bluuebunny/crossref_metadata_2025 huggingface dataset:
COVID-19 and Age Disparity in Credit Card Expenditures in Korea: Implications on the Government Relief Fund
Authors: Park Byungjin , Cho Joonmo
Published: December 2023

This study examined the difference in expenditure behavior by age group through an empirical analysis of changes in card expenditure after the COVID-19 outbreak, using card transaction data in Korea. It also investigated whether changes in card spending reflecting changes in expenditure behavior occur because of the spread of infectious diseases. A panel analysis was employed using data from 2018 to 2020. After the outbreak, total expenditure decreased by 15.6%, with the spending of older, middle-aged, and young adults falling by 18%, 15.8%, and 14.1%, respectively. Spending on eating out declined by 24.3%, while that on eating in increased by 2.2%, a tendency that is more prominent for older adults. These findings suggest that the COVID-19 pandemic affected expenditure behavior, and the change varied by age group. This implies that the consumption-boosting effect of the COVID-19 relief fund may differ by age group with the different marginal propensity to consume.
Lifestyle Changes and COVID-19 Related Perceptions of Turkish Healthcare Workers
Authors: Batu Zehra , Batu Mikail , Yanık Akan , Oğur Hülya , Kavcar Simge , Bolat Serhat
Published: December 2023

This study seeks to investigate and understand the perceptions of and lifestyle changes adopted by healthcare workers (HCWs) in Turkey who were on the front line of the fight against the outbreak of COVID-19. A total of 33 female HCWs with bachelor’s degrees were included in the study. In-depth interview techniques were used. The data analysis was performed with MAXQDA 2020 qualitative data analysis package program. The female HCWs perceived COVID-19 as rapidly contagious, deadly, dangerous, and long-term. Their perception as to the cause of the outbreak was akin to conspiracy thoughts such as bioweapon. In addition, the study determined that social media was the preferred medium for getting news because the news given in the traditional media was not trusted. It was seen that the attitude of participants regarding the preventive measures was in line with the recommendations of international organizations. In terms of lifestyle changes, for example, the dietary habits and physical activity levels of all the HCW participants, changed and online environments were used for communication/socialization. Those HCW participants who smoked, stated that smoking increased the risk and severity of COVID-19, and they declared an increase in the amount of their use. Those HCW participants who consumed alcohol, reported that alcohol consumption increased during the period of the outbreak in order to maintain socialization and relaxation. Those HCW participants who did not smoke or drink alcohol mentioned that they did not intend to start. This study contributes to an understanding of the impact on HCWs of significant health events especially in terms of their perceptions of and their lifestyle changes as a result of such health events.
How Does Regional R&D Investment Agglomeration Affect High-Quality Economic Development? Evidence From China
Authors: Meili Zhang , Baizhou Li
Published: December 2023

In order to reduce the environmental pollution of economic development, countries around the world pursue high-quality economic development model. However, the relationship between R&D investment agglomeration and high-quality economic development has not been thoroughly revealed in existing studies. Taking 30 provincial-level regions in China from 2009 to 2018 as research samples, this paper empirically examines the relationship between regional R&D investment agglomeration and high-quality economic development by using system GMM method and spatial econometric model. Theoretical analysis shows that regional R&D investment agglomeration promotes regional high-quality economic development by increasing regional knowledge capital, improving innovation efficiency, and promoting knowledge spillovers through scale effect, synergy effect, and spillover effect, respectively. The empirical results show that regional R&D investment agglomeration can significantly promote regional high-quality economic development. The degree of regional integrated innovation can positively adjust the promotion effect of regional R&D investment agglomeration on regional high-quality economic development. Regional R&D investment agglomeration can effectively promote the high-quality economic development of surrounding regions.
Day Scholars Food Insecurity Experience Scale-Survey Module (DSFIES-SM): Psychometric Analysis
Authors: Kasujja Ibrahim , Melgar-Quinonez Hugo , Nambooze Joweria
Published: December 2023

