bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of Dietary Profiles and Nutritional Status Among Patients with Hematologic Diseases: A Prospective Cohort Study
Authors: Yu Xiao , Zhao Jingyu , Xu Jing , Li Liyun , Dong Jin , Yuan Weiping , Shi Jun , Kuang Zhexiang 
Published: December 2024

Objectives Hematologic patients need to maintain a reasonable diet during treatment to enhance their nutritional status, as it is crucial in supporting their overall health and facilitating recovery. This study aims to explore the latent profiles of dietary intake among patients with hematologic diseases and identify the association of dietary profiles with nutrition status.
Methods A prospective cohort study involving 159 hematologic patients would receive the immunosuppressive therapy or chemotherapy was conducted. Nutritional risk screening (NRS-2002) and Malnutrition Universal Screening Tool (MUST) were used for nutritional screening at admission and post-treatment. The dietary intake was consistently recorded by clinical research nurses in real-time daily throughout treatment. Latent profile analysis was performed to identify mutually exclusive profiles based on the daily intake of six food categories, including cereals and tubers, vegetables, fruits, dairy products, poultry and meat, and eggs. Multinomial logistic regression was employed to measure the association of dietary profiles and nutritional status by adjusting sociodemographic and treatment-related variables.
Results A statistically significant difference was observed in the risk changes of nutritional status as screened by both NRS-2002 and MUST between individuals before and after treatment (P were all &lt;0.001). Three dietary profiles were identified with varying consumption of different types of foods, characterized by low, moderate, and high intake of most foods. Assessed by MUST, patients in the low intake group had a higher risk of malnutrition post-treatment than those in the moderate intake group (OR=3.14, 95%CI: 1.11-8.90). However, there was no difference in malnutrition risk changes across treatment between moderate intake and high intake groups (OR=1.57, 95%CI: 0.66-3.74). The results of multinomial logistic regression showed no significant difference in risk changes across treatments as assessed by NRS-2002 among the three dietary profiles.
Conclusions Hematologic patients with lower food intake in both quantity and variety during treatment may have an increased risk of malnutrition. Improving dietary practices for hematologic patients is essential to achieve better health outcomes.
Identifying the Key Genes of Epstein Barr Virus Regulated Tumour Immune Microenvironment of Diffuse Large B Cell Lymphoma
Authors: Luo Qingqing , Yu Li , Luo Yi 
Published: December 2024

Objective: Epstein Barr virus (EBV) plays a crucial role in the pathogenesis of diffuse large B cell lymphoma (DLBCL) by infecting normal cells and influencing the composition of the tumor immue microenvironment (TIME). However, a systematic bioinformatics analysis of key genes regulating immune infiltration in EBV+ DLBCL is currently lacking.
Methods: We utilized the GEO database to identify differential genes (DEGs) and analyze immune infiltration profiles in EBV+ DLBCL (N=23) and EBV- DLBCL (N=28). Weighted gene co-expression analysis (WGCNA) was employed to identify gene modules associated with EBV-induced immune infiltration. Immune-related genes were sourced from the ImmPort database. Immune-related hub genes in EBV+ DLBCL were identified through an integrated analysis of DEGs, WGCNA, ImmPort data, and protein-protein interaction (PPI) networks. Additionally, single-cell RNA sequencing (scRNA-seq) was performed on tumor tissue from one EBV+ DLBCL case to validate hub gene expression in immune cells.
Results: We identified 1215 genes with differential expression between EBV+ and EBV- DLBCL, and enrichment analysis showed that DEGs were mainly enriched in immune-related pathways. EBV+ DLBCL exhibited distinct profiles of tumor-infiltrating immune cells compared to EBV- DLBCL, with more plasma cells, CD8+ T cells, T cell CD4 memory-activated, NK cell-activated, monocytes, macrophage M1, dendritic cell-activated, thymocyte-activated, oocytes, neutrophils and less B-cell naive, T-cell CD4 naive, T-cell CD4 memory resting, T-cell follicular helper, T-cell regulatory, macrophage M0, and dendritic cell resting. Ultimately, we identified three immune-related hub genes-CD28, IL18, and CD247-that were down-regulated and correlated with poor prognosis in EBV+ DLBCL. scRNA-seq confirmed that these hub genes were predominantly expressed in T cell, NK cell and monocytes clusters.
