bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic significance of plasma circulating tumor DNA fraction in patients with advanced sarcoma: A French Sarcoma Group study.
Authors: Taleb Sofiane , Brunet Maxime , Belcaid Laila , Bahleda Rastislav , Verret Benjamin , Le Cesne Axel , Peyraud Florent , spalato-Ceruso Mariella , Toulmonde Maud , Italiano Antoine 
Published: June 2024

11574 Background: The integration of liquid biopsies into clinical guidelines is revolutionizing the management of late-stage cancer. A notable advancement is the use of broad genomic analysis of circulating tumor DNA (ctDNA) for quantifying tumor fraction (TF). While TF's prognostic relevance in carcinomas has been explored, its significance in sarcomas remains unclear. Methods: This study involved patients with advanced sarcomas from two precision medicine studies (BIP, Institut Bergonié, Bordeaux, France; STING, Gustave Roussy, Villejuif, France) across two French Sarcoma Group sites. All participating patients underwent comprehensive genomic profiling with the FDA approved FoundationOne Liquid CDx assay. TF was measured using single-nucleotide polymorphism-based aneuploidy analysis as previously described (Reichert et al. 2023). Progression-free survival (PFS) and overall survival (OS) were assessed from treatment commencement (PFS) or the date of ctDNA profiling (OS) to disease progression, death, or last patient contact. Univariate analysis examined variables such as age, gender, tumor grade, metastatic sites, performance status (PS), and prior treatment lines. Results: 195 patients (103 males, 92 females) entered the study. The three most frequent histological subtypes were leiomyosarcomas, dedifferentiated liposarcomas, and undifferentiated pleiomorphic sarcomas. Median age was 56 (range 18-91). Thirty patients (15.4%) had high TF (≥ 10%). Among the 189 patients who underwent systemic treatment post-ctDNA profiling, elevated TF correlated with significantly poorer PFS (2.6 vs 4.3 months, p=0.018) and OS (6.7 vs 14.1 months, p=0.005). Multivariate analysis identified TF and ECOG performance status as independent predictors of OS. Conclusions: Plasma ctDNA TF is a practical and independent prognostic biomarker in advanced sarcoma patients. Its integration into treatment paradigms can facilitate precision therapeutic strategies tailored to individual tumor biology.
Identifying optimized assessment of nerve damage during chemotherapy.
Authors: Li Tiffany , Timmins Hannah C , Mahfouz Fawaz Mayez , Mizrahi David , Horvath Lisa , Harrison Michelle L. , Grimison Peter S. , Friedlander Michael , Marx Gavin M. , Boyle Frances M. , Wyld David , Henderson Robert , King Tracy , Baron-Hay Sally E. , Kiernan Matthew C , Rutherford Claudia , Goldstein David , Park Susanna B 
Published: June 2024

12016 Background: Chemotherapy-induced peripheral neurotoxicity (CIPN) is a significant and persisting toxicity of anticancer treatments, impacting dose delivery and quality of life. There is a lack of consensus on the optimal method of CIPN assessment in clinical settings. This study compared the validity and responsiveness of patient reported outcome measures (PROMs) against neurological, neurophysiological and sensory assessment approaches of CIPN. Methods: A multi-centre dual study design evaluated patients treated with neurotoxic chemotherapy across two cohorts: patients commencing treatment assessed prospectively and patients who completed treatment assessed cross-sectionally. CIPN was assessed via PROMs (EORTC-CIPN20, FACT/GOG-Ntx, PRO-CTCAE), neurological and neurophysiological assessment (Total Neuropathy Score, sural and tibial compound nerve amplitudes) and sensory functional measures (Grating orientation, Von Frey monofilament and 2-Point discrimination tasks). Convergent and known-groups validity were assessed cross-sectionally following treatment completion and responsiveness was evaluated prospectively during treatment. Neurological, neurophysiological, and sensory outcome measure scores were compared between high and low CIPN symptom reporters. Results: A total of 1,033 patients were recruited, incorporating 1,623 assessments. PROMs demonstrated superior ability to identify CIPN (convergent validity; α = 0.75-0.85, all P < 0.001), to discriminate between CIPN severity (known-groups validity; all P < 0.001) and to detect changes in CIPN development (responsiveness; Cohen’s d = 0.65-0.83) compared to neurological, neurophysiological and sensory assessment approaches. These other measures did not achieve threshold for convergent validity (α < 0.7). and did not demonstrate acceptable responsiveness (Cohen’s d < 0.5). Neurological, neurophysiological, and sensory outcome measures were significantly impaired in patients who were high CIPN symptom reporters compared to low (all P < 0.05). Conclusions: PROMs represent a valid method of CIPN assessment, with preferential measurement properties over other approaches to assessing neuropathy. Adoption of PROMs in clinical practice will allow for accurate representation and early recognition of CIPN, leading to reduced long term morbidity in this key long-term toxicity in cancer survivors.
Impact of protein-energy malnutrition on patients with breast cancer hospitalized for acute decompensated heart failure: Insight from the NIS database 2020.
Authors: Obomanu Elvis , Wattanachayakul Phuuwadith , Jones Colton , Arya Yajur , Syal Arshi , Byfield Karecia , Eidbo Sarah , Ratnani Akshay , Saowapa Sakditad , Polpichai Natchaya , Wannaphut Chalothorn , Casipit Carlo , Casipit Bruce Adrian , Mayo Ryan 
Published: June 2024

