bluuebunny/crossref_metadata_2025_split huggingface dataset:
Variation in ambulance pre-alert process and practice: cross-sectional survey of ambulance clinicians
Authors: Coster Joanne E , Sampson Fiona C , O'Hara Rachel , Long Jaqui , Bell Fiona , Goodacre Steve 
Published: December 2024

BackgroundAmbulance clinicians use pre-alert calls to inform emergency departments (EDs) about the arrival of critically ill patients. However, there is variation in guidance between local ambulance service policies in terms of what should be pre-alerted and how pre-alerts should happen. We conducted a national online survey to understand the use of ambulance pre-alerts and to inform recommendations for practice and guidance.MethodsAmbulance clinicians in England involved in pre-alert decision-making were recruited via ambulance trusts and social media to complete an anonymous online survey conducted during May–July 2023. Quantitative data was analysed descriptively using SPSS (version 28) and free-text responses are reported to illustrate the quantitative findings.ResultsWe included 1298 valid responses from 10 English ambulance services. There was variation in practice at all stages of the pre-alert process, including the reported frequency of pre-alert (7.1% several times a shift, 14.9% once/two times per month). Most respondents reported that pre-alerts were delivered directly to the ED, but 32.8% reported pre-alerting via an ambulance control room. A third of respondents always used mnemonics to guide a pre-alert (eg, ATMIST (Age, Time of Incident, Mechanism of injury, Injuries, Signs, Treatments)), but 10.2% reported not using any fixed format.The type of guidance used to identify patients for pre-alert varied between clinicians and ambulance services, with local ambulance service guidance being most commonly used, and 20% stating they never use national guidelines. Respondents reported variable understanding of appropriate conditions for pre-alert, with paramedic students particularly wanted further guidance on trauma in older patients and medical pre-alerts. 29% of respondents reported receiving specific pre-alert training, while 50% reported never receiving feedback.ConclusionWe identified variation in pre-alert processes and practices that may result in uncertainty and challenges for ambulance clinicians providing time-critical care. Guidance and training on the use of pre-alerts may promote more consistent processes and practices.
Peptide BG From Bitter Gourd (Momordica Charantia) Improves Adjuvant‐Induced Arthritis by Modulating the Necroptosis/Neutrophil Extracellular Traps/Inflammation Axis and the Gut Microbiota
Authors: Han Wenyan , Xu Yanan , Qimuge Suyila , Wang Changshan , Su Xiulan 
Published: December 2024

Background: BG is a novel bioactive peptide derived from bitter gourd (Momordica charantia), known for its anti‐inflammatory and immunomodulatory properties. In the present study, our objective is to investigate the functional roles and mechanisms of BG in the context of rheumatoid arthritis (RA).Methods: A rat model of adjuvant‐induced arthritis (AIA) was established by administering complete Freund’s adjuvant (CFA). The viability of BG‐mediated AIA was evaluated by assessing changes in rat body weight, joint swelling, ankle joint pathology, inflammation, necroptosis, the formation of neutrophil extracellular traps (NETs), and gut microbiota.Results: The results of the study showed that peptide BG was effective in improving weight loss, joint swelling, serum IgM‐rheumatoid factor (IgM‐RF) level, and pathological injury of ankle joint in rats with AIA. BG administration resulted in a decrease in erythrocyte sedimentation rate, serum C‐reactive protein (CRP), and inflammatory factor (interferon‐γ (IFN‐γ), interleukin‐1β (IL‐1β), and tumor necrosis factor‐α (TNF‐α)) in AIA rats. Additionally, the administration of CFA resulted in an increase in the protein levels of myeloperoxidase (MPO), neutrophil elastase (NE), citrullinated histone H3 (CitH3), peptidyl arginine deiminase 4 (PAD4), p‐mixed lineage kinase domain‐like (p‐MLKL), and cleaved caspase 8. However, this increase was found to be inhibited by BG treatment. Furthermore, it has been found that peptide BG possesses the capacity to regulate the species composition structure of the intestinal microbiota, thereby, facilitating the reestablishment of microbial diversity and equilibrium.Conclusion: Peptide BG has demonstrated efficacy in ameliorating AIA through its regulation of the necroptosis/NETs/inflammation axis and the gut microbiota. This finding underscores the potential of BG as a promising therapeutic intervention for RA.
