bluuebunny/crossref_metadata_2025_split huggingface dataset:
Revealing heterogeneity in chronic lymphocytic leukemia: AI-driven insights into aggressive and indolent disease subtypes.
Authors: Qorri Bessi , Geraci Joseph , Tsay Mike , Cumbaa Christian , Alphs Larry , Pani Luca 
Published: July 2024

e19029 Background: Chronic lymphocytic leukemia (CLL) exhibits a broad spectrum of clinical behaviors, from indolent courses requiring minimal intervention to aggressive forms demanding immediate treatment. The underlying heterogeneity of CLL poses significant challenges in predicting disease progression and tailoring patient-specific therapeutic strategies. Leveraging advanced and novel artificial intelligence (AI) and machine learning (ML) methodologies, our study aims to dissect the complexity of CLL, focusing on the identification and characterization of biomarkers that differentiate aggressive and indolent disease forms. Methods: The NetraAI is a priorietaryAI/ML system that is also being utilized in a research collaboration at a leading American oncology institute (not disclosed) that integrates machine intelligence, augmented intelligence, and an agent that interacts with AI-derived patient representations. This system was designed to learn from datasets with a small number of samples and many independent variables. This system operates by generating hypotheses in the form of interactive representations of patient populations that reveal heterogeneity along with statistically significant driving factors. Finally, an automated agent called AutoPlay interacts with these representations and generates an accounting of all variables, subpopulations of samples, and it also generates a human readable perspective on what was discovered by the data set. Results: We applied the NetraAI to a CLL dataset and used it to refine the analysis and interpretation of the corresponding transcriptomic data (GSE39411). Significantly lower levels of FADS3, GSDME, LPL, IMMT, NMB, and AEBP1 and higher expressions of COBLL1, P2RY1R, PDE8A, SYNE2, and FCRL3 were identified as hallmarks of indolent CLL, suggesting these markers could inform less aggressive disease management strategies. Furthermore, within a total of 104 CLL samples, we uncovered two distinct subpopulations within aggressive CLL, delineated by unique genetic markers. Group A, encompassing 31 aggressive CLL samples is predominantly characterized by the expression of lipoprotein lipase (LPL), while Group B, comprising 22/23 aggressive samples, is characterized by ZBTB20 and SYNE2. Our poster will also provide glimpses into a more refined heterogeneity that emerged from the analysis. Our results not only underscore the heterogeneity within aggressive CLL, but also highlights the potential for these markers to guide prognostic assessments and therapeutic decisions. Conclusions: This study not only advances our understanding of CLL heterogeneity, but also sets the stage for the development of more personalized and effective treatment modalities. By identifying drivers of disease aggression and indolence, we pave the way for targeted therapies that could significantly improve patient outcomes in CLL.
A phase 1, multi-center, safety, feasibility, and preliminary efficacy study evaluating a single dose of UNO101 in relapsed or refractory, unresectable, primary, or metastatic cutaneous and subcutaneous malignancies.
Authors: Dirbas Frederick M. , Meirovitz Amichay , Greenberg David , Dekel Edith , Choy Gavin S. , Monson Jedidiah 
Published: July 2024

