bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tranexamic Acid for Trauma Care: An Updated Meta-Analysis of Mortality and Thromboembolic Events in Severely Injured Patients
Authors: Shafique Nouman , Akbar Usman Ali , Umer Ahmed Muaaz , Kumar Besham , Muhibullah Fnu , Siddiqui Fakeha , Vikash Sindhu , Nethagani Sanjana , Rizwan Umer 
Published: December 2023

Introduction : Tranexamic Acid (TXA) is an anti-fibrinolytic agent that inhibits fibrinolysis and prevents blood clot breakdown. Widely used to manage hemorrhage in various clinical scenarios, including trauma, menorrhagia, bleeding in hemophilia, cardiac surgery, and orthopedic surgery, its impact on morbidity and mortality in severely injured patients necessitates an updated systematic review and meta-analysis. Our study aimed to evaluate the association of TXA with mortality and thromboembolic events in trauma patients.
Methods: We conducted a comprehensive literature search on PubMed, EMBASE, CENTRAL, and Google Scholar up to July 2023, focusing on randomized controlled trials (RCTs) involving adult trauma patients receiving Tranexamic Acid (TXA) compared to standard care or placebo. Primary outcomes included mortality rates and thromboembolic event incidence. Statistical analyses used Review Manager Software (RevMan, version 5.3) with the Mantel-Haenszel random-effect model.
Results : A total of 8 randomized controlled trials (RCTs) with 36,416 patients were included in this meta-analysis, comparing Tranexamic Acid (TXA) to control (placebo or standard care). The mean age of the included patients was 39 years. The analysis focused on various patient categories, including multiple trauma versus predominantly traumatic brain injury (TBI) patients, severely injured ( Injury Severity Score ,ISS ≥ 16, massive transfusion requirement, signs of shock) versus non-severely injured patients, blunt versus penetrating versus burn trauma, in-hospital versus prehospital TXA administration, and TXA administration within 3 hours versus beyond 3 hours of injury. The meta-analysis showed that TXA administration was not significantly associated with mortality (odds ratio: 0.98, 95% CI: 0.76 to 1.27, p = 0.89), with moderate heterogeneity observed (I 2 = 56%). However, TXA use demonstrated a significant reduction in the incidence of thromboembolic events (odds ratio: 0.90, 95% CI: 0.84 to 0.95, p = 0.0002), with no significant heterogeneity (I 2 = 0%). (Figure 1 & 2)
Conclusion TXA administration was not significantly associated with mortality in patients with significant trauma; however, it significantly reduced thromboembolic events, suggesting its potential benefit in preventing such complications. Further research is needed to explore its efficacy and safety in specific patient categories and administration settings to optimize its use in trauma care.
Incidence, Clinical Features, and Outcomes of Large Granular Lymphocyte Leukemia
Authors: Budhathoki Pravash , Shah Anish , Karki Ujjwal , Neupane Niraj , Shah Sabita , Kariamanickam Karthickrajkumar 
Published: December 2023