Conclusions: EBV infection significantly alters the TIME of DLBCL, potentially through the down-regulation of CD28, IL18, and CD247, which may contribute to the observed poor prognosis in EBV+ DLBCL patients. These identified hub genes provide new insights into potential prognostic markers and therapeutic targets for EBV+ DLBCL.
Nationwide Analysis on Incidences and Treatment Outcomes of T-Cell Subtype Lymphomas Based on Health Insurance Review & Assessment Service
Authors: Lee Jungmin , Jang Youngeun , Lee Yunji , Cho Hee Jeong , Moon Joon Ho , Do Young Rok , Sohn Sang Kyun , Baek Dong Won 
Published: December 2024

Background
The incidence of T-cell lymphomas varies by region worldwide, with a higher occurrence in Far East Asian countries compared to Western countries. There is a lack of recent statistical data on the incidence and clinical outcomes of T-cell lymphomas. The current standard treatment is an anthracycline-containing chemotherapy, but the treatment outcomes indicate that further improvement is needed. Therefore, upfront stem cell transplantation (SCT) is performed for patients who are suitable candidates. The aim of this study is to analyze the incidence and clinical outcomes of T-cell lymphomas in Korea.
Methods
Using data from the Health Insurance Review and Assessment Service of South Korea, we retrospectively analyzed newly diagnosed T-cell lymphomas patients from January 2005 to December 2021. We studied 12,616 patients, 43 patients were excluded from the study due to data error.
Results
A total of 12,573 patients were registered between January 2005 and December 2021. The disease incidence was higher among Koreans in age groups 60-69 (n = 2598, 20.7%) (Figure 1A). Male had a higher incidence (n = 7615, 61%) than female (n = 4958, 39%). Peripheral T-Cell Lymphoma-not otherwise specified (PTCL-NOS) was the most common subtype (n = 3200, 25.5%), followed by Extranodal natural killer (NK)/T- cell lymphoma, nasal type (n = 1671, 13.3%), other mature T/NK-cell lymphoma (n = 1659, 13.2%), mycosis fungoides (n = 1644, 13.1%), angioimmunoblastic T-cell lymphoma (AITL, n = 1483, 11.8%), ALK-positive anaplastic large cell lymphoma (ALCL, n = 396, 3.1%), and ALK-negative ALCL (n = 328, 2.6%) (Figure 1B). CHOP (n = 2859, 56.4%) and CHOEP (n = 577, 11.4%) were used as first-line regimens in PTCL, ALCL and AITL. NK/T cell lymphoma was treated as a first-line therapy with cisplatin plus concurrent radiotherapy (n=389, 7.7%), VIPD(n= 145, 2.8%), VIDL(n= 5, 0.1%) and SMILE (n= 635, 12.5%). Stem cell transplantation was given as a part of front-line therapy (n = 890, 17.5%). Autologous SCT was given to 149 patients (2.9%) and allogeneic SCT was 741 patients (14.6%). The 5-year overall survival (OS) of T-cell lymphomas were 57.8% in patients who received SCT and 42.1% in patients who did not receive SCT (Figure2A). The 5-year OS of PTCL-NOS were 54.2% in patients who received SCT and 30.7% in patients who did not receive SCT. (Figure 2C). Upfront use of combined treatment with chemotherapy and SCT showed better OS than chemotherapy alone in T-cell lymphomas. Patients who received allogeneic SCT had a more favorable progression-free survival.
Conclusions
The incidence was highest in the age group 60-69 years. PTCL-NOS was the most common subtype of T cell lymphomas. Upfront SCT was significantly related to survival benefit.
Indolent Lymphoma: Well Tolerated, Fixed Duration Treatment Involving Bendamustine, Rituximab and Acalabrutinib for Front-Line Waldenström's Macroglobulinaemia That Induce Deep Clinical Responses
Authors: Suleman Adam , Roos Kim , Mangoff Kathryn , Jiang Yidi , Klein Gail , McClure Rebecca , Forward Nicholas Allen , Shafey Mona , Nikonova Anna , Sebag Michael , MacDonald David , Villa Diego , Sandhu Irwindeep , Aljama Mohammed , Larouche Jean-Francois , Simmons Heidi , Gallucci Monica , Tomlinson George A. , Berinstein Neil 
Published: December 2024

Background: Waldenström's macroglobulinaemia (WM) is an uncommon lymphoproliferative disorder. An optimal first-line therapy for WM has not been defined. We postulated that combining bendamustine and rituximab (BR) with the second generation covalent BTK inhibitor Acalabrutinib would result in deeper responses as measured by complete response (CR) and very good partial response (VGPR) rates, and provide a longer duration of response.
