bluuebunny/crossref_metadata_2025_split huggingface dataset:
Platelet to Lymphocyte Ratio (PLR) As a Marker for Aortic Stenosis Development in a Mouse Model: Relationship to Platelet TGFβ1
Authors: Subramani Kumar , Afzal Tayyab , Babii Denys , Word Trevor , Ahamed Jasimuddin 
Published: December 2024

Objective: Aortic stenosis (AS) is an age-related degenerative valvular disease that can lead to heart failure and sudden death. There is no biomarker for early detection of AS. However, an elevated neutrophil-to-lymphocyte ratio (NLR), reflective of systemic inflammation, is associated with higher mortality in cardiovascular disease, including AS and, recently, the platelet-to-lymphocyte ratio (PLR) was proposed as an additional inflammatory biomarker linked to AS. We have shown that platelet-derived TGF-β1 contributes to AS progression in LDLR-/-ApoB100/100 (LA100) mice, a model that simulates human AS valve pathology. We now evaluate PLR, along with NLR and plasma TGF-β1 levels, as possible correlates of AS progression in this model.
Methods: PLR, NLR, and plasma TGF-β1 were measured in control C57Bl/6 mice and LA100 mice before AS development (2-3 months of age), at the point of moderate AS (10 months of age), and upon development of severe AS (22 months of age). LA100 mice with depletion of TGF-β1 in platelets (LA100-PF4CreTgfb1flox/flox) and LA100 mice treated with low dose galunisertib, an inhibitor of the TGFβ-I receptor kinase, were similarly assessed at 22 months of age.
Results: PLR was significantly higher in mice with severe and moderate AS vs. control LA100 mice (192 ± 49, p&lt;0.01, 249 ± 63 vs. 503 ±139, p=0.009, respectively). NLR was also increased in LA100 vs. control mice (n=12; p&lt;0.01). Total TGF-β1 plasma levels were significantly higher in aged LA100 mice (n=21; 22 months) than in age-matched control C57Bl/6 mice (22 months; p&lt;0.0001). Plasma TGF-β1 levels correlated with both PLR (R=0.26; p=0.020) and NLR (R=0.6, p=&lt;0.001) in LA100 mice, but not in C57Bl/6 mice. Increased PLR and NLR negatively correlated with decreased fractional valve opening, a measure of AS progression, in LA100 mice (p&lt;0.05 for both). To assess the role of platelet-derived TGF-β1 in influencing PLR, we utilized LA100 mice deficient in platelet TGF-β1 (LA100-PF4CreTgfb1flox/flox). They were partially protected from developing AS at 22 months, despite having higher PLR than control LA100 mice at 22 months of age (735 ± 245 vs. 503 ± 139). Moreover, treatment of LA100 mice with low dose galunisertib, was associated with a higher PLR (192 ± 49 vs. 671 ± 290; p&lt;0.05), but a reduced NLR (p=0.03), compared to vehicle-treated control mice.
Conclusions: 1. Increased PLR, NLR, and plasma TGF-β1 levels are surrogate markers of AS progression in a robust mouse model that simulates human AS pathology. 2. Demonstration of higher PLR in mice with altered TGF-β1, via either platelet-specific TGF-β1 depletion or treatment with galunisertib, along with finding a lower NLR in the latter, warrants further study into the mechanism by which PLR may serve as a prognostic marker for AS progression apart from inflammation.
Type B Lactic Acidosis, an Unusual but Important Marker for Diagnosis of Hematologic Malignancy
Authors: Teibel Zachary Raphael , Arora Sahej , Silver Stephen , Anderson Nevin , Sbenghe Maria 
Published: December 2024

