bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical, Pathological and Outcomes of Mixed Phenotypic Acute Leukemia Patientes:10 Years Real - World Peruvian Data
Authors: Chuquillanqui Gabriela S , Alcarraz Cindy Elizabeth , Lopez Chavez Lourdes Isabel , Vasquez Jule F , Quintana Shirley , Mantilla Raul 
Published: December 2024

INTRODUCTION
Mixed-phenotype acute leukemia (MPAL) is a diverse group of blood cancers where the leukemia cells have characteristics of multiple cell lineages and constitute 2-3% of all acute leukemias. MPAL is generally considered to have a poor prognosis.

OBJECTIVE
The present study highlighted the clinical, pathological, and survival outcomes of MPAL cases diagnosed in the National Cancer Center of Peru for 10 years.

METHODS
We conducted a retrospective observational study on 47 cases diagnosed with MPAL between 2012 and 2021. The diagnosis of MPAL was based on the World Health Organization (WHO) 2008 and 2016 classification. We used descriptive statistics to analyze categorical and continuous variables. Overall survival was analyzed by the Kaplan-Meier method and the differences according to characteristics by log-rank test.

RESULTS
There were 29 men and 18 women: with a median age of 35 years [range 21-54]. The median hemoglobin was 7.85 g/dl [7.25 - 9.25 g/dl]. The median total leukocyte count was 38.005 x 109/L [6.425 - 146.58 109/L]. The median platelet count was 45 × 109/L [17.75 - 104.25 109/L]. Immunophenotyping disclosed B + myeloid (n:35,74.5%), T + myeloid (n:7,14.9%), B + T (n:3, 6.4%), or trilineage (n:2,4.2%) combinations. Cytogenetics is performed on 26 patients, evidenced by t(9;22)/(Ph+) (23%), complex (23%), aberrant (7%), or normal (46%) karyotypes. Mutations are performed on 30 patients, BCR/ABL p190 or p210 mutations were performed in 40% of cases, FLT3 ITD in 6.7%, and MLL/AF4 in 3.3%. The most common cytogenetic abnormality in B/myeloid MPAL was translocation t (9;22).
Response to induction treatment was available in 29 patients, 19 received ALL, 10 AML, and ALL treatment induced a response in 42 %, with AML therapy in 50 %. Eighteen (38.3%) patients did not receive any treatment, 42 (89.3%) died, all except two died within the month since diagnosis, 4 (8.5%) underwent allogeneic stem cell transplants, and all of them were alive at the latest follow-up. The overall median survival was 10 months, and the five-year survival estimation was 12%. Leukocytosis &gt; 30 x 109/L at diagnosis and non-complete response after induction therapy were predictors for poor outcomes (P =0.031; P= 0.022).

CONCLUSIONS
MPAL is a rare and high-risk disease. Patients should be considered for transplantation in their first remission. Unfortunately, we have lots of patients who die early without treatment.
Effectiveness of Eculizumab in Patients with Paroxysmal Nocturnal Hemoglobinuria in China: A Real World Study
Authors: LI He , Yu Xinmei , Qiu Juan , Jia Lei , Zhu Huanling , Niu Ting , Liu Zhigang , He Chuan 
Published: December 2024

Objective: To observe the real-world efficacy and safety of eculizumab in the treatment of paroxysmal nocturnal hemoglobinuria (PNH) in China.
Methods: The baseline, symptoms, laboratory tests, and adverse reactions before and after treatment of PNH patients treated with eculizumab in the West China Blood Alliance from January 2024 to the present were collected.
Results: A total of 12 PNH patients were included, consisting of 5 males and 7 females, with a median age of 37 years. Three patients had concomitant aplastic anemia, 7 require blood transfusion, 2 had a history of thromboembolic disease, and 4 had chronic renal insufficiency. None of the 11 patients who were screened with C5 R885 mutation was positive. The proportion of patients with monthly income of less than 5000 yuan was 72.7%. The median Hb was 53.5 g/L, the median reticulocyte count was 12.21%, and the LDH level was 2146 IU/L before treatment. The median percentage of CD55- and CD59-negative neutrophils were 96.8% and 93.8%, respectively. And the percentages of CD55- and CD59-negative red cells were 42.4% and 43.5%, respectively, the median percentage of FLARE-negative granulates was 95.3%, and the median percentage of FLARE-negative monocytes was 91.2%. There were no patients with C5 R885H gene mutation. The median duration of treatment was 14 weeks. After 4 weeks of treatment, the median Hb was 71 g/L, the count of reticulocyte was 7.61%, and the LDH level was 504 IU/L; after 8 weeks of treatment, the median Hb was 80.5 g/L, the reticulocyte count was 9.55%, and the LDH level was 275 IU/L. Five patients became transfusion-independent after 8 weeks, and the frequency of blood transfusion was reduced in 2 patients. Cr levels decreased in 2 patients. The proportion of patients with mildly elevated bilirubin after the last follow-up compared to the lowest value was 85.7%. After treatment, 83.3% of patients with positive Coombs C3 were found. During the treatment, there was one case of respiratory infection and two cases of headache as mild adverse events. One case with suspected intracranial infection was reported as a serious adverse event. No new thrombotic events occurred.
Conclusion: Eculizumab has good control over anemia and hemolysis-related symptoms in PNH patients, and its safety is good. After being included in the medical insurance system, it is applicable to PNH patients in China.
Improved Outcomes with Venetoclax in Combination with Mitoxantrone Liposome and Cytarabine for Myeloid Sarcoma By Preliminary Observations
Authors: Tong Hongyan , Luo Yingwan , Huang Liping , Zhou Xinping , Mei Chen 
Published: December 2024