Objectives: The primary objective of this trial is to document the CR and VGPR rates.
Methods: The BRAWM clinical trial (NCT04624906) combines BR with acalabrutinib in a one-year, fixed duration treatment course of six 28-day cycles BR and 365 days of concurrent acalabrutinib. This ongoing trial is taking place at 9 clinical sites across Canada. The Intent to Treat (ITT) population includes all participants who have started treatment and were evaluable for safety. Participants who reached cycle 7 were evaluable for response. The sample size was calculated to be able to detect a CR + VGPR rate whose lower level of confidence is greater that the historically defined CR + VGPR rates of 23%. Clinical responses were defined using 6th IWWM. Minimal residual disease (MRD) negativity, assessed with clonoSEQ assay, was a secondary endpoint.
Mutational analysis of screening biopsy samples from participants with adequate sample for assessment (n=56), showed 50 with MYD88 L265P mutation, 16 with a CXCR4 mutation of which 8 were S338fs, and 1 with a TP53 l195T mutation. Preliminary minimal residual disease (MRD) analysis of peripheral blood (PB) and bone marrow (BM), using next generation sequencing with a sensitivity of 10-6, shows that most evaluable participants (those with MRD samples at two or more time-points) have become MRD negative in PB, with increasing rates of BM MRD negativity over time. From baseline screening levels, there was a median log reduction in the PB of 4.42 (IQR 1.32) by cycle 7, 4.11 (IQR 1.25) by cycle 12, and 4.06 (IQR 0.81) by month 18. Uni- and multi-variate analyses of clinical variables that may be associated with clinical and MRD outcomes are underway.
Conclusions: Bendamustine, rituximab and acalabrutinib front-line therapy for WM is safe and well tolerated in a relatively elderly population with a toxicity profile consistent with the utilized drugs and not greater than that seen with BR and Placebo in the randomized ECHO trial in untreated Mantle Cell Lymphoma. Initial clinical results show that this treatment is associated with a very high proportion of CR + VGPRs as well as MRD negativity.
Machine Learning Analysis Was Conducted to Construct a Novel Model for Modulating the Clinical Manifestations and Predicting the Response to Glucocorticoids in Immune Thrombocytopenia
Authors: Zhang Jing , Chen Jia , Yang Renchi , Zhang Lei 
Published: December 2024

Abstract:
Aim: In this study, a novel prediction model was established using Recursive Feature Elimination (RFE) to predict the clinical manifestations of Immune Thrombocytopenia (ITP) and the response to glucocorticoids.
Methods: This study consisted of two parts: the establishment and validation of the prediction model. A total of 1019 ITP patients were included, and general information such as age, gender, medical history, and laboratory test results were recorded. RFE, SVM, and Logistic regression models were compared by ROC analysis, and the raw data were preprocessed for feature extraction. The RFE was then used to construct the prediction model, and patients were classified into high-risk group (n=464) and low-risk group (n=555) based on their risk levels. The model performance was evaluated using cross-validation, and the results were subsequently predicted.
Results: The results of this study showed that the RFE prediction model established had good predictive efficacy for the clinical manifestations of ITP patients. A total of 39 variables were extracted, and univariate analysis revealed that age, B lymphocyte surface antigen (CD19B), mean corpuscular volume (MCV), and hemoglobin (Hb) were the main influencing variables (P&lt;0.05). After comparing the models, the ROC of RFE was 0.902 (0.884-0.920), SVM was 0.511 (0.501-0.522), and Logistic regression was 0.680 (0.646-0.715). Since RFE had the highest ROC, it was selected as the prediction model for this study. In the training cohort, the RFE model had a specificity of 0.789 and a sensitivity of 0.858. The threshold for high and low-risk classification was set at 0.33. In the prediction of clinical and laboratory differences, the threshold of the RFE model cutoff value was 16.5, with a specificity of 0.43 and a sensitivity of 0.70. In the validation cohort, the RFE model had a ROC of 0.962, which was higher than the other two models.