Background: School feeding programs’ evaluation requires the measurement of food insecurity, a more objective indicator, within school in low-income countries. The Global Child Nutrition Foundation (GCNF) uses subjective indicators to report school feeding coverage rates across many countries that participate in the global survey of school meal programs all year round. Aim: To test the methodological feasibility of measuring a school food insecurity construct as a direct indicator of the effectiveness and efficiency of school feeding programs. Methods: Two-stage sampling was used during the selection of schools and 128 schoolchildren with a mean ( SD) age of 10.5(1.58) were recruited. Item Response Theory (IRT) and Classical Test Theory (CTT) approaches were utilized during DSFIES-SM development. Psychometric analysis was utilized to assess the psychometric properties of the measure of school food insecurity and to establish the construct-level reliability, convergent and discriminant validity of the DSFIES-SM. Results: DSFIES-SM generated acceptable item-level reliabilities, ranging from .75 to .78. The construct-level reliability of the DSFIES-SM was indicated by Cronbach’s α of .78. Composite reliability was at .77. Fit measures and tests of model fitness for confirmatory factor analysis (CFA) (RMSEA < 0.0001; TLI = 1.06; SRMR = 0.043; CFI = 1.00, p = .85) confirmed that the data fitted the model perfectly. Conclusion: DSFIES-SM consists of twelve questions with dichotomous yes/no responses. DSFIES-SM has good convergent and discriminant validity. Findings suggest that the items compose a statistical scale designed to cover a range of severity of school food insecurity. Future replications to establish other forms of validity across different cultural contexts in low-income countries can be of benefit to the present research.
Factors Influencing Occupational Retention of Nurses in Their 20s and 30s
Authors: Lee Eunmi , Kim Yujeong , Lee Haeyoung
Published: December 2023

This study aimed to identify the factors influencing the occupational retention of nurses in their 20s and 30s in South Korea. This descriptive cross-sectional study was conducted using data from the fifth Korean Working Conditions Survey (KWCS) conducted in 2017. Participants comprised 485 registered nurses in their 20s and 30s. Descriptive analysis and logistic regression analyses were conducted. Nurses’ occupational retention rate was low when working long hours, working quickly, standing for long periods, and if exposed to physical and verbal abuse. Nurses’ occupational retention rate was high when education or interventions in work-related health and safety were provided. To increase occupational retention, optimal work hours should be assigned, working speed should be adjusted, physical and verbal abuse should be prevented, and various forms of health and safety education should be provided. Regulations and intervention programs that improve nurses’ work environments should also be provided.
Burnout Syndrome and Associated Factors Among Health Care Professionals Working in Dessie Comprehensive Specialized Hospital, Dessie, Ethiopia
Authors: Anbesaw Tamrat , Zenebe Yosef , Abebe Melkamu , Tegafaw Teshome
Published: December 2023

Burnout is a mental, emotional, and physical exhaustion that affects many healthcare workers. However, there is a lack of information in Ethiopia. Therefore, this study aimed to assess the prevalence of burnout syndrome and identify the associated risk factors among healthcare professionals in Dessie Comprehensive Specialized Hospital, Ethiopia. A cross-sectional study was conducted on randomly selected 251 health workers at Dessie Comprehensive Specialized Hospital. The Maslach Burnout Inventory-Human Service Survey was used to assess burnout (MBIHSS). A multivariable logistic regression analysis was used to explore the potential determinants of burnout syndrome among the participants. A total of 251 healthcare professionals were included in this study making a response rate of 99.2%. The prevalence of burnout syndrome among healthcare professionals was 15.1% (95% CI [10.8, 19.9]). Being male (AOR = 3.22:95% CI [1.17, 8.87]), lack of interest in their profession (AOR = 2.66, 95% CI [1.84, 6.02]), experiencing physical violence (AOR = 3.52, 95% CI [1.32, 9.36]), unsatisfied with their job (AOR = 4.17, 95% CI [1.46, 11.90]) were variables found to be significantly associated with burnout syndrome. Burnout is a major problem among working in Dessie Comprehensive Specialized Hospital healthcare professionals. Being male, having no interest in their job, having physical violence, and not being satisfied with their job contributed to burnout syndrome. Interventions to increase interest in there in their job, improve physician-patient relationships, provide safer workplace environments, and increase job satisfaction may be promising strategies to reduce burnout syndrome.
Creating Awareness for Sustainable Goals: Reading Ruskin Bond’s Short Stories Through Bioregionalism Lenses
Authors: Parashar Archana , Baid Meeta , Chavda Mrunal
Published: December 2023

Sustainable Development Goals (SDGs) are evidence of the imbalance of human’s exploitation of nature through irresponsible consumption. This study has two purposes. First, it analyses how short stories and critical theories such as bioregionalism and ecocriticism can sensitize B-School learners to establish and sustain a lost relationship with nature. Second, it examines how establishing and reviving a solid relationship between purusha [human beings] and prakriti [nature] can help achieve SDGs through literature. To achieve these two aims, we critically examine Ruskin Bond’s short stories by employing the concept of bioregionalism. Our interpretation of the text and analysis of these stories showed strong connections between Bond’s short stories, bioregionalism and sensitizing readers. It was observed that if students are exposed to consuming such literature in their natural surroundings, it can increase their zeal to achieve SDGs. Incorporating literature in management education can raise awareness of responsible consumption as personal social responsibility.
Clinical Legal Education and Access to Justice During and Beyond COVID-19: Some Reflections of Indian Experience
Authors: Pandey Ajay , Chandra Sushant , Moti Shireen
Published: December 2023

