bluuebunny/crossref_metadata_2025 huggingface dataset:
Antibody Drug Conjugates with a Novel Translation Inhibitor Payload Demonstrate Cytotoxicity and Tumor Growth Reduction in Multiple Myeloma Models
Authors: Chapman-Arvedson Tara L.
Published: December 2024

Background

Antibody drug conjugates (ADCs) are a validated modality for the targeted delivery of cytotoxic payloads to myeloma cells while sparing healthy tissue. To achieve the full potential of ADCs in multiple myeloma patients, it will be important to have ADCs that incorporate payloads with non-overlapping mechanisms of action (MOA) as compared to existing therapies. By mining a proprietary collection of small molecule natural products (NPs), Hexagon Bio has identified a novel protein translation inhibitor, HB-06510, which exhibits favorable physicochemical properties and significant sensitivity in myeloma cell lines. HB-06510 has been conjugated to antibodies that bind myeloma antigens and has been shown to induce myeloma cell cytotoxicity in vitro and in vivo.

Methods and Results

Hexagon Bio has established a platform to identify new NPs and determine their MOA. This platform uses a proprietary algorithm integrated with machine learning, genetic screening, and synthetic biology to identify, produce, and define the MOAs of new NPs, primarily isolated from our fungal library comprising > 100,000 strains. Using this platform, we identified a NP that was potently cytotoxic across a panel of cancer cell lines, including multiple myeloma (≤ 3.2 nM average EC50 and 100% killing across 10 cell lines in a 72 hour assay). To determine the mechanism of action, we used genetic screening and found that this NP inhibited protein translation. Physicochemical evaluation of the NP revealed it had good properties for a potential ADC payload (good solubility, low lipophilicity, good stability in human plasma and lysosomal preparations, no reactivity with glutathione), it has a site for linker attachment and is amenable to semi-synthesis and medicinal chemistry. Further cytotoxicity profiling demonstrated that HB-06510 is cytotoxic to multi-drug resistant cells, including those expressing high levels of efflux pumps such as Pgp and ABCG2, indicating that HB-06510 is not a substrate for these pumps. We also demonstrated that HB-06510 is cytotoxic to both fast- and slow-cycling cells and induces immunogenic cell death.

To evaluate the potential for HB-06510 to be an ADC payload, we conjugated HB-06510 to antibodies that bind myeloma antigens BCMA, CS1 and CD38 and have demonstrated anti-myeloma cell cytotoxicity in vitro and in vivo. These results will be presented.

Conclusions

We have identified a novel protein translation inhibitor payload that is highly potent, has good drug-like properties and shows effective anti-myeloma cell activity in vitro and in vivo when conjugated to anti-myeloma antibodies. ADCs with this MOA are distinct from both currently-available targeted therapeutics and chemotherapy and have the potential to provide benefit to patients.
Cutting Costs and Enhancing Care: The Financial Burden of Factor VIII Testing in Thrombosis and Stroke Workup
Authors: Singh Anaiya , Gaddam Shiva Jashwanth , Ramadas Poornima
Published: December 2024

Introduction:

Elevated factor VIII is often linked to increased thrombosis risk and has been used as a tool to measure outcomes and prognostication in thrombotic events, but its direct contribution remains uncertain. Current guidelines suggest limited benefit in testing of factor VIII levels in thrombophilia(s) and stroke(s). Despite this, factor VIII testing is frequently performed during routine workup of venous thromboembolic events (VTEs) and cerebrovascular accidents (CVAs). Our study examines the financial impact of unnecessary and clinically irrelevant factor VIII testing in these scenarios.

Methods:

At our institution, we performed a retrospective study approved by the Institutional Review Board (IRB), analyzing data from 462 patients who underwent factor VIII level testing from December 2019 to December 2022. We excluded patients whose tests were performed for reasons other than evaluating thrombophilia or cerebrovascular accidents (CVAs) and analyzed data for 157 patients. Our data collection encompassed patient demographics, indications for testing, and insurance coverage. This information was used to assess the financial impact on our institution related to the unnecessary testing of factor VIII levels in patients with an increased risk of thrombosis and stroke.