Producing Ephemeral City during the Pandemic: Healthcare and Cultural Continuity at Data Saheb’s Urs in Lahore (Pakistan)
Authors: Hasnain Sajjad 
Published: December 2024

Abstract
This article explores frictions between state-led pandemic measures and public aspirations that sought religious-cultural continuity during covid-19 crisis. Through the case of annual festival at Data Saheb’s shrine (Lahore), it shows that devotees built an ephemeral city for three-day celebrations as a way of asserting their commitment to a centuries old tradition. It is argued that the cultural continuities of devotion to the city saint appeared to be flowing undeterred in the face of healthcare initiatives – making the shrine a microcosm that reflected flexibilities and lapses at the national level vis-à-vis pandemic governance. While elsewhere that might be seen as a case of (in)effective public health administration, at the shrine, it unearthed power equation between the religious actors and the state in Pakistan manifesting itself since Data Saheb’s demise in 12th century around political legitimation, public morality, patronage of shrines and control of religious actors in local politics.
Potent Effects of Lenalidomide-Conjugated Anti-CD38 Antibody-Drug Conjugate (TE-1146) on Multiple Myeloma Cells Isolated from Patients
Authors: Jiang Jing Gu , Lin Shih-Chiang , Cheng Shih-Syuan , Yu Yueh-Hsiang , Chang Tse Wen , Chu Hsing-Mao , Yu Yuan-Bin 
Published: December 2024

Background: Despite available therapies such as proteasome inhibitors, antibodies, and immunomodulators, multiple myeloma (MM) remains incurable, with patients often experiencing relapses and severe side effects. To address this issue, we employed a proprietary HighDAR platform and developed TE-1146, which is a site-specific lenalidomide (Len)-conjugated antibody-drug conjugate (ADC) targeting CD38 on MM cells. TE-1146 utilizes cleavable linkers recognized by lysosomal cathepsin B and carries six Len molecules. Studies have shown that TE-1146 has stronger direct cytotoxicity than the combination of daratumumab (Dara) and Len, while maintaining similar Fc-mediated effects such as antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and antibody-dependent cellular phagocytosis (ADCP). Additionally, TE-1146 has a long half-life (t1/2: 11.1 days) in healthy mice and demonstrates superior anti-tumor efficacy in human MM cell line-derived xenograft mouse models compared to the Dara and Len combination.
Methods: This study evaluates the efficacy of TE-1146 using human MM cells isolated from bone marrow samples obtained from patients between July 2023 and May 2024. Fifteen samples were categorized into three subgroups (5 samples each): (1) from treatment-naïve patients, (2) from relapsed patients without prior Dara/Len treatments, and (3) from relapsed patients with prior Dara/Len treatments. Isolated MM cells were treated with TE-1146 or Dara/Len combination, and cytotoxicity was assessed.
Results: Of the 15 screened samples, 14 were eligible for the study, all expressing both CD138 and CD38. In subgroup 1 (treatment-naïve patients), among 5 eligible samples, TE-1146 achieved a 100% cytotoxic response with a mean IC50 value of 0.05 nM. In subgroup 2 (patients who relapsed after bortezomib, thalidomide, and dexamethasone [VTD] regimens, without prior Dara/Len treatment), all 4 eligible samples exhibited a 100% cytotoxic response with a mean IC50 value of 0.02 nM. In subgroup 3 (relapsed, with prior Dara/Len treatment, 5 eligible samples), one sample responded to TE-1146 treatment with an IC50 value of 1.96 nM. In subgroups 1 and 2, TE-1146 exhibited at least 100-fold greater MM cell lysis compared to Dara, Len, or their combination, based on IC50 values. Nevertheless, in subgroup 3, TE-1146 showed limited efficacy, likely due to developed resistance to Dara or Len.