Introduction: -
Large Granular Lymphocyte (LGL) leukemia is a rare and diverse hematologic disorder characterized by the clonal proliferation of large granular lymphocytes in the peripheral blood and bone marrow. Despite its rarity, population-based studies on LGL leukemia remain limited. This study aims to comprehensively analyze clinical characteristics and outcomes among patients with LGL leukemia.
Methods: -
We utilized the Surveillance, Epidemiology, and End Results (SEER) database 17 registry to identify patients diagnosed with large granular lymphocytic leukemia between 2000-2020. Data analysis was conducted using SEER*Stat version 8.4.1.2 and STATA. Univariate survival analysis was done using a Kaplan Meir plot with a log-rank test, and the Cox proportion hazard regression model was used for multivariate survival analysis.
Results: -
We identified a total of 2,589 LGL leukemia cases during the study period. The calculated incidence of LGL leukemia was 0.14 cases per 1,000,000 individuals (range: 0.14 - 0.15). Male patients exhibited a higher incidence rate ratio of 1.19 (95% CI: 1.11 - 1.27, p &lt; 0.01) than females. However, females tended to be diagnosed younger than males (67 vs. 68, p &lt; 0.01). Most cases were observed in the White population (83%) compared to other racial groups. The median age at diagnosis was 67 years (ranging from 7 to 85 years). Patients aged above 70 years showed the highest incidence of LGL leukemia (0.80) in contrast to those aged 45-54 years (0.30) and 55-64 years (0.63). Notably, there was a significant increasing trend in LGL leukemia incidence, with an incidence rate ratio of 13.50 (95% CI: 10.5-17.6, p &lt; 0.001) in the period 2015-2019 compared to 2000-2004.
Approximately 32.7% of patients received chemotherapy; the median time from diagnosis to treatment was one month. The survival rates at 12, 36, and 60 months for LGL leukemia patients were 88.9%, 76.5%, and 66.5%, respectively, with a median follow-up of 40 months. Multivariate analysis revealed that females had a more favorable survival outcome than males (HR: 0.78, 95% CI: - 0.64 - 0.97, p: 0.02). Moreover, patients who underwent chemotherapy exhibited better survival than those who did not (HR: 0.72, 95% CI: 0.56 - 0.93, p: 0.01). Elderly patients above 60 years of age had poorer survival rates (HR: 3.1, 95% CI: 2.34 - 4.01, p &lt; 0.01), and no significant difference in outcomes was observed based on the timing of chemotherapy initiation from the time of diagnosis.
Conclusion: -
This study represents the most extensive and most recent population-based investigation of LGL leukemia. The findings highlight the potential benefits of chemotherapy in improving survival and indicate better outcomes in female patients. Further research is warranted to validate these promising results and gain deeper insights into the management and prognosis of LGL leukemia.
Hypertension and Related-Disorders in Hodgkin Lymphoma Patients Identified from Epic Cosmos System
Authors: Mariano John , Gleber Conrad , Casulo Carla 
Published: December 2023

Recent advancements in Hodgkin lymphoma (HL) treatment have significantly improved disease-free survival rates. However, survivors face a higher burden of long-term comorbidities and non-oncologic mortality compared to their peers. Studying survivorship has been challenging due to the time required for comorbidities to develop, patient loss to follow-up, variable disease-specific treatments, and variations across age groups of survivors. In this context, the Cosmos system offers a validated population-based informatics approach to establishing observational relationships between therapy and longitudinal non-oncologic outcomes, with the potential to enhance clinical care.
Cosmos, a data science tool based on the Epic Electronic Medical Record (EMR) system, utilizes a HIPAA-defined limited centralized data set from various US health care systems. At the time of this submission, the data set encompasses 152,450,619 patients. A query population of 89,963 HL patients with more than one face-to-face encounter within any two-year period during the query interval was established. Validated associated ICD-10 diagnoses were assessed within the Cosmos system.
The query revealed that HL patients had a median age of 56, with a male predominance (51.8%), and 35% were diagnosed between the ages of 15 and 39. Staging information was available for only 10% of patients. The most common comorbid diagnoses defined by ICD-10 were essential hypertension (45.4%), hyperlipidemia (36.1%), anemia (32.1%), GERD (32.1%), shortness of breath (31.4%), fatigue (30.1%), non-HL (30%), cough (26.3%), and anxiety (25.6%).
Further assessment of hypertension and associated disorders was conducted by querying Epic grouper terms in comparison to the general Cosmos population. The HL population had a higher prevalence of hypertension (46.1% vs. 24.5%), chronic kidney disease (14.9% vs. 5%), hypertensive renal disease (10.1% vs. 3.1%), hyperlipidemia (44% vs. 21.1%), coronary artery disease (20.7% vs. 6.2%), ischemic or unspecified stroke (4.4% vs. 1.6%), and myocardial infarction (9.6% vs. 2.8%). Notably, death dates were documented for 12.5% of the HL population (compared to 3% in the general Cosmos population), but cause of death information was limited (0.028%).
EMR informatics presents a powerful tool for rapidly generating real-time observational data, which can inform focused studies and interventions. Such data is crucial for understanding trends in treatment-related morbidity and mortality in diseases like HL, which can impact future health in survivorship. This study suggests that hypertension and related disorders may be more prevalent in the HL population compared to the general Cosmos population, warranting further directed study and validation in the future.
Differential Effect of Transferrin Lobe Iron Occupancy on a Murine Model of Inflammation
Authors: Parrow Nermi L. , George Nisha Ajit , Ali Faris , Wattad Nadia , Guerra Amaliris , Ginzburg Yelena , Rivella Stefano , Fleming Robert E. 
Published: December 2023