Results:

The median age of testing for factor VIII levels was 34+/-7 years, with females (96) constituting 61.1% and males contributing (50) 38.9%. Factor VIII levels were tested for 61 patients with Transient Ischemic Attacks (TIAs) and CVAs and in 96 patients with VTEs. Out of all the 157 patients tested, 27 were covered by Medicare, 71 by Medicaid and 59 benefitted from private-based insurance. In-house testing for this gene costed approximately $180 per test in 2019, with the cost inflation up to $260 after 2020.

Conclusions:

Over a three-year period, our analysis revealed an expenditure of approximately $30,000 USD on factor VIII level testing as part of the diagnostic workup for thrombophilia and stroke, despite insufficient clinical evidence supporting its necessity. This study aims to disseminate these findings within our institution to minimize clinically unwarranted testing, enhance patient outcomes, and optimize the cost-benefit ratio by educating clinicians. By addressing this, we hope to reduce the financial burden on healthcare systems while adhering to clinical guidelines.
Using Drug-Induced RNA Sequencing and David Analysis to Identify Targeted Therapies for Use in Combination with Duocarmycin SA for the Treatment of Acute Myeloid Leukemia
Authors: Chen William A , Filippov Valeri , Fang Jie , Ochoa Pedro , Casiano Carlos A , Jin Hongjian , Dovat Sinisa , Yang Jun J. , Boyle Kristopher E , Francis Olivia
Published: December 2024

Acute myeloid leukemia (AML) is a hematological malignancy that is associated with uncontrolled clonal expansion and the accumulation of myeloid blasts in the bone marrow. A major challenge of the treatment of AML is the high relapse rates that are often observed in patients despite advances in treatment options. Consequently, there remains a need to identify potential therapeutic candidates that can improve patient survival outcomes and reduce the risk of relapse in AML patients. The objective of this study was to utilize RNA sequencing and bioinformatic analyses to identify candidate targeted therapies for use in combination with Duocarmycin SA (DSA), a natural product antitumor antibiotic, for the treatment of AML. We hypothesized that RNA sequencing of DSA treated cells will identify novel genes that can be potentially targeted for AML drug combination studies. To test our hypothesis, human AML cell lines (Molm-14 and HL-60) were treated with high and low concentrations of DSA for 36 hours. Molm-14 cells were cultured with 100 pM (high) and 11.12 pM (low) of DSA and HL-60 cells were cultured with 500 pM (high) and 112.7 pM (low) of DSA. At 36 hours, the cells were harvested, RNA was isolated from the cells using Qiagen's RNeasy mini kit and RNA sequencing and gene expression profiling analysis were performed by the Hartwell Center for Biotechnology and the Center for Applied Bioinformatics at St. Jude Children's Research Hospital, respectively. Functional enrichment analysis was performed using the NIH's Database for Annotation, Visualization and Integrated Discovery (DAVID) tool to identify top DSA-induced pathways that were activated and target genes within the pathways for which targeted drug candidates can be identified. Overlapping differentially expressed genes (DEGs) for all four DSA treated conditions (p-value <0.05, Log >0.5) were visualized using Venny 2.1.0. Our results showed that the top pathway, oxidative phosphorylation, that is activated in all DSA treatment groups is related to mitochondrial induced cell-death. Genes that are involved include mitochondrially encoded cytochrome c oxidase 1, 2 and 3 (MT-CO1, MT-CO2, and MT-CO3). In conclusion, our findings suggest that DSA induced apoptosis in human AML cells is mediated by a mitochondrial mediated mechanisms. Additionally, the list of genes involved in the DAVID analysis provide novel therapeutic targets for which targeted drug candidates can be identified and evaluated in combination with DSA for the treatment of AML.
B12 Deficiency: It's Not Always about Nerves!
Authors: Gibson Spencer , Thomas Melissa , Wang Angelina , Moss Arianna S , Quy Ray , Zhao Eva , Debeusscher Ben P , Pakbaz Zahra
Published: December 2024

Background:

Vitamin B12 deficiency can have numerous health consequences including neurological dysfunction, immune dysfunction, and decreased cognitive function [1,2]. It is lesser recognized that B12 deficiency can result in anemia as well as other cytopenias often seen on CBCs collected during visits with first-contact physicians. This leads to delayed or missed diagnosis of B12 deficiency. The primary objective of the current study is to assess physician knowledge gaps in diagnosing B12 deficiency and adequate workup for cytopenias before referring to a hematologist.