Conclusion: This study demonstrates that TE-1146 enhanced direct cytotoxicity, significantly improving efficacy over the Dara/Len combination while potentially reducing the required dosage and associated side effects of Len. These results support further development and clinical evaluation of TE-1146 ADC as a promising treatment for MM.
UBE2E3 Supports Survival of Leukemia Stem Cells By Regulation of Polycomb Repression Complex (PRC) 1.1
Authors: Miller Vika , Hija Ayat , Abdal-Rhaman Mohamed , Gross Even-Zohar Noa , Saltsman Michal , Botham Aaron , Haran Arnon , Aumann Shlomzion , Vainstein Vladimir , Gatt Moshe E , Raught Brian , Schimmer Aaron D , Nachmias Boaz 
Published: December 2024

AML cells are arranged in a hierarchy with leukemia stem cells giving rise to a more differentiated bulk leukemia cells. The determinants that support stemness are still not completely understood.
Recently, we identified importin 11 (IPO11), a nuclear transport receptor, as a regulator of stemness in AML. To identify cargo protein imported into the nucleus by IPO11, we conducted a BioID-mass spectrometry screen. Through this screen, we discovered that IPO11 interacts with the E2 ligase, UBE2E3 to regulate its nuclear localization. The importance of UBE2E3 in AML and its role in leukemia stemness is currently unknown. Therefore, we focused our investigation on UBE2E3.
To understand the role of UBE2E3 in AML and leukemia stem cells, we knocked down UBE2E3 in AML cell lines. Silencing of UBE2E3 shifted the transcriptomic signature away from leukemia stem cells and hematopoietic stem cell progenitors toward a more differentiated and mature signature: LSC+ vs. LSC- (FDR ≤0.01, GSE76008) and progenitor/stem vs. myeloid cluster (FDR ≤ 0.01, TCGA-AML). Moreover, knockdown of UBE2E3 in OCI-AML2, NB4 and K562 AML cells reduced growth and viability of by 60-70%, as well as reduced clonogenic growth, consistent with an effect on leukemia initiating cells.
To investigate how UBE2E3 regulates leukemic stemness, we performed a BioID mass spectrometry screen for proteins that interact with UBE2E3. Through this screen, we discovered that UBE2E3 interacted with poly-comb repression complex (PRC) proteins, including four core components of a variant of PRC-1, designated PRC1.1, KDM2B, BCOR, RING1 and PCGF1. The PRC mediates epigenetic transcriptional repression, governing key cellular processes, including proliferation and differentiation. Previous work has shown that PRC1.1 control specific genes required for leukemic cell viability. Knockdown of UBE2E3 decreased expression of known PRC 1.1 target genes specific for AML (FDR ≤0.01, GSE54580), such as PKM, MAP3K6 and ERCC1, demonstrating that UBE2E3 positively regulates PRC1.1 activity.
In summary, we identified UBE2E3 as a novel regulator of non-canonical PRC 1.1 complex in AML and through that mechanism a positive regulator of leukemia stemness. Thus, we identified UBE2E3 as a possible novel target in AML.
Correlation between Familial Waldenström Macroglobulinemia Clusters Withclinical Features, Complications, and Outcomes in 1000 Patients: A Single-Center Retrospective Cohort Study
Authors: Ramirez Andres , Castillo Jorge J. , Tsakmaklis Nickolas , Hunter Zachary R , Guerrera Maria Luisa , Flynn Catherine A. , Sarosiek Shayna R , Treon Steven P. 