ABSTRACT
Introduction:
Lactic Acid is a byproduct of the normal physiologic processes present in the human body. However, elevated lactic acid in the body, or lactic acidosis, can be a key finding in diseased states as well. Malignancies, especially hematological, are a rare but important cause of lactic acidosis without systemic hypoperfusion, with resolution being directly related to the treatment of the culprit malignancy.
Case:
A 50-year-old male presented to the ED and was diagnosed with acute pancreatitis based on symptoms, lipase levels, and imaging findings. He was found to have leukocytosis and anion gap metabolic acidosis with elevated lactic acid and beta-hydroxybutyrate. He was treated with IV fluids with resolution of all metabolic parameters except lactic acidosis and new pancytopenia. A bone marrow biopsy was performed outpatient due to persistent pancytopenia and lactic acidosis and found to be consistent with B-Cell Acute Lymphoblastic Leukemia. Initiation of chemotherapy normalized lactic acid levels within 5 days.
Discussion:
Lactic Acidosis is a common marker of systemic hypoperfusion, but it can rarely occur in the absence of it, especially in malignancies. One mechanism for this is the “Warburg phenomenon” and another could be Riboflavin/Thiamine deficiency. Patients may have potentially long-standing lactic acidosis, and it may be the initial presentation of malignancy, like in our patient. Treatment of underlying cancer resolves this Type B lactic acidosis.
Conclusion:
Lactic Acidosis in an otherwise vitally stable patient with deranged cell counts should raise concern for Type B Lactic acidosis due to possible hematologic malignancy.
A Rare Case of Ectopic Splenic Transplantation in a 16 Year Old with Hereditary Spherocytosis
Authors: Mehta Prutha , Zhao Xiaofeng , Presenza Thomas , Ahmed Rafat 
Published: December 2024

Background: Hereditary Spherocytosis is a well known cause of hemolytic anemia. Splenectomy is indicated in patients who are on chronic transfusions to decrease the ongoing hemolysis. Transplantation of ectopic splenic tissue after splenectomy, although rare, is possible. There has been 1 such documented case report in the adult population, but none in the pediatric population. Clinical symptoms are uncommon, however, can include vague abdominal pain, nausea, vomiting, and organomegaly. Given its proximity to surrounding structures and organs, extra splenic tissue is often mistaken as gallstones, pancreatic masses, lymphomas, neuroendocrine tumors, and even hepatocellular carcinoma. It is understood that in the presence of trauma, ectopic splenic tissue is transplanted into the surrounding parenchyma, thereby allowing its regeneration. However, the etiology of ectopic splenic tissue regeneration in the absence of trauma, such as in this case, has never been reported.
Objective: We report a 16 year old female with a history of hereditary spherocytosis s/p splenectomy who presented with 2 years of intermittent, dull, non radiating RUQ abdominal and midsternal pain. RUQ ultrasound revealed multiple progressively increasing masses in the hepatic and biliary regions. Further characterization on MRI of the abdomen and pelvis revealed 4 large echogenic hepatic lesions and multiple small echogenic lesions in the gallbladder concerning for hepatocellular carcinoma. Core needle biopsy of the lesion was indicated.
Design/Methods: Chart review was performed through the electronic medical record to obtain information about the patient and case.
Results: Core needle biopsy of the hepatic lesion was consistent with spleen tissue; no hepatocytes present; no evidence of carcinoma. The findings are consistent with splenosis or overgrowth of ectopic spleen tissue. A scintigraphy with sensitive heat-denatured technetium-99m-labeled red blood cells is recommended to evaluate other hepatic masses.
Conclusion(s): Transplantation of ectopic splenic tissue in a patient who has undergone total splenectomy is an extremely rare finding in pediatric patients.
Real-World Experience of Efficacy and Toxicity Issues of Inotuzumab Ozogamicin in Adult Patients with Relapsed or Refractory Acute Lymphoblastic Leukemia
Authors: Yoon Jae-Ho , Kwag Daehun , Min Gi June , Park Sung-Soo , Park Silvia , Lee Sung-Eun , Cho Byung-Sik , Eom Ki-Seong , Kim Yoo-Jin , Kim Hee-Je , Min Chang-Ki , Cho Seok-Goo , Lee Seok 
Published: December 2024