Methods:

This study is a retrospective chart review of 862 adults (Mean age 52.9 ± 18.4, 497 female) seen in a single-provider non cancer hematology clinic at an academic center between February 2020 and July 2023. Data collection included patient demographics, referral reason or diagnosis, referring provider specialty type, and the diagnosis made by the consulting adult classical hematologist in this clinic. Patients lost to follow-up after initial referral have been excluded from this data analysis. B12 deficiency was defined as B12 <400 pg/ml.

Results:

Out of 862 analyzed referrals to this clinic, only 3 included vitamin B12 deficiency within the reason for referral. Of the 360 patients who were referred for various cytopenias (Anemia 43%, Thrombocytopenia 23%, Neutropenia 21%, Bicytopenia 6.5%, Pancytopenia 6.5%), 24% were diagnosed with B12 deficiency by this classical hematologist. Of note, 14% of these B12 deficient patients were referred from Hematology/Oncology providers. Further workup by this classical hematologist showed that 17% of cytopenia cases only had B12 deficiency, while the cause of cytopenia in the remaining was found to be multifactorial and they were found to have other vitamin/mineral deficiency, autoimmune conditions, or viral infection in addition to B12 deficiency. None of the B12 deficient patients presented to this clinic with neurological signs or symptoms.

Conclusion:

Data presented here demonstrates that diagnosing B12 deficiency and adequate work up for cytopenias are a challenge both in primary care and specialty clinics, including Hematology/Oncology specialists. Educational interventions are necessary to improve healthcare providers' skills for timely diagnosis of B12 deficiency and etiology of cytopenias before referring to a hematologist. Last but not least, adding a classical hematologist to the care team for patients with non-cancer blood disorders improves patient outcomes.

Citations:

1. Kumar N. Neurologic aspects of cobalamin (B12) deficiency. Handb Clin Neurol. 2014;120:915-26. doi: 10.1016/B978-0-7020-4087-0.00060-7. PMID: 24365360.

2. Green R, Miller JW. Vitamin B12 deficiency. Vitam Horm. 2022;119:405-439. doi: 10.1016/bs.vh.2022.02.003. Epub 2022 Mar 11. PMID: 35337628.
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 > 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.
Demystifying Genomic and Transcriptomic Landscape of Acute Myeloid Leukaemia-Normal Karyotype Using Deep Sequencing Technology
Authors: Ambayya Angeli , Razali Rozaimi , Roshan Tariq Mahmood , Mansoor Adnan , Sulong Sarina , Hassan Rosline
Published: December 2024

Acute myeloid leukaemia-normal karyotype (AML-NK) comprises almost half of the AML subtypes and exhibits clinical heterogeneity in treatment response and outcome. Hitherto, the genomic landscapes of AML-NK that contribute to the clinical outcome remain veiled. Therefore, this study elucidated the genomic profiles and regulatory networks of AML-NK patients predisposed to their heterogeneous clinical outcome. In this study, 51 AML-NK samples at diagnosis (DX) and 14 paired first complete remission (CR1) were recruited for transcriptome sequencing and eight paired DX and CR1 DNA were selected for targeted DNA sequencing. The targeted DNA sequencing using the Archer HGC VariantPlex Myeloid panel that included 75 myeloid-related hotspots genes led to the ascertainment of mutations for risk stratifications, and suitable biomarkers for minimal residual disease monitoring were put forward in this analysis. The transcriptome sequencing yielded discoveries of DEG profiles and functionally enriched pathways in several subgroup analyses that included the comparison of AML-NK patients with the healthy normal groups, paired DX and CR1, FLT3/NPM1 genotypes, and overall survival (OS) of below and above five years. The DEGs between the DX and CR1 suggested their potentiality for MRD monitoring, especially in AML-NK patients who lacked genomic aberrations. The highlights of the DEG findings are the development of a prognostic scoring model based on the findings of the OS below and above five-year comparison. Six significantly upregulated genes in the (FHL1, SOCS2, IL17RC, STAT4, INHBA and TNFSF8) in the JAK-STAT signalling pathway and cytokine-cytokine receptor interaction were included in the prognostic scoring model that revealed that the gene scores were an independent prognostic marker in the AML-NK patients in this cohort. Next, fusion gene analysis disclosed several novel recurrent fusion genes, including LATS2-SAP18 and HOXA3-HOXA9 that exhibited prognostic relevance in patients with OS below five years. Clinically relevant somatic variants were discovered, including five known single nucleotide variants (SNVs) with targeted therapies. Prognostically significant frameshift insertion-deletions (InDels) were detected in the NPM1, DNMT3A and FLT3 genes. Based on established guidelines, this study incorporated the AML-NK patients' genomic findings and risk stratification. Ultimately, the findings were depicted in an oncoprint that reflected how the genomic discoveries in this study improvised the patient's risk stratification for outcome predictions and potential targeted therapies. Hence, this multifaceted study has provided new insights into the genomic profiles of AML-NK patients and shed light on their heterogeneous clinical outcomes.
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