12030 Background: The breast cancer patient is at risk of acute decompensated heart failure (ADHF) and protein-energy malnutrition (PEM) either from the effects of chemoradiation or primary cancer. There have been several studies on patients with breast cancer and ADHF. However, the exact impact of concurrent PEM on patients with breast cancer admitted for ADHF is unclear. We aim to assess how PEM impacts breast cancer patients admitted with ADHF. Methods: We examined the 2020 US National Inpatient Sample (NIS) to explore how concurrent PEM affects breast cancer patients admitted for ADHF. Participants aged 18 and older were identified using relevant ICD-10 CM codes. A survey multivariate logistic and linear regression analysis was used to calculate the odds ratio (OR) for the outcomes of interest. Results: We identified 30,555 breast cancer patients with ADHF, with a mean age of 77±10 years; 99% were female. Caucasian accounted for 71.4%, followed by Black (17.5%), Mexican American (5%), and Asian (3%). Of these, 6.07% (1854/30,555) had a concurrent PEM diagnosis. In a survey multivariable regression model adjusting for patient and hospital factors, comorbid PEM was significantly associated with prolonged length of stay (β 2.09, 95% CI: 1.68–2.49, P <0.001), increased risk of in-hospital mortality (aOR 2.61, 95% CI: 1.60–4.29, P <0.001), increased risk of cardiogenic shock (aOR 3.17, 95% CI: 1.78–2.59, P< 0.001), anemia (aOR 1.43, 95% CI: 1.14 to 1.80, p 0.002), and total hospital charge $28,285 (95% CI: $21,743–34,827, P< 0.001). Adverse events such as respiratory failure (aOR 1.17, 95% CI 0.91 to 1.50, p 0.212) and DVT (aOR 1.15, 95% CI 0.40 to 3.31, p 0.802) were observed but did not reach statistical significance. Conclusions: Our study demonstrated that comorbid PEM among hospitalized breast cancer patients for ADHF is associated with increased risks of in-hospital mortality, anemia, cardiogenic shock, prolonged length of hospital stays, and total hospital charges. The study also highlights that nutritional status may be a useful prognostic marker in breast cancer patients who are at risk for various cardiovascular morbidities associated with cancer treatment and the primary disease. Additional longitudinal cohort studies are required to improve the understanding of this association.
Impact of palliative care on hospital length of stay and charges in hospitalized patients with cancer at end of life.
Authors: Hsieh Tien-Chan , Zou Guangchen 
Published: June 2024