Introduction: Iron status is both affected by and a determinant of the inflammatory response. Several lines of evidence support a role for transferrin as a signaling as well as an iron delivery molecule. We previously demonstrated that mice with transferrin mutations that prevent iron binding to the C-lobe of transferrin (C-blocked) have increased red cell production relative to erythropoietin and increased hepcidin expression relative to iron status compared to mice with transferrin mutations that prevent iron binding to the N-lobe of transferrin (N-blocked). Based on these observations, we hypothesize that two forms of transferrin would differentially modulate the hematopoietic and iron distribution changes that occur with inflammation. We explored this hypothesis by comparing the effects of lipopolysaccharide (LPS) administered either acutely or in repeated doses to wild-type, N-lobe blocked, or C-lobe blocked transferrin mutant mice.
Methods: For a model of acute inflammation, 14 day old wild-type (wt), N-blocked and C-blocked Tf mutant mice were treated with 1mg/kg LPS or carrier i.p. and sacrificed 6 hours later. Repeated LPS dosing, seven daily i.p. injections of 0.3 mg/kg LPS or carrier beginning at seven days of age, served as a model of chronic inflammation.
Results: While wild-type and C-blocked mice had the expected hypoferremia in response to acute LPS administration, there was no effect on serum iron in the N-blocked mice. These mice moreover demonstrated an unanticipated increase in liver iron concentrations with LPS. All strains manifested expected increases in liver hepcidin expression; however, these were attenuated in the N-blocked mice relative to the C-blocked. Moreover, N-blocked mice have higher serum C reactive protein concentrations compared to C-blocked and wt mice following acute LPS administration. The elevated Hamp1 expression was not sustained in the chronic model. Although serum iron returned to baseline in wt and C-blocked mice, it remained elevated in N-blocked mice. Hemoglobin concentrations were decreased in all strains after repeated endotoxin dosing; however, C-blocked mice demonstrated higher neutrophil to lymphocyte ratios than wt or N-blocked mice, and increased circulating RBC count relative to WBCs.
Conclusions: We conclude that the specificity of transferrin lobe iron occupancy is an important modulator of the inflammatory response and speculate that this modulation includes an effect on hematopoietic cell lineage determination.
Normative Data of Beta-2-Microglobulin and Plasma Proteins from an Agrarian Indian Community By a Door-to-Door Survey: Results of Simple (IMAGe-002B) Study
Authors: Vashishth Yash , Yanamandra Uday , Bobdey Saurabh , Sharma Vaibhav , Bhatti V K , Muthukrishnan J , Malhotra Pankaj , Nair Velu 
Published: December 2023