TPS2686 Background: Tumor ablation is a minimally invasive technique commonly used to treat solid tumors in the liver, kidney, bone, and lung and is usually based on thermal and nonthermal approaches. Local and in-situ tumor ablation methods demonstrate enhanced anti-tumor immune responses resulting in the destruction of residual malignant cells in primary tumors and distant metastases. Nitric oxide (NO) is a colorless gas and a short-lived free radical. It is a ubiquitous, endogenously generated gas implicated in the homeostatic regulation of physiological processes. Preclinical studies evaluating the effect of high concentration exogenously administered NO demonstrated its anti-cancer properties and suggested that it may serve as a potent tumoricidal agent. We have previously shown that treating mouse colon carcinoma (CT26) tumor-bearing mice with ultra-high concentrations of nitric oxide (UNO101) upregulates innate and adaptive immune cells both locally and systemically. Beyond Cancer is currently conducting a first-in-human, first-in-class, Phase 1 safety, feasibility, and preliminary efficacy clinical study of UNO101 at multiple institutions in Israel. Methods: The study is a 2-part Phase 1 trial with a Dose Escalation and a Dose Expansion portion (NCT05351502). A conventional 3+3 dose escalation will evaluate three cohorts of UNO101 single dose: 25,000, 50,000 and 100,000 parts per million (PPM) delivered intratumorally over 5 minutes in subjects with an ECOG PS of 0–3, at least 3 months of life expectancy, with relapsed or refractory unresectable primary or metastatic cutaneous and subcutaneous measurable solid tumors being eligible for enrollment. Upon determination of the maximum tolerated dose or biological effective dose, whichever occurs first, the proposed recommended Phase 2 dose will be further evaluated in the Dose Expansion portion of the study. RECIST version 1.1 and iRECIST will be utilized to assess the rate of malignant tumor response after UNO administration and toxicity will be graded per NCI CTCAE version 5.0. Evaluation of response per itRECIST will also be explored. Up to thirty-eight enrolled subjects are anticipated. Cohort 1, 25,000 PPM have been completed without a reported DLT. Enrollment to Cohort 2, 50,000 PPM, began in January 2024. This study was approved by Israel Ministry of Health (IMOH) as well as the participating institution’s Ethics Board. Written informed consent was obtained for all enrolled subjects and a copy of the written consent is available for review. Clinical trial information: NCT05351502 .
Dynamic Response of Musclin, a Myokine, to Aerobic Exercise and Its Interplay With Natriuretic Peptides and Receptor C
Authors: Nam Ji Sun , Cho Eun-Suk , Kwon Yu Rim , Park Jong Suk , Kim YuSik 
Published: July 2024

Abstract

Objectives
Musclin, recently identified as a myokine, has been recognized for its physiological significance in potentiating the functional properties of natrieutic peptides (NPs) through competitive inhibition of their clearance receptor, natrieutic peptide receptor C (NPR-C). This study, for the first time in the literature, investigated the dynamic response of musclin during and after aerobic exercise in humans, exploring its potential as a myokine and its interaction with NPs and NPR-C in the context of exercise-induced metabolic responses.

Methods
Twenty-one inactive young males participated, and we assessed changes in serum levels of musclin, atrial natriuretic peptide (ANP), brain natriuretic peptide, epinephrine, and glycerol as indicative of lipid mobilization, during and after moderate-intensity aerobic exercise. Furthermore, we evaluated the gene expression of NPR-C in subcutaneous fat biopsies.

Results
Serum musclin levels increased significantly during aerobic exercise, followed by a decline during recovery, remaining elevated compared to baseline. Significant correlations were found between musclin responses and lean body mass (LBM), indicating its regulation by skeletal muscle mass and exercise. Exercise-induced changes in musclin positively correlated with those of ANP, potentially preventing ANP degradation. Additionally, a potential interplay between NPR-C expression and musclin dynamics on ANP was suggested. However, musclin's influence on lipid mobilization was not predominant when considering other lipolytic factors during exercise.

Discussion
Musclin's classification as a myokine is supported by its response to aerobic exercise and its association with LBM. Additionally, its interactions with NPR-C and NPs suggest its physiological relevance and potential clinical implications.
Understanding Barriers to Guideline-Concordant Treatment in Foregut Cancer: From Data to Solutions
Authors: Fonseca Annabelle L. , Ahmad Rida , Amin Krisha , Tripathi Manish , Abdalla Ahmed , Hearld Larry , Bhatia Smita , Heslin Martin J. 
Published: July 2024

Abstract
Background
A large proportion of patients with foregut cancers do not receive guideline-concordant treatment (GCT). This study sought to understand underlying barriers to GCT through a root cause analysis approach.

Methods
A single-institution retrospective review of 498 patients with foregut (gastric, pancreatic, and hepatobiliary) adenocarcinoma from 2018 to 2022 was performed. Guideline-concordant treatment was defined based on National Comprehensive Cancer Network guidelines. The Ishikawa cause and effect model was used to establish main contributing factors to non-GCT.

Results
Overall, 34% did not receive GCT. Root causes of non-GCT included Patient, Physician, Institutional Environment and Broader System-related factors. In decreasing order of frequency, the following contributed to non-GCT: receipt of incomplete therapy (N = 28, 16.5%), deconditioning on chemotherapy (N = 26, 15.3%), delays in care because of patient resource constraints followed by loss to follow-up (N = 19, 11.2%), physician factors (N = 19, 11.2%), no documentation of treatment plan after referral to oncologic expertise (N = 19, 11.2%), loss to follow-up before oncology referral (N = 17, 10%), nonreferral to medical oncologic expertise (N = 16, 9.4%), nonreferral to surgical oncology in patients with resectable disease (N = 15, 8.8%), and complications preventing completion of treatment (N = 11, 6.5%). Non-GCT often was a function of multiple intersecting patient, physician, and institutional factors.