Introduction: Myeloid sarcoma (MS) is a rare malignant myeloid tumor of the blood system that can affect any part of the body and often occurs in conjunction with acute myeloid leukemia. In the 2022 WHO classification, myeloid sarcoma is recognized as an independent entity, with a significant heterogeneity in overall prognosis and a short survival time. Currently, there is no consensus on induction regimen. Previous studies indicate that intensified cytarabine therapy or Venetoclax with hypomethylation agents has yielded not ideal responses. Using venetoclax combined with intensive therapy might synergistically enhance the anti-sarcoma effect. Considering that liposomal mitoxantrone has strong penetrability to extramedullary sites; therefore, we designed the triple regimen of Venetoclax, Mitoxantrone Liposome and Cytarabine (VMA) for the newly diagnosed myeloid sarcoma patients at the First Affiliated Hospital of Zhejiang University, aiming to evaluate the efficacy and safety.
Methods: Patients received the following VMA regimen: Venetoclax 100mg on day 1, 200mg on day 2, and 400mg on days 3 to 7; Mitoxantrone Liposome 30mg on day 1; Cytarabine 100mg/m2 on days 1-7. Each treatment cycle lasted for 28 days. Patients who achieved CR, CRh, or CRi, as per the center's treatment guidelines, were eligible for transplantation at any time point. The primary objective being to evaluate the proportion of patients achieving complete remission (CR) after two cycles. The evaluation of residual lesions through PET-CT or enhanced CT.
Results: A total of 3 patients were treated with VMA regimen for up to four courses. After 1-2 cycles, the MS mass notably reduced. Currently, 2 out of 3 patients have achieved complete remission after two cycles. A 27-year-old male patient had an anterior-mediastinal involvement (5.1*2.9 cm). After 1 cycle of VMA regimen, the anterior mediastinal mass dramatically decreased to 2.5*0.1 cm. He achieved CR after two cycles of VMA regimen and underwent an Allo-SCT. A 42-year-old male with a 3.9*2.2 cm urinary issue achieved complete remission after four VMA regimen cycles but declined transplantation and is under monitoring. A 44-year-old female had a gastic involvement (1.9*1.2cm). After 1 cycle of VMA regimen, his gastric wall thickening was immeasurable.
The most frequently reported adverse events of Grade 2-3 included anemia, nausea, fatigue, anorexia, and hyponatremia. All adverse events could be managed and improved through dose adjustments and supportive treatment.
Conclusions: The initial observations of VMA regimen have been found to be safe and effective, with encouraging complete response rates in newly diagnosed MS patients. Further correlative trials and analysis are currently underway to thoroughly observe the efficacy and safety of the VMA regimen.
When clinicians and patients disagree on vaccination: what primary care clinicians can learn from COVID-19-vaccine-hesitant patients about communication, trust, and relationships in healthcare
Authors: Purcell Natalie , Usman Hajra , Woodruff Nicole , Mehlman Haley , Tobey-Moore Leah , Petrakis Beth Ann , Oliver Karen Anderson , Kaplan Adam , Pyne Jeffrey M. , Manuel Jennifer K. , DeRonne Beth M. , Bertenthal Dan , Seal Karen H. 
Published: December 2024

Abstract
Background
In the United States, discourse on COVID-19 vaccination has become polarized, and the positions of public health officials are met with skepticism by many vaccine-hesitant Americans. This polarization may impact future vaccination efforts as well as clinician-patient relationships.