Introduction: Most diagnostic laboratories in India follow the reference intervals given in Western literature whose Caucasian reference population is entirely different from the Indian ethnic population (viz., dietary habits, lifestyle, socioeconomic status, ethnicity, and environmental factors).
Objectives: To collate normative data of beta-2-microglobulin (β2M) and plasma proteins from an otherwise healthy population from an agrarian Indian Community. The secondary objectives were to evaluate the correlation of β2M levels with age, gender, and BMI of these individuals.
Methods: A cross-sectional study was conducted in an agrarian village in India with a 24.76Km perimeter and 4588.3 hectares with an 89.2% population coverage for adults (&gt;45y) spending 12096 man-hours. This was a part of SIMPLe (Screening Intervention for Myeloma and Prevention of Lifestyle diseases) study registered vide CTRI/2023/03/051220 after obtaining informed consent. Demographic details, medical history, and blood samples were collected after a thorough medical examination to ascertain the normal health status of the study participants. Hemogram, biochemistry (Liver and renal function tests), β2M, and serum protein electrophoresis (SPEP) were performed in all individuals. Only individuals with normal renal and liver function tests were included in the final analysis. Bivariate analysis (Fit Y by X) was done to study the correlations. Any p value &lt; 0.05 was considered significant. The data was analyzed using JMP ver. 16.0.0.
Results: A total of 850 individuals were included in this community-based door-to-door survey. The mean age of the study population was 57.6±10.5y, with a slight female predominance (56.3%). The distribution of β2M and various plasma proteins is mentioned in Table 1. The β2M significantly differed between males and females (χ 2-8.58; dF-1; p-0.0034). On bivariate analysis, β2M was significantly associated with age (correlation coefficient: 0.31; p&lt;0.0001), and BMI (correlation coefficient -0.07; p-0.023).
Conclusion: The data obtained from our studies would act as the first step in collating normative data for β2M and plasma proteins from Indian community.
Ultra-Low-Dose of Decitabine with Venetoclax As Induction and Consolidation Therapy for Elderly or Frail Newly Diagnosed Acute Myeloid Leukemia and High Risk Myelodysplastic Syndrome Patients
Authors: Zheng Weiyan , Fu Shan , Luo Xuepin , Zhu Yuanyuan , Huang He 
Published: December 2023

Background: Venetoclax with hypomethylating agents is a new standard of care for newly diagnosed (ND) patients with acute myeloid leukemia (AML) who are 75 years or older, or unfit for intensive chemotherapy. Pharmacodynamic studies have suggested superiority of the longer 10-day regimen of decitabine which has shown promising results in high-risk AML in phase 2 trials. We hypothesized that venetoclax with 10-day decitabine may be effective in ND and secondly AML/MDS, particularly for high-risk subgroups.
Methods: We retrospectively analyzed 45 patients with ND AML, secondary AML (sAML), or high-risk MDS who was older than 60 years or unfit for intensive chemotherapy due to frail / due to the COVID-19 pandemic. Patients were required adequate end-organ function. Patients received decitabine (6mg/m2 IV for 10-days) with oral venetoclax (400mg daily for 3 weeks (D10+VEN)) for induction, followed by the same chemo-free regimen for consolidation if patients responsed to induction therapy. The primary efficacy endpoint was overall response rate (ORR). The second endpoint was overall survival (OS) and progress free survival (PFS).
Findings: Between January, 2020 and July , 2023, 45 patients were treated with this regimen, 31 (68.9%) had ND AML, 8 patients (17.8%) had untreated sAML, 6 patients (13.3%) had untreated high-risk MDS. The median age was 65 years (IQR, 59-69) and 26(57.8%) patients had ECOG performance status of 3 or higher. The ORR among all patients was 82.2% and in disease subgroups were: ND AML, 87.1% (27/31) (95% CI 79, 94); untreated sAML, 75% (6/8); untreated high-risk MDS, 66.7%(4/6). According 2022 ELN risk classification by genetics, the ORR in favorable risk patients was 87.5%(7/8), intermediate risk patients was 100%(12/12), adverse risk patients was 72%(18/25). The most common treatment-emergent adverse events included infections with grade 3/4 neutropenia (n=36, 80%) and febrile neutropenia (n=7, 15.6%). There were 2 grade 5 adverse events including one infections with Enterobacter cloacae Bacteremias combined with heart failure because of the shortage of Blood product transfusion during the COVID-19 pandemic, and one case of intracranial hemorrhage related to prolonged grade 3/4 thrombocytopenia. The one year OS of all patients was 71.9%(23/32), and in favorable risk patients was 83.3% (5/6), intermediate risk patients was 72.7%(8/11), adverse risk patients was 73.3%(11/15). The two-year OS of all patients was 58.3%(7/12).
Conclusion: Ultra-low-dose of ten-day decitabine with venetoclax as induction and consolidation chemo-free therapy in elderly or frail newly diagnosed acute myeloid leukemia and high risk myelodysplastic syndrome result in high overall response rate and high 1-year overall survivial.
Venetoclax–based low intensity therapy in molecular failure of NPM1-mutated AML
Authors: Jimenez-Chillon Carlos , Othman Jad , Taussig David , Jimenez-Vicente Carlos , Martinez-Roca Alexandra , Tiong Ing Soo , Jain Manish , Aries James , Cakmak Seda , Knapper Steven , Kristensen Daniel Tuyet , Murthy Vidhya , Galani Joy Zacharoula , Kallmeyer Charlotte , Ngu Loretta , Veale David , Bolam Simon , Orfali Nina , Parker Anne , Manson Cara , Parker Jane , Erblich Thomas , Richardson Deborah , Mokretar Katya , Potter Nicola , Overgaard Ulrik Malthe , Roug Anne Stidsholt , Wei Andrew H. , Esteve Jordi , Jädersten Martin , Russell Nigel , Dillon Richard 
Published: December 2023