12072 Background: Early palliative care has been shown to enhance the quality of life and survival for cancer patients. However, the economic implications of using palliative care in hospitalized cancer patients remain inconclusive. While palliative care can prevent aggressive interventions in end-of-life patients, it may also prolong hospitalization. Methods: This retrospective study used four years of National Inpatient Sample data (2016-2019) to explore the association between palliative care and hospital length of stay and charges among cancer patients aged 18 and above, hospitalized for at least 7 days and died. Hospital charges were divided by length of stay to derive the average daily charges. Continuous variables, length of stay and average daily charges, were standardized by subtracting means and dividing by standard deviations. We top-coded length of stay and average daily charges at the 99th percentile. Length of stay was also modeled into categories: 7-13, 14-20, 21-27, and 28+ days. A mixed-effects model with individual hospitals as a random effect was employed to account for potential variations in clinical practices and billing at the institutional level. Results: The study included 59,355 distinct cancer hospitalizations, totaling 296,775 weighted hospitalizations. Palliative care utilization was observed in 54.0%, and Do-not-resuscitate (DNR) status was noted in 57.9%. The observed palliative care use and DNR status were most prevalent in the 7-13 days group (56.6% and 61.3%) and least in the 28+ days group (46.9% and 48.8%). 85.2% didn’t receive cardiopulmonary resuscitation (CPR) and that rate was similar across all length of stay groups. In linear mixed-effects models using standardized length of stay, palliative use was associated with shorter length of stay (adjusted Odds Ratio {aOR} 0.89; confidence interval {CI} 0.88-0.90). After adjustment for covariates, DNR was also associated with shorter hospitalization (aOR: 0.81; CI: 0.80-0.82). Receiving CPR had lower adjusted risk for longer hospitalization (aOR: 0.94; CI: 0.93-0.95). In multivariate model, daily charges were inversely correlated to the length of stay (aOR: 0.92; CI: 0.92-0.92). When using average charges per day as dependent variable, palliative care use was associated with less charges (aOR: 0.83; CI: 0.83-0.84). DNR also showed a lower adjusted odds for hospital charges (aOR: 0.89; CI: 0.88-0.89). Receiving CPR had higher adjusted risk of higher charges (aOR: 1.23; CI: 1.22-1.24). Conclusions: The use of palliative care was associated with a shorter length of stay and lower hospital charges per day among cancer patients who died in the hospital after adjusting for covariates. Many of the 46% who died without palliative care could have benefitted from it. Interventions aimed at promoting palliative care services among inpatient cancer patients nearing the end of life might yield economic benefits.
A phase I/II study to evaluate the safety, pharmacokinetics, and efficacy of PRJ1-3024 in patients with advanced solid tumors.
Authors: Zhang Panpan , Qin Yanru , Gong Jifang , Wang Yongsheng , Yang Kunyu , Li Yongsheng , Dai Guanghai , Zhu Ji , Sha Sha , Tong Ming , Liao Xuebin , Shen Lin 
Published: June 2024

2590 Background: PRJ1-3024 is a small molecule hematopoietic progenitor kinase 1 (HPK1) inhibitor designed to potentiate T-cell function. It was demonstrated that HPK1 activity suppresses immune functions of a wide range of cells including cluster of differentiation CD4+, CD8+ T cells and dendritic cells (DCs), mediates T-cell dysfunction and is a potential therapeutic target for T-cell-based immunotherapies. These results strongly support inhibitor of HPK1 functioning as a potential cancer immunotherapy agent. Methods: This is a multicenter, open-label study. Primary objective of phase I study is to determine the maximum tolerated dose and recommended Phase 2 dose. Secondary objectives are to evaluate safety, PK, and efficacy of PRJ1-3024. It is dosed orally once daily. Dose-limiting toxicity (DLT) assessment to be completed after 24 days (from the first dose to the end of Cycle 1 continuous 21 medication days). Exploratory analysis of pharmacodynamic targets including multiple cytokines, SLP-76 phosphorylation, cfDNA and IgG typing. Results: As of Dec. 22, 2023, 30 patients were enrolled in 6 dose cohorts: 80, 160, 300, 320, 500, and 700mg. Median age was 59 years (range 36-69). Diagnoses were NSCLC (9), Melanoma (3), TNBC (3), Gastric Cancer (3), HNSCC (3), Esophagus Carcinoma (2), Colon Cancer (2), and other types (5). The most common TEAEs (in ≥2 pts) were diarrhea (12), vomiting (12), nausea (9), proteinuria (8), loss of appetite (6), etc. No DLT events, irAEs or treatment-related deaths occurred in all dose cohorts. 9 subjects reported SAEs, only 2 cases were evaluated to be probably related (6.7%), namely ‘myocardial ischemic’ and ‘acute kidney injury’. 1 melanoma subject achieved sustained PR, had been on treatment for more than 7 months up to now. 4 subjects achieved SD (1 NSCLC, 1 HNSCC, 2 TNBCs). PK and PD assessments will be released in due course. Conclusions: PRJ1-3024 is shown to be well tolerated in Chinese advanced solid tumor patients. Further safety and efficacy results would be presented at the conference. Clinical trial information: NCT05315167 .
A realistic neutrino mixing scheme arising from A4 symmetry
Authors: Dey Manash , Roy Subhankar 
Published: June 2024