Methods
We interviewed 77 vaccine-hesitant patients and 41 clinicians about COVID-19 vaccination communication in primary care as part of a Veterans Affairs (VA) trial evaluating a vaccine-communication intervention. This paper reports the findings of a qualitative analysis focused on one aspect of those interviews—the disconnect between primary care clinicians’ and patients’ perceptions about COVID-19 vaccination communication and decision-making.

Results
Rapid qualitative analysis of semi-structured interviews revealed fundamental differences in how clinicians and patients understood and described the reasoning, values, and concerns underlying COVID-19 vaccine hesitancy. These differences were significant and value-laden; they included negative judgments that could undermine communication between clinicians and patients and, over time, erode trust and empathy.

Conclusion
We advocate for empathic listening and suggest communication strategies to bridge the divide between clinicians and vaccine-hesitant patients.
A systematic review and meta-analysis of evidence-based practice and its associated factors among health professionals in Ethiopia
Authors: Gudeta Tolesa Gemeda , Terefe Ayana Benti , Mengistu Girma Teferi , Sori Seboka Abebe 
Published: November 2024

Abstract
Background
Evidence-based practice (EBP) entails utilizing the most up-to-date information to inform clinical decisions. Healthcare professionals at all levels are encouraged to integrate the latest research evidence to ensure high-quality care. In Ethiopia, there is a lack of comprehensive, nationally representative data on the prevalence of EBP among healthcare workers. This systematic review and meta-analysis aims to assess the overall prevalence of EBP and its associated factors among health professionals in Ethiopia.

Methods
This systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The investigators searched electronic databases, including PubMed, Embase, Web of Science, Scopus, Cochrane Library, and Google Scholar, for studies published up to June 1, 2023. Two reviewers independently carried out the extraction of data and evaluation of study quality. We employed STATA version 14 for data synthesis and statistical analysis. The investigators used random-effects and fixed-effects models to calculate pooled odds ratios (ORs) and 95% confidence intervals (CIs) to determine the correlation between dependent and independent factors. The researchers conducted subgroup analysis to explore heterogeneity among the studies included and checked heterogeneity using the I2 statistic. The reviewers assessed publication bias using funnel plots and Egger’s regression test.

Results
The initial search yielded 215 articles, of which 21 met the inclusion criteria. The pooled prevalence of good evidence-based practice among health professionals in Ethiopia was found to be 47.64 [95% CI: 41.33 to 53.96]. Having a masters and above educational status [pooled odds ratio (OR = 3.11; 95%CI: 1.945 to 4.95], good knowledge of EBP [OR: 2.44; 95%CI: 2.14, 2.78], training in EBP [OR = 2.30; 95% CI: 1.91, 2.77], availability of EBP guidelines [OR: 2.05; 95%CI: 1.60, 2.61], internet access [OR: 1.79; 95%CI:1.47, 2.18], availability of free time [OR: 2.05; 95%CI: 1.54, 2.72], presence of administrative support [OR: 1.89; 95%CI: 1.34, 2.67], clinical experience > 5 years [OR: 2.26; 95%CI: 1.54, 3.33], and positive attitude towards EBP [OR: 1.87; 95%CI: 1.53, 2.28] were significantly associated good evidence-based practice in Ethiopia.

Conclusions
Despite the importance of EBP in improving healthcare outcomes, its implementation among healthcare professionals in Ethiopia remains suboptimal. This study also identified modifiable factors associated with EBP adoption. Meanwhile, most of these factors are related to individuals and organizations. Strategies aimed at enhancing access to training and resources and fostering a supportive organizational culture are crucial for promoting EBP uptake and ultimately improving healthcare quality in Ethiopia.
Prescribing patterns before the initiation of novel antidiabetic medicines in public, occupational, and private healthcare: a register study reflecting the guidelines of care in type 2 diabetes
Authors: Rättö Hanna , Nurminen Mikko , Aaltonen Katri 
Published: December 2024

Abstract
Background
Disparities in access to healthcare has been implied before in Finland, a country with universal healthcare but de facto tiered primary care. Less is however known about the content of care provided in different settings. Previous studies indicate potential disparities in prescribing newer medicines between healthcare sectors. We compared the preceding prescribing patterns of patients who initiated a sodium-glucose co-transporter 2 (SGLT2) inhibitor or a glucagon-like peptide-1 (GLP-1) analogue in public, occupational, and private healthcare.

