bluuebunny/crossref_metadata_2025_split huggingface dataset:
Kinetics of Blast Clearance in Cerebrospinal Fluid (CSF) Detected on Flow Cytometric Immunophenotyping (FCM), but Negative By Cytopathology in Newly Diagnosed Acute Lymphoblastic Leukemia Patients
Authors: Seth Tulika , Keerthana Kavya , Dass Jasmita , Agarwal Mukul , Pushpam Deepam , Mallick Saumyaranjan 
Published: December 2024

Background: Flow cytometric immunophenotyping (FCM) detects two-fold higher CSF disease. Limited data on kinetics of CNS disease detected in this manner. Our study aimed to identify and follow course of CSF FCM+ in newly diagnosed ALL. Serial CSF FCM examinations performed to detect and see persistence of blasts. Identify risk factors for CSF involvement any correlation with post-induction measurable residual disease (PI-MRD).
Methods: Enrolled 125 patients newly diagnosed treatment naïve ALL patients from April 2022 to December 2023, Ethics approval and informed consent. CNS status assessed CSF cytopathology and FCM. Patients categorized as CNS1, CNS2, and CNS3 based on St Jude's criteria. CNS1 patients further divided into Cyto-FCM+ and Cyto-FCM - groups. Additional CSF FCM samples collected D+15 and D+28. All FCM analysis performed on BD FACS Canto II flow cytometer and BD FACS Diva v8.0.3 used for analysis. Patients received augmented BFM or adult protocol. Intrathecal Mtx given after baseline CSF and administered on D+15 and D+28 of induction.
Statistical analysis- Qualitative variables assessed using Chi-square test or Fisher's exact test. Quantitative variables assessed using ANOVA with post-hoc Bonferroni or Kruskal-Wallis test, p-value&lt;0.05 was considered statistically significant.
Results: total 125 patients, 104 B-ALL, 16 T-ALL, and 5 MPAL, male-to-female ratio 3:1. Median age 16 years (1-57). CNS signs or symptoms present in 17 patients (13.6%) they had CNS2 or CNS3 status. Of remaining 108 patients, 22 (20.4%) were Cyto-FCM+, and 86 (79.6%) were Cyto-FCM-
Three patients in Cyto-FCM+ group died before D+15. Of remaining 19 patients repeat CSF, FCM detected persistent blasts in 2 (10.5%) while 17 (89.5%) showed blast clearance. The 2 patients with persistent CNS blasts cleared blasts D+15 and D+28.
Cyto-FCM- group vs CNS2/3 group significantly lower number of NCI high-risk patients (69.8% vs 100%). Cyto-FCM+ group significant hepatomegaly compared to Cyto-FCM- group (72.7% vs 46.5%). CNS2/3 and Cyto-FCM+ group higher median total leucocyte counts (TLC ) compared to Cyto-FCM-- and Higher LDH (589 vs 651 vs 349.5 IU/L, p-0.012 and 0.02). Receiver operator characteristic curve analysis showed TLC &gt;6.3X10^9/L and LDH more than 314IU/L could predict Cyto-FCM+ with a sensitivity of 84.6% and 87.2% (p=0.0005 and 0.0006) respectively. Lowest end-of-induction MRD positivity was seen in Cyto-FCM- group.
Conclusions: FCM detects CSF higher involvement in newly diagnosed ALL patients. However, ~90% patients cleared CSF by standard intrathecal methotrexate by D+15 and all patients cleared disease by D+28 without extra intrathecal therapy. Longterm effect impacts needs evaluation.
Dietary Sucrose Exacerbates Antibiotic-Induced Microbiome Injury in Allo-HCT
Authors: Rangesa Madhumitha , Dai Anqi , Adintori Peter , Jogia William , Fei Teng , Waters Nicholas , Baichoo Mirae , Ballweg Annamaria , Sahu Sukanya , Schluter Jonas , van den Brink Marcel R.M. , Peled Jonathan U. , Perales Miguel-Angel 
Published: December 2024