Conclusions
A substantial percentage of patients with foregut cancer do not receive GCT. Solutions that may improve receipt of GCT include development of automated systems to improve patient follow-up; institutional prioritization of resources to enhance staffing; financial counseling and assistance programs; and development and integration of structured prehabilitation programs into cancer treatment pathways.
Interdisciplinary Implementation of a Synoptic Reporting Template for Melanoma Nodal Surveillance Ultrasound
Authors: Montgomery Kelsey B. , Duncan Zoey N. , Holder Ashley M. , Burgan Constantine M. , Galgano Samuel J. , Broman Kristy K. 
Published: July 2024

Abstract
Background
With nodal surveillance increasingly used for sentinel lymph node-positive (SLN+) melanoma following the Second Multicenter Selective Lymphadenectomy Trial (MSLT-II), high-quality nodal ultrasonography (U/S) has become a critical need. Previous work has demonstrated low utilization of MSLT-II U/S criteria to define abnormal lymph nodes requiring intervention or biopsy. To address this gap, an evidence-based synoptic template was designed and implemented in this single-center study.

Methods
Sentinel lymph node-positive patients undergoing nodal surveillance at a tertiary cancer center from July 2017 to June 2023 were identified retrospectively. Ultrasound reporting language was analyzed for MSLT-II criteria reported and clinically actionable recommendations (e.g., normal, abnormal with recommendation for biopsy). Following a multidisciplinary design process, the synoptic template was implemented in January 2023. Postimplementation outcomes were evaluated by using U/S reports and provider surveys.

Results
A total of 337 U/S studies were performed on 94 SLN+ patients, with a median of 3 U/S per patient (range 1–12). Among 42 synoptic-eligible U/S performed postimplementation, 32 U/S (76.0%) were reported synoptically. Significant increases were seen in the number of MSLT-II criteria reported (Pre 0.5 ± 0.8 vs. Post 2.5 ± 1.0, p < 0.001), and clinically actionable recommendations for abnormal findings (Pre 64.0% vs. Post 93.0%, p = 0.04). Nearly all surgeon and radiologist survey respondents were “very” or “completely” satisfied with the clinical utility of the synoptic template (90.0%).

Conclusions
Following implementation of a synoptic template, U/S reports were significantly more likely to document MSLT-II criteria and provide an actionable recommendation, increasing usefulness to providers. Efforts to disseminate this synoptic template to other centers are ongoing.
Surveillance Strategies After Primary Treatment for Patients with Invasive Lobular Carcinoma of the Breast: Method of Local Recurrence Detection After Breast-Conserving Surgery
Authors: Clelland Elle N. , Quirarte Astrid , Rothschild Harriet T. , Kaur Mandeep , Mujir Firdows , Record Helena , Wong Jasmine M. , Mukhtar Rita A. 
Published: July 2024

Abstract
Background
Invasive lobular carcinoma (ILC) is the second most common subtype of breast cancer. Although mammography is known to have low sensitivity for ILC, there are no data to guide the optimal surveillance after treatment. We explored surveillance strategies after breast-conserving surgery (BCS) for ILC and determined the proportion of imaging-detected recurrences versus interval cancers.

Methods
From an institutional database of 813 women, we retrospectively identified patients who underwent BCS for stage I–III ILC and subsequently had a recurrence. We categorized patients by surveillance strategy and determined the modality of recurrence detection. Interval cancer rates for local recurrences were compared across surveillance strategies using the Chi-square test. We evaluated overall survival with the log-rank test and a Cox proportional hazards model.

Results
We included 58 patients with ILC who had a recurrence after BCS. Of these, 22 (37.9%) had local recurrence, 27 (46.6%) had distant recurrence, and 9 (15.5%) had both local and distant recurrence. Most patients underwent routine mammographic surveillance (65.2%), with 19.6% having supplemental breast magnetic resonance imaging (MRI) and 15.2% having no surveillance. The interval cancer rate was significantly higher in the mammographic surveillance group compared with the MRI surveillance group (61.9% vs. 16.7%; p < 0.001).