Legal education aims to impart legal skills and training to law students and develop them into professionals who can render legal services. Clinical legal education (CLE) bridges the gap between the theory and practice of law. CLE has dual purposes of imparting lawyering skills to law students and achieving the social justice mission of law. CLE imparts certain skills and values to students for social justice. Students’ involvement in legal aid clinics makes them more justice-oriented, empathetic and ready for social change. With such orientation, they can assume larger leadership roles as ‘social engineers’. The access to justice crisis compels us to think about legal education’s scope and purpose. In this article, we argue that CLE is indispensable for the attainment of access to justice. During the COVID-19 pandemic, students supervised by clinicians at legal aid clinics worked with communities on issues of ‘migration’, ‘health’ and ‘education’. We argue that the COVID-19 pandemic was instrumental in revealing that legal aid clinics can play a larger role in the attainment of access to justice even during ‘normal times’. This article offers recommendations in order to achieve the goal of securing access to justice for the masses.
Lucky Me: Acknowledging Class Privilege on an Elite College Campus
Authors: Thornton Jack
Published: December 2023

A growing literature highlights the experiences of first-generation, low-income (FGLI) students on college campuses. However, these studies often conflate the positions of middle- and upper-class students. Using interviews with undergraduates at one elite institution, the author shows how upper-middle-class students responded to upward and downward cross-class encounters. Perceiving a status threat from above, students responded to interactions with rich peers through stereotypical denigration. Yet prolonged exposure to the rich resulted in another tactic, selective legitimation, which maintained that wealthy individuals who performed “awareness” could be morally rehabilitated. Encounters with FGLI classmates led respondents to view themselves as lucky or “privileged” for having escaped hardship, leading to rituals of deference aimed at muting the salience of class difference. Finally, despite their heightened recognition of class inequality, respondents drew equivalences between the problems of rich and poor students, ultimately denying the relevance of privilege in determining individual worth.
Relocating Yiddish voices: Narrative disfigurement and the “almost-lost” story in Edgar Hilsenrath’s holocaust novel Jossel Wassermanns Heimkehr
Authors: Twitchell Corey L.
Published: December 2023

My contribution to this special issue investigates how Holocaust survivor and German-Jewish author Edgar Hilsenrath’s 1993 novel Jossel Wassermanns Heimkehr (“Jossel Wassermann’s Homecoming”) adopts a narrative practice of voicing Yiddish-speaking Holocaust victims in a post-Holocaust context for the purpose of imagining fictional alternatives to the historical violence inflicted upon them. Using a narrative strategy that I term the “almost-lost” story, Hilsenrath creates a narrative universe in which Yiddish voices, if not the actual Yiddish speakers, can be collected and saved as “anti-data” by disembodied “Quasselstimmen” (German for “chatty voices”). Coupled with strategic narrative interruptions that surface through iterations of narrative disfigurement, Hilsenrath gives rise to narrative possibilities for Jewish resistance within the scope of a literary text. I demonstrate how attentive readers can identify through Hilsenrath’s highly complex narrative a signature for reconsidering the confluence of imaginative fiction and Holocaust history, emphasizing the reader’s ethical dilemma in encountering this history, while also considering how fiction can point us in new directions as we endeavor to pry open and better understand the full scope of atrocities committed against humanity in search for a renewed commitment to humanity and justice in the aftermath of genocidal violence.
A balance-theory analysis of xenosophia
Authors: Sternberg Robert J
Published: December 2023

Xenosophia—deep understanding of the other—is a noble goal to achieve. But it is a beginning toward wisdom, not an end. The balance theory of wisdom suggests a path forward for the world that is perhaps longer than that suggested by the construct of xenosophia. This article describes differences between wisdom viewed in large part as balance and wisdom viewed in large part as xenosophia.
Short-Term Substitution of Calcineurin Inhibitors (CNIs) with Recombinant Humanized Anti-CD25 Monoclonal Antibody (anti-CD25 rhMAb) As aGVHD Prophylaxis in Cnis Intolerant Patients after Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Shao Shan , Liu Huixia , Jiang Ying , Li Su , Wei Daolin , Zhu JUN , Wang Chun , Zhao Chuxian
Published: December 2023

Objectives: To investigate the efficacy of short-term substitution of Recombinant humanized anti-CD25 monoclonal antibody (anti-CD25 rhMAb) as aGVHD prophylaxis in CNIs intolerant patients after allogeneic hematopoietic stem cell transplantation (Allo-HSCT).