Published: December 2024

Context: Waldenström macroglobulinemia (WM) is a rare type of B-cell lymphoma, with around 20% of patients having a family history of blood malignancies. However, most data about family history are derived from clinical databases with scarce information regarding clinical features, complications, and treatment outcomes among different family groups.
Objective: To determine the relationship between family history, presenting characteristics, complications, and treatment outcomes of patients with WM.
Design, Participants, and Setting: This retrospective study examines family history and clinical data from 1000 adult patients with a clinicopathological diagnosis of WM evaluated at our institution between 2000 and 2022. Patients were followed up until December 2023.
Main Outcome Measures: The primary outcome was to correlate clinical features at the time of diagnosis (sex, age, adenopathy, splenomegaly, hemoglobin, platelets, LDH, albumin, beta-2-microglobulin, IgM, light chain restriction, % bone marrow involvement, MYD88 and CXCR4 mutational status), complications at any time during the disease course (Bing-Neel syndrome, cryoglobulinemia, cold-agglutinin syndrome, malignant pleural effusions, renal involvement, DLBCL transformation, AL amyloidosis, and WM-attributed neuropathy), prevalence of family history (WM, other B-cell, non-B-cell, and sporadic) and treatment outcomes (treatment status, overall survival). Chi-square test and logistic regression models were fitted to evaluate between variables. Cox proportional-hazard regression models were fitted to evaluate survival prognostic factors.
Results: The median follow-up time from diagnosis was 13 years (95% CI, 9.66-16.59). We found that compared with sporadic WM, patients with a family history of WM were more likely women (34% vs 50%; P&lt;0.01). Patients with familial WM showed increased odds of developing Bing-Neel syndrome (OR 5.6; 95% CI, 2.1-14.4; P&lt;0.01) and cryoglobulinemia (OR 3.1; 95% CI, 1.4-7.0; P=0.01) but less likely to develop neuropathy (OR 0.38; 95% CI, 0.2-0.8; P=0.01). In multivariate Cox regression analyses, no significant difference in excess mortality was detected in patients with family history of WM (HR, 1.1; 95% CI, 0.92-1.31; P=0.3).
Conclusion: Our study suggests that patients with a family history of WM are more likely women, have higher odds of cryoglobulinemia and Bing-Neel syndrome, and lower odds of neuropathy. However, no excess mortality was observed.
Impact of Protein Energy Malnutrition on Hospitalized Patients with Amyloidosis: A United States Population-Based Cohort Study
Authors: Arya Yajur , Syal Arshi , Jones Colton Frisco , Byfield Karecia , Casipit Bruce Adrian , Dourado Claudia , Varadi Gabor 
Published: December 2024

Background
Amyloidosis can affect virtually any organ system and lead to a multitude of clinical manifestations. Patients with amyloidosis tend to have varying degrees of protein energy malnutrition (PEM) due to multiple reasons, including cachexia, sarcopenia, and systemic involvement. End organ damage, including renal failure, heavy proteinuria, and malabsorption due to gastrointestinal involvement, further complicates the clinical picture. The impact of PEM on clinical outcomes in this subgroup needs further exploration.
Methods
We utilized the 2020 National Inpatient Sample (NIS) Database in conducting this retrospective cohort study. We identified patients with amyloidosis and PEM using appropriate ICD-10 diagnostic codes. We stratified patients with amyloidosis based on the presence or absence of PEM. A survey multivariable logistic and linear regression analysis was used to calculate adjusted odds ratios (ORs) for the primary and secondary outcomes. A p value of &lt;0.05 was considered statistically significant. The aim of this study was to investigate the impact of PEM on in-hospital mortality, hospital length of stay (LOS), and total hospitalization charges among hospitalized patients with amyloidosis.