Conclusion
In this study of patients with recurrence after BCS for primary treatment of stage I–III ILC, we found that most local recurrences were not detected by surveillance mammography. These data support further investigation of supplemental imaging beyond mammography specifically for patients with ILC who undergo BCS.
Not all patients with a headache need a CT scan, but they should be listened to, and also with a stethoscope: a report of a large arteriovenous malformation with a loud cranial bruit
Authors: Matthews Thomas , Salzberg Noah , Thayeswaran Trisheekeshan , Jacobs Nikhil , Colwell Niall S. 
Published: July 2024

Background: Arteriovenous malformations (AVMs) are abnormal direct connections between arterial and venous systems, without an interposed capillary bed. This permits high-flow arteriovenous shunting, which precipitates structural changes in the afferent and efferent vessels, namely arterial smooth muscle hyperplasia and thinning of venous walls. Patients with intracranial AVMs typically present with a haemorrhage, headache or seizure. Treatment is either via medical management aimed at control of seizures, headache and blood pressure, or interventional via surgical, radiation or radiologically guided embolisation. Case description: We report the case of a woman in her early 40s presenting with a tonic-clonic seizure against a background of a 31-year history of migraine and an 18-month history of tremors in her right arm. The clinical examination was remarkable for an extremely loud cranial bruit and a right homonymous hemianopia. Imaging diagnosed an 8 cm Martin-Spetzler grade V intracranial arteriovenous malformation in her left parietal lobe, which was deemed unsuitable for operative or radiotherapy-based intervention. Conclusion: The patient was managed through observation and relatively good control of her breakthrough seizures was achieved through the addition of brivaracetam to her lamotrigine and carbamazepine-based therapy, six years after her initial presentation.
Immune cells and checkpoints in pancreatic adenocarcinoma: Association with clinical and pathological characteristics
Authors: Cysneiros Maria Auxiliadora de Paula Carneiro , Cirqueira Magno Belém , Barbosa Lucas de Figueiredo , Chaves de Oliveira Ênio , Morais Lucio Kenny , Wastowski Isabela Jubé , Floriano Vitor Gonçalves 
Published: July 2024

Introduction
Pancreatic adenocarcinoma is an extremely aggressive neoplasm, with many challenges to be overcome in order to achieve a truly effective treatment. It is characterized by a mostly immunosuppressed environment, with dysfunctional immune cells and active immunoinhibitory pathways that favor tumor evasion and progression. Thus, the study and understanding of the tumor microenvironment and the various cells subtypes and their functional capacities are essential to achieve more effective treatments, especially with the use of new immunotherapeutics.

Methods
Seventy cases of pancreatic adenocarcinoma divided into two groups 43 with resectable disease and 27 with unresectable disease were analyzed using immunohistochemical methods regarding the expression of programmed cell death ligand 1 (PD-L1), programmed cell death ligand 2 (PD-L2), and human leukocyte antigen G (HLA-G) molecules as well as the populations of CD4+ and CD8+ T lymphocytes, regulatory T cells (Tregs), and M2 macrophages (MM2). Several statistical tests, including multivariate analyses, were performed to examine how those immune cells and immunoinhibitory molecules impact the evolution and prognosis of pancreatic adenocarcinoma.

Results
CD8+ T lymphocytes and M2 macrophages predominated in the group operated on, and PD-L2 expression predominated in the unresectable group. PD-L2 was associated with T stage, lymph node metastasis, and clinical staging, while in survival analysis, PD-L2 and HLA-G were associated with a shorter survival. In the inoperable cases, Tregs cells, MM2, PD-L1, PD-L2, and HLA-G were positively correlated.

Conclusions
PD-L2 and HLA-G expression correlated with worse survival in the cases studied. Tumor microenvironment was characterized by a tolerant and immunosuppressed pattern, mainly in unresectable lesions, where a broad positive influence was observed between immunoinhibitory cells and immune checkpoint proteins expressed by tumor cells.
Cost-effectiveness and benefits of perinatal health interventions in high-income settings: A protocol for a systematic review of economic evaluations
Authors: Haile Tsegaye G. , Tessema Gizachew A. , Hertzog Lucas , Newnham Elizabeth , Dachew Berihun Assefa , Makate Marshall 
Published: July 2024

Background
Despite ongoing efforts, perinatal morbidity and mortality persist across all settings, imposing a dual burden of clinical and economic strain. Besides, the fragmented nature of economic evidence on perinatal health interventions hinders the formulation of effective health policies. Our review aims to comprehensively and critically assess the economic evidence for such interventions in high-income countries, where the balance of health outcomes and fiscal prudence is paramount.