Methods: From August 2021 to August 2022, seventeen patients with refractory hematologic malignancies after salvage Allo-HSCT were enrolled in our study. All were treated with anti-CD25 rhMAb as GVHD prophylaxis due to severe CNIs intolerance such as acute renal dysfunction, central nervous system complications (CNSC) or endothelial injury syndromes. There were seven males and ten females, with a median age of 43 years (18-67). After the withdrawal of CNIs, anti-CD25 rhMAb was applied at 1mg/Kg once a week until the reinstitution of CNIs or mTOR inhibitors.

Results: Anti-CD25 rhMAb was initiated at a median of 5 days (range: 1-32) after HSCT. The median duration of substitution was 20(7-120) days. All achieved neutrophil engraftment after a median of 12 days (range: 10-17). Thirteen patients had platelet engraftment after a median of 13 days (range: 11-20). Four patients did not achieve stable platelet engraftment. Eight patients (47.1%) developed Grade II-IV aGVHD, and four (23.6%) developed Grade III-IV aGVHD. Only one patient died of aGVHD. Until December 31, 2022, Seven of 17 patients died. The longest follow-up time of the survivors was 347 days, and the median survival was not reached. Overall survival (OS) at six months was 62.6%. OS at six months was 80.0% in the subgroup with CNSC.

Conclusions: When CNIs intolerance occurs during Allo-HSCT, Short-term replacement of CNIs with anti-CD25 rhMAb is an optional approach, which may provide a promising aGVHD prophylaxis for patients with CNIs intolerance.
Utility of Echocardiogram in Neutropenic Patients with Gram Positive Bacteremia: A Retrospective Study
Authors: Sternbach Neta , Raanani Pia , Yahav Dafna , Shragian Liat , Yeshurun Moshe , Wolach Ofir , Ben zvi Haim
Published: December 2023

Introduction: Hemato-oncology patients are vulnerable to bloodstream infections (BSI) due to their immunocompromised and neutropenic state, and the common use of intravascular catheters. The risk of infective endocarditis (IE) among non-neutropenic patients with gram positive bacteremia is substantial, however the risk is considered to be lower among neutropenic patients, though data is limited. We aimed to evaluate the incidence of IE among neutropenic hemato-oncology patients' cohort, and to explore the yield of echocardiogram in this specific population.

Methods: A single center, retrospective study. Between 01/2007 and 12/2019, hospitalized patients in the Hematology department consisting of the hemato-oncology and bone marrow transplantation units were included, if they had positive blood cultures for specific organisms known to cause IE while neutropenic. Patient characteristics, results and timing of blood cultures and echocardiogram obtained during hospitalization were collected.

Results: Two hundred seventy-four patients had positive blood cultures with pathogens known to be associated with IE. Overall, 340 isolates have been identified. After excluding 57 coagulase negative staphylococcus (CONS) isolates which were suspected as a contamination (identified in a single collection), 241 patients were included with 283 isolates. CONS were the most commonly isolates found, followed by streptococcus viridans, comprising 31.4% (89) and 24.3% (69) of isolates, respectively. Trans thoracic echocardiography (TTE) was performed in 108 (45%) patients overall, of which 14 (5.8%) had additional trans esophageal echocardiogram (TEE).

Only one case of IE was diagnosed in our series, of a forty-seven-year-old female patient with a diagnosis of multiple myeloma in relapse after autologous stem cell transplantation. The patient presented with a stroke caused by septic emboli, fever and streptococcus viridans bacteremia. Lab works showed neutropenia of 0K/micl and thrombocytopenia of 8K/micl. TTE and TEE failed to demonstrate valvular pathology consistent with IE in this case. Valvular vegetations have not been identified on TTE nor on TTE in any other case as well.

Conclusion In our experience, the yield of echocardiogram in hemato-oncological neutropenic patients with gram positive bacteremia is extremely low, owing to reduced probability of IE in this population, and thus could be avoided in most cases.
Implementation and Evaluation of Discharge Planning for Patients Undergoing Umbilical Cord Blood Transplantation
Authors: Huang Lu , Zhu Yan , Wu Yun , Wang Yingying , Song Kaidi , Zhu Xiaoyu , Song Guiqi , Wu Yaohua , Zhang Yongliang
Published: December 2023

Purpose The purpose of this study was to implement discharge planning for patients undergoing umbilical cord blood transplantation (UCBT) and evaluate the effects on length of stay (LOS), hospital readmission, discharge readiness, self-efficacy, and quality of life (QoL).