Results
We identified a total of 3525 hospitalized patients with amyloidosis, of which 12.48% (440/3525) had comorbid PEM. The overall in-hospital mortality among patients with amyloidosis was 5.39% (190/3525). Among those with concomitant PEM, the mortality rate was significantly higher at 12.50% (55/440, p=0.001). Utilizing a stepwise survey multivariable logistic regression model that adjusted for patient and hospital level confounders, PEM was found to be an independent predictor of increased in-hospital mortality (adjusted OR 2.69; 95% (confidence interval [CI] 1.23-5.85; p=0.013), longer LOS (coefficient 3.09; CI 0.12-6.06; p=0.041), higher total hospitalization charges ($59817; [CI] $8531-$111104; p=0.022), and increased need for mechanical ventilation (adjusted OR 2.21; CI 1.00-4.86; p=0.049).
Conclusion
Our analysis demonstrated that PEM was widely prevalent in hospitalized patients with amyloidosis. It was associated with significantly worsened in-hospital mortality, longer LOS, total cost of healthcare utilization, and increased need for mechanical ventilation. Efforts should be made to promote nutritional assessment and screening mechanisms with the aim to include early nutritional support as indicated. Further prospective studies with larger sample size are warranted to better understand these associations.
Targeting Druggabble Long Non-Coding RNA MALAT1: Epigenetic Regulation of CD38 and Energy Metabolism in Multiple Myeloma
Authors: Cho Shih-Feng , Chang Wen-Hsin , Liao Wei-Ting , Yeh Tsung-Jang , Wang Hui-Ching , Du Jeng-Shiun , Hsu Chin-Mu , Hsiao Hui-Hua , Liu YI-Chang 
Published: December 2024

Multiple myeloma (MM), the second most common hematologic malignancy, exhibits complex genetic and epigenetic abnormalities in its pathogenesis. Long non-coding RNA (lncRNA), defined as non-coding transcripts of more than 200 nucleotides, has been shown to play a crucial role in various critical cellular functions, including those related to malignant diseases. The lncRNA, metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), was found to be upregulated in both newly diagnosed and relapsed MM, indicating its potential oncogenic role. Previous studies also revealed therapeutic targeting MALAT exhibited a significant anti-MM effect. However, the specific mechanisms by which MALAT1 contributes to MM pathogenesis remain to be elucidated.
This study aims to investigate the role of this druggable lncRNA, MALAT1, in the development of MM. Initially, MALAT1 was overexpressed in MM cells, and its expression, along with CD38, was further upregulated in lenalidomide-resistant MM cell lines. Knocking down MALAT1 using antisense oligonucleotides (ASO) significantly decreased MM cell proliferation/viability in both lenalidomide-sensitive and resistant cells. RNAseq-based transcriptome profiles showed that genes related to the oxidative phosphorylation (OXPHOS) pathway were significantly down-regulated following MALAT1 knockdown. Downregulation of MALAT1 further reduced adenosine triphosphate (ATP) levels and elevated the generation of reactive oxygen species (ROS), suggesting those alterations in energy metabolism and the oxidative stress response in MM cells resulted in decreased cell viability. Furthermore, using a ChIP-PCR assay, MALAT1 epigenetically modulated CD38 expression via H3K27me3 modification, involving the polycomb repressive complex 2 (PRC2) complexes with H3K27 methyltransferase EZH2 and EED. Taken together, targeting the druggable lncRNA MALAT1 suppresses MM cell growth, reduces CD38 expression through epigenetic regulation by the PRC2 complexes, and has potential applications in treating lenalidomide resistance in MM.
Impact of Protein Energy Malnutrition on Hospitalized Patients with Chronic Myeloid Leukemia: A United States Population-Based Cohort Study
Authors: Arya Yajur , Syal Arshi , Egert Daniel , Casipit Bruce Adrian , Dourado Claudia , Leighton John Charles 
Published: December 2024

Background
Advances in chemotherapeutics and newer TKIs (tyrosine kinase inhibitors) have increased survival in patients with chronic myeloid leukemia (CML). With prolonged survival, these patients are often predisposed to comorbidities affecting their quality of life. Patients with CML suffer from varying degrees of protein-energy malnutrition (PEM) due to multiple factors, including cachexia, sarcopenia, and adverse effects of chemotherapeutics. However, the impact of PEM on outcomes among patients with CML needs further exploration.