Methods and analysis
We will conduct a comprehensive search for studies using databases including EconLit (EBSCO), Cost Effectiveness Analysis (CEA) Registry, Medline (Ovid), Embase (Ovid), CINAHL Ultimate (EBSCO), Global Health (Ovid), and PubMed. Furthermore, we will broaden our search to include Google Scholar and conduct snowballing from the final articles included. The search terms will encompass economic evaluation, perinatal health interventions, morbidity and mortality, and high-income countries. We will include full economic evaluations focusing on cost-effectiveness, cost-benefit, cost-utility, and cost-minimisation analyses. We will exclude partial economic evaluations, reports, qualitative studies, conference papers, editorials, and systematic reviews. Date restrictions will limit the review to studies published after 2010 and those in English during the study selection process. We will use the modified Drummond checklist to evaluate the quality of each included study. Our findings will adhere to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) 2020 statement. A summary will include estimated costs, effectiveness, benefits, and the incremental cost-effectiveness ratio (ICER). We also plan to conduct a subgroup analysis. To aid comparability, we will standardise all costs to the United States Dollar, adjusting them to their 2022 value using country-specific consumer price index and purchasing power parity.

Ethics and dissemination
This systematic review will not involve human participants and requires no ethical approval. We will publish the results in a peer-reviewed journal.

Trial registration
We registered our record on PROSPERO (registration #: CRD42023432232).
The Long-Term Efficacy of Conventional Treatments for Bynesian Decay
Authors: Callomon Paul , Tyson Christopher 
Published: July 2024

Abstract
The efficacy of the conventional method for treating Bynesian decay (formerly known as Byne’s disease) is assessed via a review of the outcomes of two remediation projects after 10 and 22 years. The design and implementation of a large-scale triage plan for an incoming collection is described, and the limitations of diagnostic methods for this form of decay are discussed. Examples of arrested and ongoing decay are illustrated.
HANDLING OF OVERDISPERSION CASES IN MORBIDITY DATA IN SELUMA REGENCY
Authors: Sarumpaet Mey Yanti , Nugroho Sigit , Rachmawati Ramya 
Published: July 2024

The problem of overdispersion as a violation of the assumption of equidispersion in Poisson regression is generally caused by sources of unobserved heterogeneity, missing observations on predictor variables, outliers in the data, errors in the specification of the bridging function, and many observed values that are zero. The purpose of this study is to find out the right model and the variables that affect data that occurs overdispersion and excess zero in the case of the number of days of disruption at work, school, or other daily activities due to health complaints. The methods used were Poisson Regression, Negative Binomial Regression, Hurdle Poisson Regression, Zero Inflated Poisson Regression, Zero Inflated Negative Binomial Regression, and Hurdle Negative Binomial Regression. The data used were morbidity taken from data on the number of days of disruption at work, school or other daily activities due to health complaints in Seluma district, Bengkulu Province. It was found that the best model is Zero Inflated Negative Poisson with the smallest Akaike Information Criterion (AIC) value of 1620.609 and the variables that have a significant effect on the log model and the logit model are marital status and work variables.
Visual Analysis of Dynamic Assessment Research Based on CiteSpace (1990–2022)
Authors: Nian Yuxiu , Qin Lili 
Published: July 2024

Abstract
This study uses CiteSpace to map the scientometric analysis of dynamic assessment (DA) research in the Web of Science core collection from 1990 to 2022 in the areas of psychology, education and language learning. Firstly, the study found that DA was initially employed in the fields of psychology and special education, and has been gaining attention from second language acquisition researchers in recent years. And Vygotsky, the representative figure of sociolcultural theory, has the highest influence, and Budoff has the greatest degree as a bridge. Secondly, five research topics are found through keyword clustering, which are early identification, group dynamic assessment, short-term progress monitoring, computerized dynamic assessment and teacher education. At the same time, the analysis of burst reference shows that the computerized dynamic assessment will be the trend in the future, and dynamic assessment of second language tends to use mixed research method. Through a review of previous studies, this paper explores the paradigms and methods of empirical research in DA, hoping to provide new alternatives for future research.