Methods Participants (n =72) were assigned to a control group (CG: received usual care) or an intervention group (IG: received discharge planning from admission to 100 days after UCBT). LOS and the rate of hospital readmission within 30 days after discharge were collected. Discharge readiness was measured by the Readiness for Hospital Discharge Scale, self-efficacy and QoL were assessed at 100 days after UCBT using General Self-Efficacy Scale and FACT-BMT version 4.

Results Sixty-six patients completed the study, the IG group showed significantly better discharge readiness (p<0.05), improvement in self-efficacy (p<0.001). Except for social and emotional well-being, all the other dimensions and three total scores of FACT-BMT in the IG were higher than the controls (p<0.05). The LOS was less in the IG (50.12±8.80 vs. 53.28±11.28, p=0.207), the rate of hospital readmission within 30 days after discharge was lower (20.59% vs. 31.25%, p=0.376), however, the differences were not significant.

Conclusion This study provided the evidences on the implementation of discharge planning for patients undergoing UCBT, and suggested that nurse-led discharge planning should be incorporated into usual care for successful hospital-to-home transitions.
R-ISS Stage-Dependent Single-Cell Sequencing Analysis Uncovers Oncogenes and Potential Immunotherapeutic Targets in Multiple Myeloma
Authors: Zhong Ling , Luo Ji , Luo Lan , Yi Qing , Jiang Tao
Published: December 2023

Multiple myeloma (MM) accounts for ~10% of all haematologic malignancies. Little is known about high intratumour heterogeneities in patients stratified by the Revised International Staging System (R-ISS). Herein, we constructed a single-cell transcriptome atlas to compare differential expression patterns among stages. We found that a novel cytotoxic plasma cell (PC) population exhibited with NKG7 positive was obviously enriched in stage II patients. Additionally, a malignant plasma cell population with significantly elevated expression of MKI67 and PCNA was associated with unfavourable prognosis and Epstein-Barr virus (EBV) infection in our collected samples. Moreover, Ribonucleotide Reductase Regulatory Subunit M2 (RRM2) was found and verified to promote proliferation of MM cell lines, suggesting RRM2 may serve as a detrimental marker in MM. The percentages of CD8+ T cells and NKT cells decreased along with R-ISS stages, reflecting the plasticity of the tumour immune microenvironment. Importantly, their crosstalks with myeloid cells and PC identified several potential immunotargets such as SIRPA-CD47, and CD74-MIF, respectively. Collectively, this study provided an R-ISS-related single-cell MM atlas and revealed the clinical significance of novel PC clusters, as well as potential immunotargets in MM progression.
Azacitidine Combined with Interferon α for Preemptive Treatment of AML/MDS after Allogeneic Peripheral Blood Stem Cell Transplantation：a Prospecitive Phase II Study
Authors: Huang Chongmei , Yang Jun , Tong Yin , Qiu Huiying , Zhou Kun , Xia Xinxin , Zhang Ying , Shen Chang , Wan Liping , Song Xianmin
Published: December 2023

Objective : this study investigated the efficacy and safety of azacitidine and interferon α preemptive treatment in the post-transplant in patients with AML/MDS. Methods: between Octorber 1, 2019 and July 31, 2022, a total of 49 patients aged 17 to 62 years were enrolled into this prospective clinical study of post-transplant azacitidine combined with interferon α preemptive treatment. Patients with minimal residual disease (MRD) positive and / or mixed chimerism were scheduled to receive azacitidine, given as 32 mg/m 2 per day subcutaneously for 5 days, and interferon α 3 million units/m 2 per day from 8th day and continued for 28th day for 1 cycle. Results: patients who acquired treatment response were 34 (69.4%), of which turned MRD-negative and obtained complete chimerism were 22 (44.9%) and 5 (10.2%) at 1 cycle, respectively. Median follow-up time after preemptive intervention was 440(range, 45 to 927) days. Cumulative incidences of relapse (CIR) and no relapse mortality (NRM) were 36.7% and 4.1%, respectively. Probabilities of event-free survival (EFS) and overall survival (OS) were 55.1% and 71.4%, respectively. The most common adverse events were graft-versus-host disease (GVHD) (38.8%), liver toxicity (46.9%) and neutropenia (28.6%). Conclusion: these data support the notion that azacitidine combined with interferon α is better used as the preemptive therapy against relapse tendency for patients after allo-HSCT performed for AML/MDS. Side effects were mainly GVHD, reversible cytopenia and hepatic toxicity. This prospective trial in the post-transplant setting was feasible and safe but challenging. This trial was registered at www.clinicaltrials.gov as#NCT04078399.
Factors Associated with in-Hospital Mortality in Patients with Burkitt Lymphoma - Analysis of the National Inpatient Sample (NIS)
Authors: Pichardo Rayli , Ramo Aula , Abu Omar Yazan , Dabak Vrushali S.
Published: December 2023

Introduction

Burkitt Lymphoma (BL) is a highly aggressive B-cell non-Hodgkin Lymphoma, characterized by translocation and dysregulation of the MYC gene. BL comes in three distinct forms: endemic, sporadic, and immunodeficiency-related. BL has become a highly curable disease after the development of intense chemo-immunotherapy regimens, but given the low incidence of the disease, nationally representative studies on outcomes are scarce. We aim to highlight the most recent population-based factors associated with inpatient mortality and morbidity in patients with Burkitt's lymphoma.