Abstract
We propose a unique lepton mixing scheme and its association with an exact hierarchy-philic neutrino mass matrix texture in the light of Type-I+Type-II seesaw mechanism under the framework of

discrete flavour symmetry. The proposed model successfully predicts the normal ordering of neutrino masses and the two Majorana phases. Additionally, the analysis extends to the effective Majorana neutrino mass, in the context of neutrinoless double beta

.
Robustness to Dependency in Influence Maximization
Authors: Chen Louis L. , Lim Chee Chin , Padmanabhan Divya , Natarajan Karthik 
Published: June 2024

In this paper, we pursue a correlation-robust study of the influence maximization problem. Departing from the classic independent cascade model, we study a diffusion process adversarially adapted to the choice of seed set. More precisely, rather than the independent coupling of known individual edge probabilities, we now evaluate a seed set’s expected influence under all possible correlations, specifically, the one that presents the worst case. We find that the worst case expected influence can be efficiently computed, its NP-hard optimization done approximately [Formula: see text] with greedy construction, and we provide complete, efficient characterizations of the adversarial coupling, the random graph, and the random number of influenced nodes. But, most importantly, upon mixing the independent cascade with the worst case, we attain a tunable and more comprehensive model better suited for real-world diffusion phenomena than the independent cascade alone and without increased computational complexity. Extensions to the correlation-robust study of risk follow along with numerical experiments on network data sets with demonstration of how our models can be tuned. This paper was accepted by George Shanthikumar, data science. Funding: This work was supported by the Air Force Office of Scientific Research (Mathematical Optimization Program) under the grant: “Optimal Decision Making under Tight Performance Requirements in Adversarial and Uncertain Environments: Insight from Rockafellian Functions”. Supplemental Material: The online appendix and data files are available at https://doi.org/10.1287/mnsc.2021.03445 .
Does timely reporting of preoperative CT scans influence outcomes for patients following emergency laparotomy?
Authors: Ikram S , Mirtorabi N , Ali D , Aain H , Naumann DN , Dilworth M 
Published: June 2024

Introduction Timely preoperative computed tomography (CT) scans are important for patients requiring emergency laparotomy. United Kingdom guidelines state that a CT scan should be reported within 1h for ‘critical’ patients (will alter management at the time) and within 12h for ‘urgent’ patients (will alter management but not necessarily that day). Methods An observational study included patients who were added to the National Emergency Laparotomy Audit (NELA) at a National Health Service trust from 2014 to 2021. The association of compliance with timings guidance and mortality was investigated. Multivariable logistic regression was used to determine the odds ratio of adherence to guidelines according to age, gender, night time admission, American Society of Anesthesiology (ASA) score, NELA mortality risk and category of scan. Further models determined the influence of adherence to guidelines on mortality, also adjusted for these variables. Results There were 1,299 patients (48% ‘critical’ and 52% ‘urgent’ CT scans). Only 360/1,299 (28%) of scans were undertaken with adherence to the timing guidelines. Critical scans were less likely to adhere to guidelines. Although univariable analysis suggested that adherence to guidelines was associated with reduced mortality, this was not the case in the multivariable model: only age, ASA and NELA mortality risk remained significantly associated with mortality. Conclusions A minority of patients met the recommended preoperative CT report timings, and this was less likely for scans designated ‘critical’. This did not appear to affect mortality when adjusted for key variables of risk. This illustrates the phenomenon of guideline adherence appearing to affect patient outcomes as a product of selection bias rather than causality.
Stress and sleep deprivation-related biomarkers in saliva in patients with retinitis pigmentosa
Authors: Mateos-Olivares Milagros , Pastor-Idoate Salvador , Martín-Vallejo Javier , García-Vazquez Cristina , Pastor José Carlos , Usategui-Martín Ricardo , Sobas Eva María 
Published: June 2024

Purpose
Patients with Retinitis Pigmentosa (RP) commonly experience sleep-related issues and are susceptible to stress. Moreover, variatiaons in their vision are often linked to anxiety, stress and drowsiness, indicating that stress and sleep deprivation lead to a decline in vision, and vision improves when both are mitigated. The objective of this study was to investigate the utility of salivary biomarkers as biochemical indicators of anxiety and sleep deprivation in RP patients.