Background: In adult patients with relapsed or refractory (R/R) B-cell precursor acute lymphoblastic leukemia (BCP-ALL), CR rates are low and survival outcomes are very poor. For effective salvage therapy and allogeneic hematopoietic cell transplantation (allo-HCT) in remission, inotuzumab ozogamicin (INO) or blinatumomab (BLIN) have been introduced and revealed their efficacy in clinical trials. We analyzed the treatment outcomes of INO for R/R BCP-ALL patients.
Methods: One hundred patients with R/R BCP-ALL (Ph-positive 25, Ph-negative 75) were treated with a median 2 cycles (range: 1-5) of INO. We applied weekly INO with a dosage of 0.8mg/BSA for first week followed by 0.5mg/BSA for second and third week. For second cycle, we applied 0.5mg/BSA of weekly INO for 3 weeks in patients with complete remission (CR) after first cycle. For post-remission treatment, allo-HCT was planned for all patients.
Results: At the time of INO salvage treatment, 7 (7.0%) were primary refractory (4 BLIN-failure), 36 (36.0%) had relapsed during/after consolidation chemotherapy (23 BLIN-failure), and 57 (57.0%) had relapsed after first (n=47) or second (n=10) previous allo-HCT (23 BLIN-failure). At the time of relapse, bone marrow relapse (BMR) alone was observed in 61 (61.0%) and isolated extramedullary relapse (EMR) in 11 (11.0%), and both BMR+EMR in 28 (28.0%). At the end of first INO cycle, overall response was achieved in 60 (60.0%) patients (57.1% for primary refractory, 61.7% for early relapse &lt; 12 months, and 57.6% for later relapse) and 7 of them underwent allo-HCT. We observed 12 (12.0%) early deaths, 28 non-responders, and 4 of them discontinued INO due to VOD/SOS and infectious complications. At the end of second INO cycle, best response was observed in 67 (67.0%) with MRD response of 63.1% and among them, 39 (58.2%) underwent allo-HCT. Among the rest 28 responders, 9 died in CR (2 VOD/SOS, 7 sepsis), 16 relapsed, and 3 are alive in CR after INO consolidation. Follow-up duration was median 24 months (range 8.5-53.5), and 2-year OS was 20.4%, and patients treated with allo-HCT showed 37.7% of 1-year OS.
Conclusion: Our data suggested that INO can be a feasible choice for salvage for adults with R/R BCP-ALL which showed a good CR rate. However, we experienced unexpectedly high regimen-related mortality caused by hepatotoxicity and infectious complications or thrombocytopenia due to marrow suppression. Risk-adapted dose adjustment or patient selection for INO are important for better treatment outcomes.
Detection of M-Protein in Transplant-Ineligible Multiple Myeloma Patients on Daratumumab Using Liquid Chromatography Quadruple Time of Flight Mass Spectrometry
Authors: Balta Kaan Yusuf , Nicholas Matthew , Strelau Matthew , Phua Chai Wye W. 
Published: December 2024