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

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

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

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

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

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

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.
Accuracy of smartphone hearing tests: a comparative study with traditional pure tone audiometry
Authors: Anka Manir Hamza , Danjuma Salisu Abubakar , Abdulrazak Ajiya , Ghazali Hasheem Muhammed , Nurudeen Adebola Shofoluwe , Yunusa Shuaibu Iliyasu , Adamu Auwal
Published: December 2024

Background

Hearing impairment, a widespread sensory deficit, disproportionately affects low- and middle-income countries. Various hearing assessment methods exist, each with limitations. Pure tone audiometry (PTA), the gold standard, is subjective, unsuitable for children, expensive, and requires expertise. Smartphone hearing tests are emerging as cost-effective, user-friendly alternatives, but they cannot measure bone conduction and occasionally yield false thresholds.

Aim

This study aims to compare smartphone-based hearing tests with PTA in patients at the Aminu Kano Teaching Hospital’s ENT Clinic.

Methods

A cross-sectional descriptive study enrolled participants aged 18 and above, including those with normal hearing and varying degrees of hearing loss. Each participant underwent a smartphone hearing test, screening PTA, and diagnostic PTA. The results were analyzed using SPSS version 22.

Results

The study included 92 subjects (184 ears) aged 18–68 years. Smartphone tests accurately detected 94.3% of ears with normal hearing and 97.5% of ears with hearing loss based on screening PTA. At higher frequencies, the smartphone detected 98.4% of ears with hearing loss, showing a strong positive correlation with PTAv results. At speech frequencies, the smartphone detected 100% of ears with hearing loss, again showing a positive correlation. At lower frequencies, the smartphone detected 73% of ears with hearing loss, showing a positive correlation but with a significant statistical difference.

Conclusion

The smartphone hearing test exhibited a strong positive correlation with screening PTAv in hearing assessment, without a statistically significant difference. This suggests that smartphone hearing tests could serve as a viable alternative for hearing assessments, particularly in low-resource settings. This research has implications for improving access to hearing healthcare in resource-constrained regions.
Longitudinal changes in cardiac mIBG scintigraphy in mild cognitive impairment with Lewy bodies
Authors: Greenfinch Gemma , Hamilton Calum A. , Donaghy Paul C. , Firbank Michael , Barnett Nicola A. , Allan Louise , Petrides George S. , Taylor John-Paul , O'Brien John T. , Thomas Alan J.
Published: December 2024

The aim of this study was to determine whether there was a significant change in cardiac [123I]-metaiodobenzylguanidine uptake between baseline and follow-up in individuals with mild cognitive impairment with Lewy bodies (MCI-LB) who had normal baseline scans. Eight participants with a diagnosis of probable MCI-LB and a normal baseline scan consented to a follow-up scan between 2 and 4 years after baseline. All eight repeat scans remained normal; however, in three cases uptake decreased by more than 10%. The mean change in uptake between baseline and repeat was −5.2% (range: −23.8% to +7.0%). The interpolated mean annual change in uptake was −1.6%.
The Promise and Peril of Entrepreneurship: Job Creation and Survival among US Startups
Authors: Bernstein Shai
Published: December 2024

Shai Bernstein of Harvard Business School reviews “The Promise and Peril of Entrepreneurship: Job Creation and Survival among US Startups” by Robert W. Fairlie, Zachary Kroff, Javier Miranda, and Nikolas Zolas. The Econlit abstract of this book begins: “Explores entrepreneurial job creation, survival, and ownership demographics, detailing a new dataset that follows the universe of startups in the United States, the novel and important findings that resulted from analyzing these and related data, and the implications for evaluating policy and the fundamental nature of entrepreneurship.”
Border Economies: Cities Bridging the U.S.—Mexico Divide
Authors: Zavodny Madeline
Published: December 2024