Methods
We used logistic models and patient-level register data from the city of Oulu, Finland, during 2014–2018. Among patients who initiated SGLT2 inhibitors or GLP-1 analogues, we studied whether it was a first-line treatment or if other antidiabetic medicines preceded the use. In addition, prior use of statins (a lipid-lowering medicine) and insulins were studied. Clinical guidelines for type 2 diabetes recommend in most cases metformin in first-line, and insulin only at later stages or in case of severe hyperglycaemia. Using a lipid-lowering medicine is typically recommended for all.

Results
The examined novel antidiabetic medicines were seldom initiated in first-line, and no significant differences were observed for preceding statin use across sectors, net of patient characteristics. However, patients in the public sector were more likely to have used insulin previously compared to patients in occupational sector.

Conclusions
Before the initiation of the examined novel antidiabetic medicines, no marked differences across sectors in the use of other antidiabetic medicines or statins were observed. The higher likelihood of prior insulin use in the public sector might reflect initiation at a later stage and/or unobserved differences in clinical characteristics across patient populations.
Metastasizing dysgerminoma in an inland bearded dragon (Pogona vitticeps)
Authors: Schmidt-Ukaj Silvana , Brunthaler Rene , Gumpenberger Michaela 
Published: December 2024

Abstract
Background
Malignant dysgerminomas are infrequently reported ovarian neoplasms in animals, especially in exotic pets (non-traditional companion animals [NTCAs]). In the few published case reports on reptilian species, examples are primarily postmortem without antemortem (clinical) assessment.

Patient presentation
An adult, 13-year-old, spayed female inland bearded dragon (Pogona vitticeps) presented with lethargy, a right-sided head tilt, unilateral exophthalmos and ventrotemporal strabismus on the right eye. On examination, a palpable mass (approximately 3.5 cm in diameter) was detected within the mid coelomic cavity. Computed tomography revealed a retrobulbar swelling and lytic bone lesions affecting the right frontal bone and several vertebrae (T11, T13, and T14). Multiple nodules of soft tissue opacity were also detected within the lungs, liver, and coelomic fat bodies. Haematology revealed leukocytosis with heterophilia and toxic granulation of heterophils. On the basis of these results, differential diagnoses included disseminated abscesses, granulomas (e.g., due to mycobacteriosis) and neoplasms. The lizard was subsequently euthanized due to end-stage disease and a poor prognosis. Postmortem gross examination and histopathology revealed a primary ovarian dysgerminoma with evidence of widespread metastasis as well as localized tissue destruction affecting the right retrobulbar space and frontal bone, the spinal column, the lungs, the liver, and both coelomic fat bodies.

Conclusions
This report describes a case of malignant dysgerminoma with widespread intraosseous and visceral metastases in a captive inland bearded dragon (Pogona vitticeps).
ASGR1 deficiency improves atherosclerosis but alters liver metabolism in ApoE-/- mice
Authors: Svecla Monika , Moregola Annalisa , Dalt Lorenzo Da , Nour Jasmine , Baragetti Andrea , Uboldi Patrizia , Idini Alessandra , Wuhrer Manfred , Beretta Giangiacomo , Falck David , Bonacina Fabrizia , Norata Giuseppe Danilo 
Published: November 2024

Abstract
Abstract
The asialoglycoprotein receptor 1 (ASGR1), a multivalent carbohydrate-binding receptor that primarily is responsible for recognizing and eliminating circulating glycoproteins with exposed galactose (Gal) or N-acetylgalactosamine (GalNAc) as terminal glycan residues, has been implicated in modulating the lipid metabolism and reducing cardiovascular disease burden. In this study, we investigated the impact of ASGR1 deficiency (ASGR1−/−) on atherosclerosis by evaluating its effects on plaque formation, lipid metabolism, circulating immunoinflammatory response, and circulating N-glycome under the hypercholesterolemic condition in ApoE-deficient mice. After 16 weeks of a western-type diet, ApoE−/−/ASGR1−/− mice presented lower plasma cholesterol and triglyceride levels compared to ApoE−/−. This was associated with reduced atherosclerotic plaque area and necrotic core formation. Interestingly, ApoE−/−/ASGR1−/− mice showed increased levels of circulating immune cells, increased AST/ALT ratio, and no changes in the N-glycome profile and liver morphology. The liver of ApoE−/−/ASGR1−/− mice, however, presented alterations in the metabolism of lipids, xenobiotics, and bile secretion, indicating broader alterations in liver homeostasis beyond lipids. These data suggest that improvements in circulating lipid metabolism and atherosclerosis in ASGR1 deficiency is paralleled by a deterioration of liver injury. These findings point to the need for additional evaluation before considering ASGR1 as a pharmacological target for dyslipidemia and cardiovascular disorders.