Background
Given the recent transition to novel front-line combinations capable of achieving a deeper response, the incorporation of measurable residual disease (MRD) into the response criteria for multiple myeloma (MM) could allow for better prognostication and potentially introduces MRD-adaptive treatment approaches. Liquid chromatography high-resolution mass spectrometry (LC-HRMS) is a powerful analytical tool that combines physical separation with high-resolution mass spectrometric detection. Mass spectrometry (MS) has emerged as a new diagnostic platform for monitoring M-proteins in MM, offering enhanced sensitivity for detecting M-proteins from peripheral blood compared to conventional serum protein electrophoresis/immunofixation analysis. Its utility has been endorsed in the 2021 IMWG guidelines.
Methods
Peripheral blood samples from MM patients were collected and used for validation of the MS. Samples were prepared in a multistep analytical process involving sample preparation by affinity purification targeting the conserved regions of immunoglobulins G, A, M, kappa, and lambda to enrich immunoglobulins and wash away serum proteins. Samples were analyzed on an Agilent 6545XT AdvanceBio LC/Q-TOF. M-proteins were identified by intact light chain masses above the polyclonal background. Samples were analyzed and compared to immunofixation electrophoresis (IFE) and flow cytometry (FC) (preliminary 10-4, forthcoming 10-5). Results were grouped into 4 categories: IFE+/QTOF+, IFE+/QTOF-, IFE-/QTOF+, IFE-/QTOF-. Limit of detection (LOD) studies were conducted by spiking IgG-kappa biologics into serum for both LC/Q-TOF and IFE.
Active and ongoing results
The LC/Q-TOF was able to isotype M-proteins similarly to IFE but with a mass accuracy approximately 1 Da. The LC/Q-TOF LOD was ~35 mg/L. 183 patient serum samples were analyzed. 134 were QTOF+/IFE+, 23 were QTOF-/IFE-, 23 were QTOF+/IFE-, and 3 were QTOF-/IFE+. When QTOF+/IFE- results were excluded due to the improved sensitivity of the LC/Q-TOF method, the concordance of LC/Q-TOF with IFE was ~98%.
Conclusions
Accurate mass determination of the M-protein intact light chain can readily differentiate daratumumab from IgG-kappa M-proteins. Excluding QTOF+/IFE-, the concordance rate was 98% between IFE and QTOF. QTOF demonstrated a LOD for IgG-kappa ~ 35 mg/L which is ~ 5-10x lower than most IFE estimated LODs. Future samples will compare QTOF to MRD assessments using next generation flow cytometry at a detection level of 10-5.
Jobelyn, a Sorghum Bicolor Exract-Based Oral Supplement Reduces Oxidative Stress in School Aged Children with Sickle Cell Disease
Authors: Diaku-Akinwumi Ijeoma Nnenna , Olajide Deborah , Adekunle Motunrayo B , Adebayo Adekunle B , Bamiro Saka , Ofakunrin Akinyemi O.D. , Ajonuma Louis C 
Published: December 2024

Introduction:
Sickle cell disease (SCD) is highly prevalent in Sub-Saharan Africa, contributing to 16% of mortality in Nigerian and Ghanaian children under 6 years of age. School-aged children with SCD experience recurrent illness, hospitalization, and disability due to complications. Oxidative stress contributes significantly to SCD pathophysiology. This study investigated Jobelyn®, a sorghum bicolor-based herbal supplement, for its effect on oxidative stress markers in SCD children. Jobelyn is available over the counter and is use by people living with SCD in Nigeria.
Methods:
This non-randomized, quasi-experimental study included 87 Jobelyn-naïve children with SCD (aged 5-17 years). Ethics approval was granted by the Lagos State University Teaching Hospital health research ethics committee. Parents and participants gave written consent and assent. Demographic data, full blood counts, and oxidative stress markers (Glutathione, superoxide dismutase, catalase, and malondialdehyde) were measured at baseline, 6 weeks, and 12 weeks after commencing Jobelyn supplementation. Children receiving hydroxyurea were not excluded.
Results:
Significant increases in Glutathione levels (p&lt;0.0001) and decreases in superoxide dismutase, catalase, and malondialdehyde levels (p&lt;0.0001) were observed at 6 and 12 weeks. Hemoglobin concentrations rose significantly (p&lt;0.001) at 6 weeks, while white cell counts fell below steady state values (p&lt;0.001). Both hydroxyurea-naïve and the near equal number of hydroxyurea-treated children all responded with statistically significant changes in oxidative stress markers.
Conclusion:
Jobelyn significantly reduced oxidative stress and improved hematological indices in school-aged Nigerian children with SCD. Further longitudinal studies and Jobelyn trials in children with SCD are recommended to determine its benefits and safety profile.
Genetic Insights into Myeloid Malignancies: A Comparative Analysis of NCCN Guidelines, the World Health Organization Classification, and the ICC System
Authors: Puentes Roisin , Feld Jonathan , Smith Christopher G. , Lyle Derek D 
Published: December 2024