Abstract
Molecular failure in NPM1-mutated acute myeloid leukemia (AML) inevitably progresses to frank relapse if untreated. Recently published small case series show that venetoclax combined with low-dose cytarabine or azacitidine can reduce or eliminate measurable residual disease (MRD). Here, we report on an international multicenter cohort of 79 patients treated for molecular failure with venetoclax combinations and report an overall molecular response (≥1-log reduction in MRD) in 66 patients (84%) and MRD negativity in 56 (71%). Eighteen of 79 patients (23%) required hospitalization, and no deaths were reported during treatment. Forty-one patients were bridged to allogeneic transplant with no further therapy, and 25 of 41 were MRD negative assessed by reverse transcription quantitative polymerase chain reaction before transplant. Overall survival (OS) for the whole cohort at 2 years was 67%, event-free survival (EFS) was 45%, and in responding patients, there was no difference in survival in those who received a transplant using time-dependent analysis. Presence of FLT3-ITD mutation was associated with a lower response rate (64 vs 91%; P &lt; .01), worse OS (hazard ratio [HR], 2.50; 95% confidence interval [CI], 1.06-5.86; P = .036), and EFS (HR, 1.87; 95% CI, 1.06-3.28; P = .03). Eighteen of 35 patients who did not undergo transplant became MRD negative and stopped treatment after a median of 10 months, with 2-year molecular relapse free survival of 62% from the end of treatment. Venetoclax–based low intensive chemotherapy is a potentially effective treatment for molecular relapse in NPM1-mutated AML, either as a bridge to transplant or as definitive therapy.
Quantitative proteomics analysis based on data-independent acquisition reveals the effect of Shenling Baizhu powder (SLP) on protein expression in MAFLD rat liver tissue
Authors: Song Sufei , Zheng Jixian , Zhao Dongmei , Zheng Anni , Zhu Ye , Xu Qiuling , Liu Tao 
Published: December 2023

Abstract
Background
Metabolic associated fatty liver disease (MAFLD) has become the most common chronic liver disease worldwide, and it is also a high-risk factor for the development of other metabolic diseases. Shenling Baizhu powder (SLP) is a traditional Chinese herbal formula with good clinical efficacy against MAFLD. However, its molecular mechanism for the treatment of MAFLD is still not fully understood. This study used quantitative proteomics analysis to reveal the SLP action mechanism in the treatment of MAFLD by discovering the effect of SLP on protein expression in the liver tissue of MAFLD rats.