Patients with blood cancers who undergo allogeneic hematopoietic cell transplantation (allo-HCT) are typically hospitalized for several weeks while they receive chemotherapy, sometimes irradiation, and antibiotics. Nutrition influences the composition of the gut microbiome, yet its contribution to microbiome disruption during cancer treatment remains poorly understood. We profiled fecal microbiome composition and detailed dietary intake in 158 allo-HCT patients. Intake of sugar-enriched foods during antibiotic exposure predicted low fecal microbiome α-diversity and expansion of Enterococcus, two patterns of microbiome we previously identified as predictors of mortality in this population.
To validate this finding, we developed a simple mouse model of antibiotic-induced expansion of Enterococci endogenous to the mouse gut microbiome by administering a single subcutaneous dose of the carbapenem antibiotic biapenem to C57BL/6 mice induced a moderate bloom of Enterococci, as assessed by dilution plating on selective agar. In line with our observations in human patients, supplementation of the disaccharide sucrose to the diet intensified the Enterococcus expansion, leading to a 51.8-fold median increase at day 3 (p = 0.002) and a 42.4-fold median increase at day 6 (p = 0.030). Importantly, sucrose alone, without antibiotics, did not influence the abundance of Enterococcus.
The monosaccharide components of sucrose, fructose and glucose, were each sufficient to exacerbate the antibiotic-induced Enterococcus bloom (fructose median fold change on day 3: 104.7, p = 0.002; glucose median fold change on day 3: 105.1, p = 0.003), although the effect was not as sustained as that of sucrose, as by day 6, no significant differences were observed in colony counts between fructose- and glucose-treated samples and diet vehicle-treated samples. A similar pattern was observed in mice that were irradiated and allografted with T-cell-depleted grafts to model the early post-transplant period: a bloom of Enterococcus induced rapidly by the carbapenem that resolved 5 days later, and sucrose prolonged the relative expansion. These findings underscore the influence of diet on gut microbiota diversity and composition in HCT patients receiving antibiotics, highlighting the need for targeted nutritional interventions to mitigate adverse microbiome-related outcomes in this vulnerable population. Avoiding sugar-enriched foods while taking antibiotics may also have relevance outside the setting of cancer treatment. The general recommendation to limit consumption of sweets for cardiovascular health might, with further study, be tailored to abbreviated periods of avoidance to mitigate microbiome disruption during antimicrobial therapy.
Role and Mechanisms Exploration of Histamine and Its Receptors in the Progression of Peripheral T-Cell Lymphoma
Authors: Jin Hui , Wang Ling , Ren Yimin , Wu Zijuan , Shi Wenyu , Li Jianyong 
Published: December 2024

Introduction: Peripheral T-cell lymphoma (PTCL) is a group of malignant lymphomas originating from mature T cells, characterized by clinical aggressiveness, rapid progression, and dismal survival outcomes. Elevated levels of inflammatory reactants are closely associated with poor prognosis. The incidence of PTCL in China is much higher than that in European and American countries, while basic and clinical research is relatively lagging behind. Hence, there is an urgent need for a comprehensive and systematic analysis of the tumor microenvironment of PTCL and discover new effective targets as well as reliable prognostic indicators.
Objectives: This study intends to progressively analyze the spatial characteristics of PTCL tumors and the inflammatory microenvironment at the genomic, cellular, and animal levels, using single-cell RNA sequencing combined with image mass cytometry and other multi-omics methods. On this basis, it focuses on the role and molecular mechanism of the Histamine-HRH2 axis in PTCL disease progression and drug resistance, verifying it at the cellular and animal levels. The project aims to fully explore potential therapeutic targets, providing new ideas for optimizing treatment schemes and overcoming drug resistance in PTCL patients.
Methods: By conducting single-cell RNA sequencing (scRNA-seq) and imaging mass cytometry (IMC), we conducted a comprehensive investigation of the complexity of inflammatory microenvironmen in PTCL. We unveiled the role and molecular mechanism of the Histamine-HRH2 axis in the progression of PTCL as well as the potential drug resistance regulatory mechanisms. Immunohistochemistry, immunofluorescence, and publicly available microarray datasets were used to validate these findings.
Results: The present study highlighted histamine, an inflammatory mediator, was abundant in the microenvironment of PTCL and was associated with poor prognosis of patients. Histamine, upon interaction with the HRH2 receptor on tumor cell surfaces, triggers the secretion of CSF1, consequently inducing M2 macrophage polarization and mediates immune suppression. The expression of p-CREB and CEBPB were upregulated after the treatment of histamine, which mediated the transcriptional activation of CSF1. In addition, we uncovered that histamine and CSF1 played important roles in remodeling the tumor microenvironment of PTCL, and combination therapy with antihistamines and CSF1R inhibitors may effectively enhance tumor cell killing effect of HDAC inhibitor.
Conclusions: In this study, we constructed comprehensive single-cell atlas of PTCL tumors and inflammatory microenvironment, using single-cell RNA sequencing combined with image mass spectrometry. On this basis, for the first time, we elucidated the role and molecular mechanism of histamine/HRH2 receptor axis in the progression of PTCL, explored potential therapeutic targets to provide new strategies for optimizing clinical treatment of PTCL patients.
Genetic disruption of Blimp-1 drastically augments the antitumor efficacy of BCMA-targeting CAR T cells
Authors: Battram Anthony M. , Mañé-Pujol Joan , Moreno David F. , Oliver-Caldés Aina , Carpio Judit , Cardus Oriol , Rodríguez-Lobato Luis Gerardo , Urbano-Ispizua Álvaro , Fernández de Larrea Carlos 
Published: December 2024