Background: The 2023/2024 NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for myeloid malignancies, alongside the 5th edition of the World Health Organization (WHO) Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasms, and the 2022 International Consensus Classification of Myeloid Neoplasms and Acute Leukemias (ICC), provide comprehensive frameworks for understanding the genetic landscape of these diseases. This study aims to compare the genetic references in these guidelines to highlight the breadth of genetic markers implicated in myeloid malignancies.
Methods: We systematically reviewed the NCCN guidelines, the WHO, and the ICC system for references to genes relevant to myeloid neoplasms. The myeloid neoplasms assessed included chronic myeloid leukemia (CML), polycythemia vera (PV), essential thrombocythemia (ET), myeloproliferative neoplasms (MPN), myelodysplastic syndromes (MDS), MDS/MPN overlap syndromes, chronic neutrophilic leukemia (CNL), and chronic eosinophilic leukemia (CEL).
Results: A total of 185 unique genes were identified as relevant to myeloid malignancies within the guidelines, 87 of which were fusions. 89 genes were mentioned in the NCCN guidelines, 74 in the WHO classification, and 143 in the ICC. Some genes were uniquely associated with specific disease states, while others were relevant across various myeloid malignancies. An overlap of 76 genes, including 32 fusions was noted across all guidelines.
Conclusion: The findings underscore the critical role of comprehensive genetic testing in the diagnosis and management of myeloid malignancies. The overlap and unique genetic markers identified in the NCCN, WHO, and ICC guidelines emphasize the need for large panel testing across myeloid malignancies to ensure precise genetic characterization of the relevant genes, enabling accurate diagnosis, risk stratification, prognostication, and the tailoring of therapeutic strategies to the patient, including the use of drugs targeted for only certain mutations. The high gene count captured within the treatment guidelines emphasizes the necessity for comprehensive genetic testing to enhance clinical outcomes and advance personalized medicine in the management of myeloid neoplasms.
Hemoglobin A2 Values in Sickle Cell Disease Patients Reveal Alarming Heterozygosity
Authors: Pendharkar Dinesh , Nirmal Garima 
Published: December 2024

Sickle cell disease (SCD) is one of the most common genetic diseases, affecting more than 300000 patients in India. It is characterized by homozygous hemoglobin S or other HbS-associated variants. However, large datasets have not been reported. The prevalence of thalassemia is equally high in the Indian population. High-performance liquid chromatography data are now available. However, heterozygosity has not been well studied. HbA2 values require further consideration.
We conducted a prospective observational study to collect data from large cohorts and analyze HbA2 % in relation to hematological parameters in one geographical tribal district. A total of 691 patients, including 575 homozygous (HbSS) and 116 patients with HbS &gt; 50% and HbA2 values ≥ 4%, were reviewed. High-performance liquid chromatography charts were used to differentiate the Hb variants.
The median age of SCD was was16 (interquartile range {IQR] 9-25) years, and 360 (52.1 %)were males. The median A2 was 1.9% (IQR 1.4-2.7) Hb S was 67.9 % (IQR,62.9-72.7), Hb F was 26.2% (IQR 21.5-30.9).There were 116 (16.68 %) patients with HbA2 levels of 4 and above, with a median age of 16.5 (IQR 9-27) years and 59.5 % males. The value of HbA2 % ranged from to 4-8 in 100 patients; one had a value of 37, and remaining between 9-22. This group had median Hb A2 % of median 5.1 (IQR 4.5-6.3) , HbS % of 65.4 (IQR 65.0-70.2) , HbF% of 23.25 (IQR 16.8-29.3)and A0 of 6.6 (IQR 4.4-8.2).The median hematological parameters were Hb 7.8 g/dL (IQR 6.0-9.1), MCV 71.4 fL (IQR 66.8-76.6) , MCH 22.6 pg (IQR 21.1-24.4) , MCHC 31.3 g/dL (IQR 29.9-32.9) Total count 14.4 x103 /µL (IQR 8.6-18.8).A higher HbA2 level was associated with higher MCV (Spearman's rho value 0.008; p =0.01) and positively correlated with MCH (Spearman's rho value=0.003; p =0.01).
In conclusion,the data showed a strikingly high incidence of elevated Hb A2 (16% of the SCD population). Considering the higher-than-normal values of HbA2 in the sickle population in India, it is important to generate even larger data. For better understanding, the molecular classification of patients should be incorporated. Therefore, there is a need to reclassify the levels of HbA2 to qualify for heterozygosity.
Advancing agriculture with functional NM: “pathways to sustainable and smart farming technologies”
Authors: Alam Mir Waqas , Junaid Pir Mohammad , Gulzar Yonis , Abebe Buzuayehu , Awad Mohammed , Quazi S. A. 
Published: December 2024