Materials and methods
Q-Orbitrap LC–MS/MS was used to identify the incoming blood compounds of SLP. The 18 SD male rats were randomly divided into 3 groups (n = 6): control group, HFD group and SLP group. The HFD group and SLP group were established as MAFLD rat models by feeding them a high-fat diet for 4 weeks. Afterwards, the SLP group was treated with SLP (10.89 g/kg/d) for 3 weeks. Biochemical parameters and liver pathological status were measured. Rat liver tissue was analyzed using DIA-based quantitative proteomics and the DEPs were validated by western blotting analysis.

Results
A total of 18 active compounds of SLP were identified and isolated to enter the bloodstream. Comparison of DEPs between control group vs. HFD group and HFD group vs. SLP group revealed that SLP restored the expression of 113 DEPs. SLP catalyzes oxidoreductase activity and binding activity on mitochondria and endoplasmic reticulum to promote lipid oxidative catabolism, maintain oxoacid metabolic homeostasis in vivo and mitigate oxidative stress-induced hepatocyte injury. And 52 signaling pathways including PPAR signaling, arachidonic acid metabolism and glycine, serine and threonine metabolism were enriched by KEGG. PPI topology analysis showed that Cyp4a2, Agxt2, Fabp1, Pck1, Acsm3, Aldh1a1, Got1 and Hmgcs2 were the core DEPs. The western blotting analysis verified that SLP was able to reverse the increase in Fabp1 and Hmgcs2 and the decrease in Pck1 induced by HFD, and the results were consistent proteomic data.

Conclusion
SLP ameliorates hepatic steatosis to exert therapeutic effects on MAFLD by inhibiting the expression of lipid synthesis genes and inhibiting lipid peroxidation in mitochondria. This study provides a new idea and basis for the study of SLP in the treatment of MAFLD and provides an experimental basis for the clinical application of SLP.
Association between fatty acid metabolism gene mutations and Mycobacterium tuberculosis transmission revealed by whole genome sequencing
Authors: Li Yameng , Kong Xianglong , Li Yifan , Tao Ningning , Wang Tingting , Li Yingying , Hou Yawei , Zhu Xuehan , Han Qilin , Zhang Yuzhen , An Qiqi , Liu Yao , Li Huaichen 
Published: December 2023

Abstract
Background
Fatty acid metabolism greatly promotes the virulence and pathogenicity of Mycobacterium tuberculosis (M.tb). However, the regulatory mechanism of fatty acid metabolism in M.tb remains to be elucidated, and limited evidence about the effects of gene mutations in fatty acid metabolism on the transmission of M.tb was reported.

Results
Overall, a total of 3193 M.tb isolates were included in the study, of which 1596 (50%) were genomic clustered isolates. Most of the tuberculosis isolates belonged to lineage2(n = 2744,85.93%), followed by lineage4(n = 439,13.75%) and lineage3(n = 10,0.31%).Regression results showed that the mutations of gca (136,605, 317G > C, Arg106Pro; OR, 22.144; 95% CI, 2.591-189.272), ogt(1,477,346, 286G > C ,Gly96Arg; OR, 3.893; 95%CI, 1.432–10.583), and rpsA (1,834,776, 1235 C > T, Ala412Val; OR, 3.674; 95% CI, 1.217–11.091) were significantly associated with clustering; mutations in gca and rpsA were also significantly associated with clustering of lineage2. Mutation in arsA(3,001,498, 885 C > G, Thr295Thr; OR, 6.278; 95% CI, 2.508–15.711) was significantly associated with cross-regional clusters. We also found that 20 mutation sites were positively correlated with cluster size, while 11 fatty acid mutation sites were negatively correlated with cluster size.

Conclusion
Our research results suggested that mutations in genes related to fatty acid metabolism were related to the transmission of M.tb. This research could help in the future control of the transmission of M.tb.