Conclusion: In this study, we successfully constructed a new model using machine learning techniques that can analyze and predict the clinical manifestations of patients with immune thrombocytopenia (ITP), as well as predict their response to glucocorticoid treatment. This model holds promise in providing more accurate treatment recommendations to clinical physicians and aiding in the development of individualized treatment strategies, thereby improving the treatment outcomes and quality of life for ITP patients. Further research can be conducted to expand the sample size and integrate other clinical data to further optimize and validate the performance of this model.
Keywords: Machine learning; Predictive model; Immune thrombocytopenia; Clinical manifestations; Glucocorticoids therapy
Thrombosis at High Altitude Is Not Associated with Increased Transferrin
Authors: Amaru Ricardo , Prchal Josef T. , Paton Daniela , Carrasco Mireya , Mancilla Emma , Gordeuk Victor R. 
Published: December 2024

Bolivian Andean Aymara highlanders have been living at 4000 meters for 14,000 years, and have developed evolutionary genetic adaptations to hypoxia (PMID:28448578; PMID:29100088; PMID:36980912). These include EGLN1 encoding prolyl hydroxylase 2 (PHD2), a regulator of transferrin transcription. Transferrin increases in hypoxia and iron deficiency (PMID: 9242677); contrasting reports indicate that elevated transferrin associates with thrombosis in mice but decreased thrombosis in a congenital disorder of hypoxia-sensing (PMID: 36040436; PMID: 31310728; PMID: 8281634).
We analyzed clinical and laboratory data of Andean Aymara patients with High-Altitude Anemia (n=137, mean age 45 years, female gender 79%,) or High-Altitude Erythrocytosis (n=149, mean age 56 years, female gender 30%) with transferrin results in their medical records.
Iron deficiency was present in 57% of anemia and 23% of erythrocytosis patients. Mean (SD) transferrin concentration was 3.08 (1.25) g/L in anemia and 3.34 (0.84) g/L in erythrocytosis patients. Thrombosis history was present in 8% of anemia and 13% of erythrocytosis patients. In logistic regression analysis in High-Altitude Anemia patients with adjustment for age and gender, iron deficiency associated with increased thrombosis history (odds ratio [OR] 6.7, P=0.030) while higher serum transferrin associated with decreased thrombosis history (OR 0.4, P=0.013). In High-Altitude Erythrocytosis patients iron deficiency associated with increased thrombosis history (OR 5.0, P=0.005), but transferrin's association with thrombosis history was not statistically significant (OR 0.8, P=0.52). In anemia and erythrocytosis patients combined, iron deficiency associated with increased thrombosis history (OR 4.6, P=0.0006) while elevated transferrin associated with reduced thrombosis history (OR 0.62, P=0.038).
In individuals with extreme environmental hypoxia, we found no evidence that increasing transferrin is associated with increased thrombosis history, but rather observed a trend to decreased thrombosis history.
Nutritional and Immune-Inflammatory Scoring System for Predicting Prognosis in Patients with Newly Diagnosed Diffuse Large B-Cell Lymphoma
Authors: Peng Yu , Jiang Tingting , Chen Shuang , Tang Xinyi , Zhang Yakun , Ji Dan , Li Liangmei , Ran Longrong , Jun Li , Li Nanjun , Yang Zailin , Liu Yao 
Published: December 2024

Background
Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive non-Hodgkin lymphoma, typically associated with poor prognosis. Current prognostic scoring systems, such as the International Prognostic Index (IPI) and the National Comprehensive Cancer Network (NCCN)-IPI, do not account for the impact of patients' nutritional, immune, and inflammatory responses on their prognosis. To develop a prognostic scoring system for DLBCL patients based on easily obtainable or measurable nutritional, immune, and inflammatory indicators to complement and improve the existing NCCN-IPI and IPI systems.
Methods
A retrospective monocentric analysis of 423 patients who were newly diagnosed DLBCL at Chongqing University Cancer Hospital between January 2020 and September 2023. Relevant patient data were collected from the electronic medical record system, including basic patient characteristics and clinical laboratory results. All eligible patients were randomly divided into training set and validation set at a ratio of 7:3. We used the least absolute shrinkage and selection operator (LASSO) Cox regression model to identify nutritional and immune-inflammatory indicators related to patient prognosis. These indicators were then used to develop the prognostic scoring system. Further analysis was conducted to evaluate the clinical characteristics of this prognostic scoring system and compare it with the IPI and NCCN-IPI.