Abstract
Chimeric antigen receptor (CAR) T cells directed against B-cell maturation antigen (BCMA) are an effective treatment for multiple myeloma (MM), but short persistence and frequent relapses are challenges for this immunotherapy. This lack of durability has been attributed to the premature terminal differentiation of CAR T cells, which prevents the formation of long-lived memory cells that maintain antitumor responses. To improve long-term efficacy, we used CRISPR/CRISPR-associated protein 9-mediated gene editing to ablate the expression of the transcription factor Blimp-1. Blimp-1 knockout (KO) CAR T cells displayed a memory-like phenotype compared with control (Mock) CAR T cells, but had reduced effector function, with a striking loss of granzyme B. However, in a murine model of advanced MM, Blimp-1 KO CAR T cells effectively slowed or even prevented disease progression, significantly outperforming Mock CAR T cells in improving survival (P = .006). To understand this enhanced in vivo effectiveness, Blimp-1 KO CAR T cells were characterized after being repeatedly challenged with tumor cells in vitro. In this setting, Blimp-1 KO CAR T cells maintained a highly active state with high expression of memory markers, but, crucially, demonstrated enhanced effector function and increased energetic capacity. RNA-sequencing analysis of tumor-exposed Blimp-1 KO CAR T cells confirmed the presence of a memory-like transcriptomic signature and, additionally, revealed enhanced ribosome biogenesis and repressed CAR T-cell dysfunction as mechanisms that could contribute to improved antitumor activity. Put together, our findings show that dampening Blimp-1 expression altered the phenotype and function of anti-BCMA CAR T cells, leading to augmented therapeutic efficacy in MM.
Agent-based modelling of Mycobacterium tuberculosis transmission: a systematic review
Authors: Bui Viet Long , Hughes Angus E. , Ragonnet Romain , Meehan Michael T. , Henderson Alec , McBryde Emma S. , Trauer James M. 
Published: December 2024

Abstract
Background
Traditional epidemiological models tend to oversimplify the transmission dynamics of Mycobacterium tuberculosis (M.tb) to replicate observed tuberculosis (TB) epidemic patterns. This has led to growing interest in advanced methodologies like agent-based modelling (ABM), which can more accurately represent the complex heterogeneity of TB transmission.

Objectives
To better understand the use of agent-based models (ABMs) in this context, we conducted a systematic review with two main objectives: (1) to examine how ABMs have been employed to model the intricate heterogeneity of M.tb transmission, and (2) to identify the challenges and opportunities associated with implementing ABMs for M.tb.

Search methods
We conducted a systematic search following PRISMA guidelines across four databases (MEDLINE, EMBASE, Global Health, and Scopus), limiting our review to peer-reviewed articles published in English up to December 2022. Data were extracted by two investigators using a standardized extraction tool. Prospero registration: CRD42022380580.

Selection criteria
Our review included peer-reviewed articles in English that implement agent-based, individual-based, or microsimulation models of M.tb transmission. Models focusing solely on in-vitro or within-host dynamics were excluded. Data extraction targeted the methodological, epidemiological, and computational characteristics of ABMs used for TB transmission. A risk of bias assessment was not conducted as the review synthesized modelling studies without pooling epidemiological data.

Results
Our search initially identified 5,077 studies, from which we ultimately included 26 in our final review after exclusions. These studies varied in population settings, time horizons, and model complexity. While many incorporated population heterogeneity and household structures, some lacked essential features like spatial structures or economic evaluations. Only eight studies provided publicly accessible code, highlighting the need for improved transparency.