Methods

The National Inpatient Sample database was queried from October 2015 to December 2020.

Adults aged >= 18 with a primary diagnosis of BL were identified and stratified into those with and without the outcome of mortality. Complications included were queried using ICD codes most commonly found in the secondary diagnosis variables. Baseline characteristics, inpatient complications, and outcomes were compared using chi-squared and Wilcoxon rank-sum tests. Logistic regression analysis was performed to assess the risk of death before and after adjusting for multiple risk factors.

Results

We found 3,650 admissions with a primary diagnosis of BL, of which 320 (8.8%) patients died during the hospitalization. Patients who died had higher Charlson Comorbidity Index (CCI) >=3 (69%), tumor lysis syndrome (TLS) (41%), Sepsis (39%), and acute hypoxic respiratory failure (AHRF) (33%). No significant differences were found according to income, hospital bed-size or geographical region. In univariable analysis patients who died tended to be older with age >= 65 years (OR 2.55 (1.23 to 5.26) p=0.039), however, once adjusting for other variables there was no significant difference in mortality by age group, race, or gender. Multivariable analysis identified 3 factors with high association with mortality: acute renal failure (OR 3.07 (1.63 to 5.76), p<0.001), sepsis (OR 7.96 (3.85 to 16.4), p<0.001), and acute hypoxic respiratory failure (OR 2.70 (1.23 to 5.92), p=0.013).

Conclusion

BL remains a highly aggressive but potentially curable disease in patients able to tolerate intensive chemo-immunotherapy regimens. Our study highlights multiple factors that are independently associated with death include acute renal failure, sepsis, and acute hypoxic respiratory failure. Close monitoring should be placed on patients with the above complications to improve survival.
Metabolomics-Driven Systematic Research Reveals Different Metabolomic and Lipidomic Profiling of Bone Marrow Plasma in Patients with Multiple Myeloma
Authors: Zhu Ziang , Li Yang , Li Jin-Yuan , Huang Han-Ying , Shuzhao Chen , Liu Yang , Liang Yang , Shu Lingling
Published: December 2023

Myeloma cells resident in bone marrow (BM), therefore the microenvironment plays critical roles in the invasion, proliferation and migration. Obesity increases the morbidity and drug resistance in patient of multiple myeloma (MM) through changing the bone marrow environment. Extracellular environments such as the BM plasma likely have unique lipidomic metabolite profiles that predicts the prognosis in patients with multiple myeloma. However, the study of multiple omics on metabolic changes in BM of MM patients are still very limited.

The present study utilized an untargeted metabolite and targeted complex lipid profiling (Liquid chromatography-mass spectrometry, LC-MS) analysis to identify significant differences in the metabolite levels of BM plasma between newly diagnosed MM patients with different BMI (≤24 kg/m 2, n = 10; ≥25 kg/m 2, n = 10). This was followed by verification of some of the metabolite differences of interest by targeted quantification of the metabolites using isotopic internal standards in the exploratory cohort as well as an independent validation cohort.

Significant differences were noted in the amino acid profiles, lipid metabolism and amino sugar metabolism, such as increased L-Glutamate, L-Proline, D-Proline, palmitoleic acid and D-Fructose, etc between MM patients with different BMI ( Figure A-C). Glycerol phosphate shuttle, glycerolipid metabolism and de novo triacylglycerol biosynthesis were the top 3 enriched signaling pathways in BM of obese MM patients ( Figure D). Targeted complex lipid profiling analysis further showed that triglyceride (TG)，diglyceride (DG) were increased notably in obese BM plasma of MM patients and correlated significantly with BMI ( Figure E-G). Glycerolipids, triradylglycerols, diradylglycerols and fatty acyls metabolism were enriched in obese group by GSEA analysis ( Figure H). Furthermore, KEGG enrichment analysis showed differentiate expressed lipid metabolites in BM plasma of obese MM patients comparing to that of lean group, including regulation of lipolysis in adipocytes, glycerolipid metabolism, fat digestion and absorption, cholesterol metabolism and metabolic pathways, etc ( Figure I ).