Results
We developed the Nutritional and Immune-Inflammatory Scoring System (NII), which includes Nutritional Risk Screening (NRS2002), Geriatric Nutritional Risk Index (GNRI), Systemic Immune-Inflammation Index (SII), lactic dehydrogenase to albumin ratio (LAR), β2-microglobulin (β2-MG), CD8+ T cells, natural killer (NK) cells, and CD3+ T cells. A high NII (&gt; 6) effectively identifies high-risk DLBCL patients and serves as an independent prognostic factor beyond other clinical characteristics, IPI, and NCCN-IPI (p &lt; 0.05). DLBCL patients with a high NII (&gt; 6) exhibit significantly adverse clinical features, including advanced age, Ann Arbor stage (III/IV), B symptoms, elevated LDH levels, and higher risk groups according to IPI and NCCN-IPI (p &lt; 0.05). Combining NII with IPI or NCCN-IPI significantly improves the assessment of patient prognosis compared to using IPI or NCCN-IPI alone (p &lt; 0.05).
Conclusion
The Nutritional and Immune-Inflammatory Scoring System (NII) is an effective tool for identifying high-risk DLBCL patients. A high NII (&gt; 6) serves as an independent prognostic factor, revealing significantly adverse clinical features that are not captured by IPI and NCCN-IPI alone. Combining NII with IPI or NCCN-IPI significantly improves the accuracy of patient prognosis assessments compared to using IPI or NCCN-IPI alone.
Venetoclax Plus Dexamethasone As First-Line Treatment for t(11; 14) Light-Chain Amyloidosis: Preliminary Result of a Phase II Prospective, Multicenter, Single-Arm Study
Authors: Shen Kaini , Guan Ai , Wu Yu , Sun Chunyan , Zhong Liye , Luo Jun , Li Jian 
Published: December 2024

Background: Venetoclax has shown promise in providing rapid and high-quality hematologic responses in relapsed/refractory t(11;14) light-chain (AL) amyloidosis cases and offers the convenience of home treatment. To evaluate the efficacy and safety of venetoclax combined with dexamethasone (Ven-D) as an initial treatment for t(11;14) AL amyloidosis patients, we conducted a phase II prospective, multicenter, single-arm study (NCT05996406). Here, we report the preliminary findings.
Method: The study aimed to enroll 36 patients aged 18 or older with newly diagnosed t(11;14) AL amyloidosis. Participants received 12 cycles (28 days per cycle) of Ven-D, consisting of oral venetoclax at 400 mg qd and oral dexamethasone at 20-40 mg qw for the first six cycles, reduced to 10-20 mg for the remaining cycles. Hematologic and organ responses were evaluated at one month, three months and every three months thereafter while on study treatment. Patients who died before the response assessment were categorized under the no-response group. Treatment discontinuation criteria included drug intolerance, unsatisfactory efficacy at the physician's discretion, or disease progression. The primary endpoint was achieving a complete hematologic response (CR) and very good partial response (VGPR) at three months of treatment initiation.
Results: Between September 8, 2023, and June 25, 2024, 36 patients were enrolled, with a median age of 62 years (range 27-75) and predominantly male (80.6%). The distribution of Mayo 2004 stages was as follows: stage I (16.7%), stage II (50.0%), stage IIIA (19.4%), and stage IIIB (13.9%). Heart, kidney, and liver involvement was observed in 80.6%, 50.0%, and 8.3% of patients. By July 25, 2024, all patients had received a median of 5 treatment cycles (range 1-12). Among evaluable patients (n=29), the CR+VGPR rate at three months was 58.6%, with a CR rate of 27.6%. Considering the best hematologic response at any time, the estimate of the CR+VGPR rate was 62.9%, and the CR rate was 37.1%. At six months, cardiac and renal responses were observed in 35.0% and 90.9% of patients, respectively. There were three deaths due to cardiac events and six patients discontinued treatment due to lack of efficacy. Grade 3-4 hematological adverse events included lymphopenia (5.6%) and neutropenia (2.8%), while non-hematological adverse events included edema (2.8%), infection (2.8%) and liver dysfunction (5.6%).
Conclusion: The combination of Ven-D as an initial treatment for t(11;14) AL amyloidosis demonstrates rapid induction of high hematologic responses with a favorable tolerability profile.