AbstractThe integration of nanotechnology in agriculture offers a transformative approach to improving crop yields, resource efficiency, and ecological sustainability. This review highlights the application of functional NM, such as nano-formulated agrochemicals, nanosensors, and slow-release fertilizers, which enhance the effectiveness of fertilizers and pesticides while minimizing environmental impacts. By leveraging the unique properties of NM, agricultural practices can achieve better nutrient absorption, reduced chemical runoff, and improved water conservation. Innovations like nano-priming can enhance seed germination and drought resilience, while nanosensors enable precise monitoring of soil and crop health. Despite the promising commercial potential, significant challenges persist regarding the safety, ecological impact, and regulatory frameworks for nanomaterial use. This review emphasizes the need for comprehensive safety assessments and standardized risk evaluation protocols to ensure the responsible implementation of nanotechnology in agriculture.
Does the intervention of the school-based health promotion programme “Join the Healthy Boat” have equal or differential effects on weight status and health-related behaviours in children from a high or low socio-economic background? – A randomised controlled trial
Authors: Kobel Susanne , Wartha Olivia , Steinacker Jürgen M. , Dreyhaupt Jens 
Published: December 2024

Abstract
Background
Worldwide, the prevalence of childhood overweight and obesity increases. Children with low socioeconomic status (SES) are more often affected by overweight and obesity. SES is also associated with health behaviours. In order to avoid health disparities, school-based health promotion programmes such as “Join the Healthy Boat” can help. Intervention outcomes can differ by SES; therefore, the purpose of this study was to investigate whether the intervention had equal or differential effects both on weight status and health-related behaviours in children from high and low SES.

Methods
One thousand six hundred twenty children’s data (7.1 ± 0.6 years; 50.6% male) was analysed; anthropometric data was taken on-site, other health-related parameters, such as physical activity, nutrition, and screen media use, as well as SES were assessed subjectively. Logistic regression models and GEEs were calculated.

Results
Comparisons by SES show that there were significant differences in children’s characteristics and health behaviours such as migration background, height, weight, BMI percentiles, weight status, family education level, household income, physical activity behaviour, screen media use, soft drink intake and breakfast skipping. After one year, there were no intervention effects for overweight status, physical activity, or screen media use, but children with high SES in the intervention group skipped breakfast significantly less often than in the control group (5.34 [1.44;19.85], p = 0.01). Parental education level and household income were also assessed separately, with similar results. Interaction analysis revealed no significant effects apart from an interaction effect for breakfast behaviour (p = 0.02).

Conclusions
The health-promotion programme “Join the Healthy Boat” has the potential to promote children’s health via a school-based intervention and therefore, reach all children independent from their background. This study shows vast gaps between several health behaviours of primary school children depending on their SES, favouring those children coming from more privileged families. A longer implementation may possibly show more effects.

Trial registration
DRKS00000949.