Methods
Seventy-eight RP patients and 34 healthy controls were included in this observational study. Anxiety and sleep-quality questionnaires, a complete ophthalmological exam for severity grading and, the collection of salivary samples from participants were assessed for participants. The activity of biomarkers was estimated by ELISA, and statistical analysis was performed to determine associations between the parameters. Associations between underlying psychological factors, grade of disease severity, and biomarkers activity were also examined.

Results
Fifty-two (67%) of patients had a severe RP, and 26 (33%) had a mild-moderate grade. Fifty-eight (58,9%) patients reported severe levels of anxiety and 18 (23.,1%) a high level. Forty-six (59%) patients obtained pathological values in sleep-quality questionaries and 43 (55.1%) in sleepiness.
Patients with RP exhibited significant differences in testosterone, cortisol, sTNFαRII, sIgA and melatonin as compared to controls and patients with a mild-moderate and advanced stage of disease showed greater differences. In covariate analysis, patients with a severe anxiety level also showed greater differences in mean salivary cortisol, sTNFαRII and melatonin and male patients showed lower IgA levels than female.

Conclusions
The present findings suggest that salivary biomarkers could be suitable non-invasive biochemical markers for the objective assessment of sleep deprivation and anxiety in RP patients. Further research is needed to characterize the effects of untreated negative psychological states and sleep deprivation on increased variability of vision and disease progression, if any.
Assessment of knowledge, attitudes, and practices among community pharmacists in Lahore regarding antibiotic dispensing without prescription: A cross-sectional study
Authors: Nabeel Muhammad , Ali Khubaib , Sarwar Muhammad Rehan , Waheed Imran 
Published: June 2024

Objectives
The irrational dispensing practices are responsible for antibiotic abuse and the spread of antibiotic resistance. Thus, the present study aims to evaluate the knowledge, attitudes, and practices of community pharmacists (CPs) regarding dispensing antibiotics without prescription (DAwP).

Method
A descriptive, cross-sectional study was conducted between March 1, 2023, and March 31, 2023, in community pharmacy settings of Lahore, Pakistan. A self-administered and pretested questionnaire was used for the data collection. Logistic regression analysis was used to determine the factors associated with the practices of community pharmacists. Data were analyzed using SPSS (version 26) and MS Office (2016).

Results
Among 359 respondents, many strongly agreed/agreed with the statements "DAwP is contributing to the development of antimicrobial resistance" (83%, n = 298) and "Antibiotic resistance has become a public health issue" (81.9%, n = 249). Overall, most of the community pharmacists claimed that the unwillingness of patients to visit physicians for non-serious infections (75.2%, n = 270) and good knowledge of pharmacists about the use of antibiotics (51%, n = 183) were the most common reasons attributable to dispensing of antibiotics without prescription. Cephalosporin (n = 260, 72.4%), penicillin (n = 254, 70.8%), and tetracyclines (n = 170, 47.4%) were the most commonly dispensed classes of antibiotics without prescription due to cold, flu and diarrhea. Most community pharmacists never/sometimes warn patients about the potential side effects of medicines (79.1%, n = 284). Logistic regression analysis revealed that community pharmacists 31–40 years of age (OR = 0.568, 95%CI = 0.348–0.927, p-value = 0.024) were significantly less associated with poor practices of dispensing antibiotics without prescription (DAwP) while those who were ’Managers’ (OR = 4.222, 95%CI = 2.542–7.011, p-value = <0.001), had 3–5 years of experience (OR = 2.241, 95%CI = 1.183–4.243, p-value = 0.013), dispensed ≤25 antibiotics per day (OR = 12.375, 95%CI = 5.177–29.583, p-value = <0.001), were more likely to be associated with poor practices of dispensing of antibiotics without prescription.

Conclusion
The community pharmacists had adequate knowledge, positive attitudes, and poor practices towards DAwP. Demographical factors such as age, job status, and work experience were the determinants of community pharmacists’ practices towards dispensing antibiotics without prescription (DAwP). Hence, a multifaceted approach, including educational interventions, is needed to reduce the dispensing of antibiotics without prescription (DAwP).