Authors’ conclusions
ABMs are a versatile approach for representing complex disease dynamics, particularly in cases like TB, where they address heterogeneous mixing and household transmission often overlooked by traditional models. However, their advanced capabilities come with challenges, including those arising from their stochastic nature, such as parameter tuning and high computational expense. To improve transparency and reproducibility, open-source code sharing, and standardised reporting are recommended to enhance ABM reliability in studying epidemiologically complex diseases like TB.
Knowledge, attitudes, and self-perceived skills regarding ultrahigh risk (UHR) for psychosis and schizophrenia in primary care physicians: new insights from Tunisia
Authors: Fekih-Romdhane Feten , Jaoua Amira , Homri Wided , Hakiri Abir , Cheour Majda , Loch Alexandre Andrade , Hallit Souheil 
Published: December 2024

Abstract
Background
There is evidence indicating that an important proportion of young people at ultrahigh risk (UHR) for psychosis do consult in primary care, but their identification may be hindered by multiple factors, such as primary care physicians (PCPs)’ limited skills and perceived stigma toward the condition. This study aimed to investigate attitudes/beliefs toward both UHR and schizophrenia and perceived self-efficacy in screening for, diagnosing, and managing these conditions among PCPs. The secondary objective was to determine the potential effects of psychosis level (UHR vs. schizophrenia) on PCP’s views.

Methods
A cross-sectional survey was carried out among Tunisian PCPs working in primary care setting in Tunisia (N = 232, 66.4% females, mean age of 47.5 ± 9.9 years). An anonymous paper-and-pencil self-administered questionnaire was adopted to collect data. PCPs were asked to read vignettes describing individuals with UHR and schizophrenia and answer a series of questions that followed.

Results
The schizophrenia vignette aroused significantly more feelings of “need to help the person” than the UHR vignette (87.8% vs. 88%, p = .022). The perceptions that the person depicted in the vignette is “strange” and “not intelligent” were more frequently endorsed for UHR than schizophrenia (18.7% vs. 16%, p = 0.028, and 8.4% vs. 5.6%, p = 0.043, respectively), whereas the person with schizophrenia was perceived are more dangerous than the UHR person (38.4% vs. 25.2%, p = 0.033). Only 28.9% and 14% of participants agreed that they have the necessary skills to make the diagnosis and manage the condition depicted in the UHR vignette, respectively.

Conclusion
Findings indicated that a high proportion of our Tunisian PCPs show a deficit in identifying both UHR and schizophrenia diagnoses. Given that PCPs can be key sources of referral of at-risk young help-seekers to specialized early intervention services, urgent interventions are needed to help PCPs enhance their knowledge and reduce stigma associated with psychosis.
Comparison of Survivorship Care Guidelines for Patients With Lymphoma: Recommendations for Harmonization and Future Research Agenda
Authors: Valcarcel Bryan , Savage Kerry J. , Link Brian K. , Leonard John P. , Kelly Kara M. , Thanarajasingam Gita , Cerhan James R. , Pro Barbara , Gordon Leo I. , Thompson Carrie A. , Smith Sonali M. , Morton Lindsay M. 
Published: December 2024

PURPOSE
Lymphomas are a heterogeneous group of diseases that develop in individuals of all ages and have variable prognoses. Improved survival resulting from therapy advances has led to the emergence of diverse late effects. Although several (US)–based organizations have developed survivorship guidelines, the distinct features of lymphoma subtypes and diverse therapies used raise concerns regarding their applicability to lymphoma survivors. We compared survivorship recommendations (outside primary disease monitoring) between US clinical guidelines.

METHODS

We extracted information from 17 guidelines from five US-based organizations: ASCO (n = 11), American Cancer Society (n = 1), Children's Oncology Group (n = 1), Center for International Blood and Marrow Transplant Research (n = 1), and the National Comprehensive Cancer Network (n = 3). Guidelines were evaluated to determine whether they offer recommendations on
physical effects
,
psychosocial and quality of life
(
QOL
), and
health promotion and prevention
. Comparisons were focused on second primary malignancy, cardiovascular complications, and vaccination.

RESULTS

Survivorship recommendations on
physical effects
and
psychosocial and QOL
mainly differ in the timing and approaches for screening. Vaccination recommendations were primarily derived from other cancer populations. Identified research gaps were a lack of understanding of the risk of late effects across lymphoma subtypes, the role of social determinants of health in survivorship, and the lack of a survivorship care model that integrates lymphoma subtypes and treatment exposures.

CONCLUSION
This study raises awareness about the complexity and challenges of managing survivors under the umbrella diagnosis of lymphoma. The inconsistency and incompleteness of existing guidelines may lead to suboptimal survivorship care. We propose expert-based research priorities to address gaps and unmet needs to help develop risk-based follow-up recommendations to optimize survivorship care for lymphoma survivors.
Cancer-Control Outcomes of Patients With Metastatic Castration-Resistant Prostate Cancer With
BRCA
Gene or Tumor Suppressor Mutations Undergoing 177-Lutetium Prostate-Specific Membrane Antigen Radioligand Therapy
Authors: Wenzel Mike , Koll Florestan , Hoeh Benedikt , Humke Clara , Reis Henning , Wild Peter , Steuber Thomas , Graefen Markus , Tilki Derya , Sabet Amir , Gröner Daniel , Chun Felix K.H. , Mandel Philipp 
Published: December 2024

PURPOSE
Several tumor gene mutations are known for metastatic castration-resistant prostate cancer (mCRPC). The individual response to 177-lutetium prostate specific membrane antigen radioligand therapy (Lu-PSMA) is under current investigation regarding the genomic profile of patients with mCRPC.