Madeline Zavodny of University of North Florida reviews “Border Economies: Cities Bridging the U.S. – Mexico Divide” by James Gerber. The Econlit abstract of this book begins: “Explores urban economies on the US–Mexico border, illustrating the ways that these economies interact and shape each other's development.”
Modeling Social Behavior: Mathematical and Agent-Based Models of Social Dynamics and Cultural Evolution
Authors: Bisin Alberto
Published: December 2024

Alberto Bisin of New York University reviews “Modeling Social Behavior: Mathematical and Agent-Based Models of Social Dynamics and Cultural Evolution” by Paul E. Smaldino. The Econlit abstract of this book begins: “Explores ways of thinking about and studying complex social systems using mathematical and computational models, focusing on relatively simple dynamic models to aid in the study of social organisms and what they do together.”
Can AI-assisted therapy (PARO robot) be a treatment option for children hospitalised in an acute mental health ward?
Authors: Kałwa Agnieszka , Popek Lidia , Żurowska Natasza , Opidowicz Monika , Malinowska Katarzyna , Jabłońska Agata , Wojtasik Jakub , Borkowska Alina
Published: December 2024

Cel pracy

Celem badania była ocena zmian, jakie zachodzą w sferze behawioralnej i emocjonalnej u dzieci hospitalizowanych psychiatrycznie z powodu zagrożenia życia i zdrowia, z poważnymi tendencjami autoagresywnymi, po terapii z zastosowaniem interakcji z terapeutycznym robotem PARO.

Metoda

Badanie ma charakter pilotażowy i obserwacyjny. Zostało przeprowadzone w trakcie trzech tygodni. Objęto nim pacjentów przyjętych do szpitala psychiatrycznego z powodu zagrożenia życia i zdrowia, których w drodze randomizacji podzielono na grupę eksperymentalną (pracującą z robotem PARO) i kontrolną (pracującą z pluszową zabawką). Zastosowane metody były związane zarówno z obserwacją zewnętrzną jak i samo opisem dzieci.

Wyniki

Wyniki sugerują, że interakcja z robotem PARO może wpływać zarówno na wzrost pozytywnych, jak i zmniejszenie negatywnych emocji. Jest to związane również ze zwiększeniem liczby interakcji pomiędzy dziećmi.

Wnioski

Rezultaty badania zachęcają do dalszych działań w obszarze wprowadzania sztucznej inteligencji jako potencjału możliwości terapeutycznych, z którego mogą korzystać dzieci z zaburzeniami psychicznymi hospitalizowane z powodu zagrożenia życia i zdrowia.
How to reduce the risk of ischemic stroke? Overview of recommendations and their effectiveness
Authors: Bondos Borys , Niewiadomska Jagoda , Stępień Aleksandra , Paluch Alicja , Skrzypek Jakub , Niekra Aleksandra , Fussek Łukasz , Kochan Robert , Wieczorek Ewelina , Lee Kacper
Published: December 2024

Stroke is a very serious life-threatening condition. It is the second cause of death worldwide [5], while even in non-fatal cases it can result in severe disability and complications [5, 8].
Of all cases, ischaemic stroke is the most common, accounting for 87% of all ischaemic stroke cases [4].
Some hope is offered by the fact that modifiable risk factors are responsible for 90% of ischaemic stroke cases [7, 14]. Consequently, a number of recommendations have been made regarding health-promoting behaviours and treatment goals for diseases associated with an increased risk of stroke in high-risk populations.
The aim of this work is to present risk groups, i.e. patient groups at higher than population risk of stroke, and to assess the effectiveness of the recommendations and the impact of their application on stroke risk.
Methods and materials
We reviewed the literature available on PubMed and Google Scholar using the words: Stroke, ischemic stroke, prevention, epidemiology
Summary
The data analysed clearly indicate that modifiable risk factors are responsible for the majority of cases (up to 90%) of stroke. Identifying risk groups on the basis of the Life's Essential 8 proposed by the American Heart Association for the prevention of cardiovascular disease, yields measurable results in lowering the risk of stroke among patients. Clearly defined standards can also set therapeutic targets for the treatment of conditions and diseases strongly associated with stroke risk and further improve population health.
Primary care plays a very important role, as it is often the patient's first contact with the health care system.
Keywords: Stroke, ischemic stroke, prevention, epidemiology