Graphical abstract
Intrauterine administration of peripheral blood mononuclear cells helps manage recurrent implantation failure by normalizing dysregulated gene expression including estrogen-responsive genes in mice
Authors: Kitawaki Yoshimi , Horie Akihito , Ikeda Asami , Shitanaka Shimpei , Yanai Akihiro , Ohara Tsutomu , Nakakita Baku , Sagae Yusuke , Okunomiya Asuka , Tani Hirohiko , Mandai Masaki 
Published: December 2024

Abstract
Background
Intrauterine peripheral blood mononuclear cell (PBMC) therapy for recurrent implantation failure (RIF) has been reported to improve embryo implantation by acting on the endometrium. However, the exact mode of action of PBMC on the endometrium of patients with RIF remains unclear. In addition, the differences in the therapeutic effects of PBMC therapy with and without human chorionic gonadotropin (hCG) are unknown. Therefore, in this study, we investigated the changes in the endometrium during the implantation phase induced by PBMC administration and the differences in the efficacy of this therapy with and without hCG using a mouse model of implantation failure (IF).

Methods
IF model was established by the subcutaneous administration of low-dose RU486. Pregnant mice were randomly divided into five groups: control, IF, culture medium, PBMC, and PBMC-hCG (the latter three groups were IF model mice with intrauterine administration). The pregnancy rate and the number and size of implantation sites were recorded during early pregnancy (day 7.5). Uteri from the preimplantation phase (evening of day 3.5) were collected and analyzed using RNA-sequencing (RNA-seq).

Results
The pregnancy rate, the number of implantation sites, and the number of normal-sized implantation sites were significantly decreased in the IF model and were improved in the medium, PBMC, and PBMC-hCG groups. RNA-seq data showed that PBMC treatment normalized the expression of the majority of dysregulated genes in the endometrium during the preimplantation phase in the IF model, especially the overexpression of estrogen-activated genes. In addition, PBMC treatment increased the expression of local glucocorticoid receptors and suppressed the expression of inflammation-related genes, whereas no significant changes in blood estradiol and glucocorticoid levels were observed. These changes were more pronounced in the PBMC-hCG group and were consistent with the pregnancy outcomes.

Conclusions
Intrauterine administration of PBMC before embryo implantation promoted embryo implantation in the IF mouse model, and hCG enhanced pregnancy outcomes. PBMC modulated steroid receptor expression and suppressed inflammation and excessive estrogen action.
Sex-dependent effects of chronic jet lag on circadian rhythm and metabolism in mice
Authors: Ma Tiantian , Matsuo Ryohei , Kurogi Kaito , Miyamoto Shunsuke , Morita Tatsumi , Shinozuka Marina , Taniguchi Fuka , Ikegami Keisuke , Yasuo Shinobu 
Published: December 2024

Abstract
Background
The circadian clock integrates external environmental changes into the internal physiology of organisms. Perturbed circadian clocks due to misaligned light cycles increase the risk of diseases, including metabolic disorders. However, the effects of sex differences in this context remain unclear.

Methods
Circadian misalignment was induced by a chronic jet lag (CJL) shift schedule (light-on time advanced by 6 h every 2 days) in C57BL/6N male and female mice. Core body temperature and activity rhythms were recorded using a nano tag, and the gene expression rhythms of clock and clock-controlled genes in the liver and adrenal glands were analyzed using qPCR. Glucose metabolism and insulin response were evaluated using glucose tolerance, insulin sensitivity, and glucose response assays. Castration and testosterone replacement were performed to assess the fundamental role of testosterone in male phenotypes under CJL.

Results
Under CJL treatment, male mice exhibited increased weight gain, whereas females exhibited decreased weight gain compared to that of the respective controls. CJL treatment induced a lower robustness of circadian rhythms in core body temperature and a weaker rhythm of clock gene expression in the liver and adrenal glands in females, but not in males. Only male mice exhibited glucose intolerance under CJL conditions, without the development of insulin resistance. Castrated mice without testosterone exhibited decreased weight gain and reduced robustness of body temperature rhythm, as observed in intact females. Testosterone replacement in castrated mice recovered the CJL-induced weight gain, robustness of temperature rhythm, and glucose intolerance observed in intact males.

Conclusions
Significant sex-based differences were observed in circadian clock organization and metabolism under CJL. Testosterone plays a crucial role in maintaining the circadian clock and regulating CJL metabolism in males.