MATERIALS AND METHODS

We relied on the FRAMCAP database and compared progression-free survival (PFS) and overall survival (OS) rates of patients with mCRPC with breast cancer–related antigen (
BRCA
) or tumor suppressor gene mutations (
TP53
,
PTEN
,
RB1
). Specifically, subgroup analyses were performed for patients with Lu-PSMA–treated mCRPC.

RESULTS

Of 194 patients with mCRPC, 22% was
BRCA1/2
versus 14%
PTEN/TP53/RB1
versus 63% without one of these mutations. Patients with no mutation harbored a significantly lower Gleason score of 8-10, relative to
BRCA
and
PTEN/TP53/RB1
patients. In PFS analyses of first-line mCRPC, no difference between all three groups was observed, whereas the median OS differed significantly with 46.3 versus 48.7 versus 95.4 months for
BRCA
versus
PTEN/TP53/RB1
versus no mutated patients (
P
< .05). In univariable Cox regression models, BRCA-mutated patients were at higher risk of death (hazard ratio, 2.57;
P
< .01), whereas
PTEN/TP53/RB1
patients were not (
P
= .4). Of 87 patients with Lu-PSMA–treated mCRPC, significant differences in PFS and OS were observed (both
P
≤ .02). In univariable and multivariable Cox regression models, BRCA-mutated Lu-PSMA patients were at higher risk of death, whereas
PTEN/TP53/RB1
patients had similar outcomes as no mutated patients.

CONCLUSION

In real-world setting, substantially lower OS in mCRPC is observed for
BRCA
- and
PTEN/TP53/RB1
-mutated patients, whereas no difference in first-line PFS could be computed. In Lu-PSMA–treated patients, worst outcomes were observed for
BRCA
patients.
Influence of Epithelial-Mesenchymal Transition on Risk of Relapse and Outcome to Eribulin or Cyclin-Dependent Kinase Inhibitors in Metastatic Breast Cancer
Authors: Chan Arlene , Gill Jespal , Chih HuiJun , Wright Sarah Christine Elisabeth , Vasilevski Natali , Eichhorn Pieter Johan Adam 
Published: December 2024

PURPOSE
The presence of epithelial-mesenchymal transition (EMT) in breast cancer (BC) cells has been linked to worse prognosis and may influence response to systemic treatment. We explored the effect of EMT in tumor samples of patients with metastatic BC on disease-free interval and overall survival in those patients receiving eribulin or cyclin-dependent kinase 4/6 inhibitors (CDK4/6i).

MATERIALS AND METHODS

Key inclusion criteria included available archived primary BC tissue and, where available, matched metastatic biopsy. Patients received eribulin and/or a CDK4/6i in the metastatic setting. Specimens were assessed for biomarkers by immunohistochemistry (CDH1, AE1/3, VIM, CDH2, ZEB1, pSMAD2, and SMAD4) and gene expression by droplet digital polymerase chain reaction (
CDH1
,
CDH2
,
SNAI1
&
2
,
TWIST1
,
VIM
,
PTEN
, and
ZEB1
&
2
).

RESULTS

Between 2002 and 2020, 127 patients were included (95 early-stage disease at diagnosis with metastatic relapse, 32 de novo metastatic disease). In metastatic samples, presence of ZEB1 overexpression was associated with shorter time to recurrence (48.1 months shorter;
P
= .003), with pSMAD2 overexpression suggesting clinical significance of 52.0 months shorter;
P
= .01. High gene expression levels for SNAIL1,
TWIST1
, and
PTEN
in the primary BC were associated with significantly longer survival in patients who received eribulin (
P
< .05); high
VIM
was associated with a clinically relevant trend toward shorter survival after a CDK4/6i (
P
= .013).

CONCLUSION
We demonstrate in our exploratory study that biomarkers involved in the process of EMT could have a prognostic impact in a cohort of patients with BC uniformly treated and with long-term follow-up. Genes known to be involved in EMT were associated with improved eribulin efficacy, while suggesting a poorer outcome with CDK4/6i.