely new emerging treatments for androgenetic alopecia are gaining popularity among doctors and patients. SummaryThis review describes current treatments for AGA, considering their efficacy, optimal doses, and the most common side effects. An important fact to emphasise is that androgenetic alopecia is based on a genetic predisposition, and treatment requires long-term use. For this reason, when choosing a medication, it is essential to cooperate with the patient and combine different therapeutic methods to achieve the desirable outcome while avoiding adverse reactions.