In summary, metabolite and complex lipid profiling of the BM plasma identifies differences in levels of metabolites and lipids between MM patients with different BMI. This may provide insight into the explanation that obesity increases the susceptibility to MM and drug resistance.

Acknowledgement

This project is supported by the Sun Yat-sen University Hundred Talents Program (PT19200101), Natural Science Foundation of Guangdong Province (2022A1515010290).
Efficacy and Safety of Avatrombopag in the Treatment of Thrombocytopenia after Umbilical Cord Blood Transplantation
Authors: Huang Aijie , Sun Guangyu , Tang Baolin , Song Kaidi , Cheng Yaxin , Tu Meijuan , Wu Yue , Pan Tianzhong , Wang Dongyao , Zhu Xiaoyu
Published: December 2023

Background: Delayed platelet engraftment is a common complication after umbilical cord blood transplantation (UCBT), and it has no standard therapy. Avatromboapg is a second generation thrombopoietin receptor agonist (TPO-RA) and showed efficacy in immune thrombocytopenia (ITP). However, few reports focused on its efficacy in patients diagnosed with thrombocytopenia after allogeneic hematopoietic stem cell transplantation (allo-HSCT).

Methods: We conducted a retrospective study to evaluate the efficacy of avatrombopag in 69 patients after UCBT as the first-line thrombopoietin receptor agonist (TPO-RA) treatment.

Results: Sixty-one patients were given avatrombopag to promote platelet engraftment, the other 8 for secondary failure of platelet recovery (SFPR). For the majority of patients (44/69, 63.8%), the initial dose was 40 mg daily. Among the 61 patients given avatrombopag for platelet engraftment, 40 achieved an overall response (OR) (65.6%), and the cumulative incidence of OR was 76.2% (95% CI, 61.3-86.0), at a median time of 23 days (range, 3-131 days). Thirty-eight of 61 (62.3%) patients achieved complete remission (CR), and the cumulative incidence of CR was 76.2% (95% CI, 61.1-86.1). Patients suffering from SFPR had a better cumulative incidence of OR [100% (95% CI, NA), P = 0.005]. Giving avatrombopag before 37 days post-UCBT was beneficial for OR in multivariate analysis.

Conclusion: In summary, our results indicate that avatrombopag could be used to promote platelet engraftment, especially in the early period (< 37 days after UCBT). Patients with SFPR may have a better response to avatrombopag therapy.

Keywords: Avatrombopag; umbilical cord blood transplantation; thrombopoietin receptor agonist; secondary failure of platelet recovery

Conflict-of-interest disclosure: The authors declare that they have no competing interests.
Unveiling Gender Disparities: Female Authorship in Pivotal Trials for US Food and Drug Administration (FDA)-Approved Novel Chimeric Antigen Receptor T-Cell Therapies
Authors: Farooq Muhammad , Sohail Aruba , Khan Sara , Ukrani Janta , Zahid Ibrahim , Hassan Maryum , Jaglal Michael V.
Published: December 2023

Introduction

CAR-T cell therapy, an FDA-approved breakthrough in hematologic malignancy treatment, has emerged as a game-changer through rigorous pivotal trials. Reportedly, women were underrepresented as authors in pivotal trials supporting approval of novel hematological drugs [1]. However, gender inequity in authorship across pivotal trials of FDA-approved novel CAR-T cell therapies remains unexamined. Thus, our study explores gender representation among authors in pivotal trials that led to the first-ever FDA approval of CAR-T cell therapies for hematological malignancies

Methods

Drugs@FDA portal was searched for novel CAR-T cell therapies approved between 2015 and 2022. Drug approval labels were searched to identify all pivotal trials listed in Section 14 under “Clinical Studies.” Only pivotal trials with corresponding trial publications were included in this study. The gender of trial authors was captured as binary (women and men) and was identified by using the Genderize software (Demografix ApS) or by verifying personal pronouns on authors' institutional profiles or other sources. Study-level estimates for the proportion of women authors were pooled using the DerSimonian and Laird random-effects meta-analysis of proportions model. Analyses were conducted with OpenMeta [Analyst] software version 10.12.

Results

From 2017-2022, the FDA approved a total of 6 novel CAR-T cell therapies, corresponding to 6 trials and 7 trial publications (755 participants) that were included in the study (Table 1). One trial's findings were reported in two distinct publications. A total of 201 authors were screened, and 1 was excluded because of the inability to assign author gender. Genderize was used to identify the gender of 177 authors; 152 were further confirmed by checking personal pronouns. Of the 24 authors with a prediction probability estimate less than 90.0% on Genderize, author gender was identified for 23 by using personal pronouns listed in institutional profiles or other sources.