Methods
We used the 2020 National Inpatient Sample (NIS) Database to conduct this retrospective cohort study. We identified patients with CML and PEM using appropriate ICD-10 diagnostic codes. We stratified patients with CML based on the presence or absence of PEM. A survey multivariable logistic and linear regression analysis was used to calculate adjusted odds ratios (ORs) for the primary and secondary outcomes. A p-value of &lt;0.05 was considered statistically significant. This study aimed to investigate the impact of PEM on in-hospital mortality, hospital length of stay (LOS), and total hospitalization charges among hospitalized patients with CML.
Results
We identified a total of 3845 hospitalized patients with CML, of which 10.14% (390/3845) had comorbid PEM. The overall in-hospital mortality among patients with CML was 6.38% (245/3845). Among those with concomitant PEM, the mortality rate was significantly higher at 14.10% (55/390, p=0.003). Utilizing a stepwise survey multivariable logistic regression model that adjusted for patient and hospital level confounders, PEM was found to be an independent predictor of increased in-hospital mortality (adjusted OR 2.72; 95% (confidence interval [CI] 1.27-5.83; p=0.010), longer LOS (coefficient 11.58; CI 6.60-16.56; p=0.001), higher total hospitalization charges ($247587; CI $53783-$441391; p=0.012), and increased need for mechanical ventilation (adjusted OR 4.71; CI 1.68-13.15; p=0.003).
Conclusion
Our analysis demonstrated that PEM was widely prevalent in hospitalized patients with CML. It was associated with significantly worsened in-hospital mortality, longer LOS, total cost of healthcare utilization, and increased need for mechanical ventilation. Efforts should be made to promote nutritional assessment and screening mechanisms to include early nutritional support as indicated. Further prospective studies with larger sample sizes are warranted to understand these associations better.
Maternal Death and Postpartum Death in Maputo Mozambique - a Retrospective Autopsy Study
Authors: Emenalom Esther Chioma , Glenzer Michael , Correia Momade , Nhantumbo Virgilio , Songolo Tosha , Luis Elvira , Silva Patricia , von Drygalski Annette 
Published: December 2024

Introduction
Maternal mortality (MM) in Sub-Saharan Africa is ≈100-fold higher compared to developed countries. Postpartum hemorrhage (PPH) is estimated to cause 30-50% of deaths.
Aim
To determine the direct contribution of PPH to MM in Mozambique.
Methods
Analysis of autopsy reports of pregnant women who died at Hospital Central Maputo (HCM) between 01/2018 and 01/2022. Extracted data included age, labs and vitals on admission, delivery characteristics, HIV status, and causes of death. Direct causes of MM were split into 5 classifications: PPH, hypertensive diseases, indirect, infection/sepsis, and others.
Results
Based on known mortality rates ≈200 autopsy reports were expected for analysis, but only 64 were available; 8 were excluded for prepartum death. PPH occurred in 22/56 women (39.3%) and was the direct cause of death for 17/56 (30.3%). Figure 1 shows the proportion of direct causes of peri/postpartum death, whereby PPH and hypertensive diseases (28.6%) caused ≈2/3rd of deaths. Labs on admission were available for 39 women. Women who later experienced PPH had lower median hemoglobin (8.6 vs 10 g/dL, p=0.046) and platelets (127,500 vs. 187,000/uL, p=0.039) compared to those who did not.
Conclusion
PPH occurred in ≈40% of dying pregnant women and was documented as the direct cause of death in almost all, with more anemia and thrombocytopenia on admission. Difficulties to locate autopsy reports, and the limited availability of tranexamic acid and blood products reveal the need for infrastructural support, prospective studies, and PPH prevention/intervention protocols to effectively reduce maternal mortality in Sub-Saharan Africa.