The median number of men and women authors of trial publications was 19 (IQR, 15-23) and 9 (IQR, 6-11), respectively. The overall proportion of women authors was 29.6% (95% CI, 20.5%-38.7%). The proportion of women authors varied significantly across the 7 trial publications (p-heterogeneity = 0.043). The proportion of women as first and senior authors was the same, estimating about 14.3% (95% CI, 0.0%-40.2%).

Conclusions

Our study highlights gender disparities in the authorship of pivotal efficacy trials supporting the FDA approval of novel CAR-T cell therapies. This underscores the urgent need for institutions to devise tailored policies that tackle the unique challenges faced by women in the medical field, while fostering an inclusive and supportive workplace environment that empowers women to achieve academic success.
Real-World Study of Polatuzumab Vedotin-Based Regimen for Relapsed or Refractory Diffuse Large B-Cell Lymphoma in Chinese Cohort: Updated Results of 2-Year Follow-up
Authors: Wu Jianqiu , Li Fei , Wuxiao Zhi-Jun , Tang Weiyan , Teng Yue , Liu Yanyan , Chu Han , Wu Zhiya , Shen Yiwen , Kong Fancong , Yao Zhihua , Zhou Weilun , Feng Jifeng
Published: December 2023

Introduction

Patients with relapsed or refractory (r/r) DLBCL had poor prognosis when ineligible to autologous hematopoietic stem cell transplantation (auto-HSCT). Polatuzumab vedotin (Pola) has demonstrated significant efficacy and acceptable safety in such patients in Clinical trials and real-world data. Here we reported long-term follow-up result of Pola-based regimen in real-world Chinese cohort.

Aims

To evaluate the efficacy and safety of Pola-based regimens for the treatment of r/r DLBCL using real-world data.

Methods

This retrospective study analyzed data from the Chinese Pola compassionate use program, conducted at four tertiary hospitals from December 2019 to June 2021. Patients with r/r DLBCL were enrolled. The treatment regimens included Pola in combination with rituximab (Pola+R) or with additional bendamustine (Pola+BR) administered for six cycles, with each cycle lasting 21 days. The objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and adverse events (AEs) were analyzed.

Results

Thirty-nine patients were included in the analysis, with a median follow-up of 23.5 months (range: 0.6-35.2). The ORR at the end of treatment was 38.5% (15/39), while the best ORR achieved was 69.2% (27/39). The median PFS and OS were 6.6 months (95%CI: 3.7-9.6) and 15.6 months (95%CI: 3.4-27.9), respectively. Compared to those who did not complete six cycles of treatment, a significantly longer PFS (12.1 vs. 3.5 months, P=0.006) and OS (18.8 vs. 6.3 months, P=0.001) was observed in patients who completed all six cycles of treatment. Among 16 patients receiving Pola+R and 23 receiving Pola+BR, the proportion of patients who completed all six-treatment cycles was 56.3% and 34.8%, respectively. Grade 3-4 AEs were reported in 48.7% of patients with most commonly occurred being neutropenia (28.2%), leucopenia (17.9%) and thrombocytopenia (15.4%).

Conclusions

The 2-year follow-up analysis demonstrated sustained progression-free and overall survival, with no new safety signals. The full cycles of Pola-based regimen may contribute to better efficacy for real-world populations. These findings supported Pola-based regimens as an effective real-world treatment option for Chinese patients with r/r DLBCL.

Key words

Diffuse large B-cell lymphoma; refractory/relapsing; polatuzumab vedotin; real-world study; China.
A Study on Heterogeneity and Early Response to Chemotherapy in Pediatric ETV6-RUNX1 Positive Acute Lymphoblastic Leukemia By RNA-Seq Expression Profile
Authors: Zheng Xueling , Zhou Chunyu , Zhang Ruidong , Gao Chao , Han Jingdong , Wang Tianyou , Zheng Huyong
Published: December 2023

Objective

ETV6-RUNX1 positive ALL is the most common type in childhood acute lymphoblastic leukemia(ALL), and it is also a type with good prognosis. However, there are still recurrent or refractory cases in this type, and there is still heterogeneity among individuals.In this research, we investigate the heterogeneity of ETV6-RUNX1 positive ALL in children by RNA-seq expression profile, and to explore the early response to chemotherapy and microenvironment characteristics of different clusters, so as to provide evidences for the exploration of genetic high-risk factors and clinical personalized diagnosis and treatment of such children.

Method

From September 2019 to June 2021, 72 children with newly diagnosed ETV6-RUNX1 positive ALL in standard risk group were enrolled and treated with CCLG-ALL-2018 chemotherapy protocol, which were all detected by RNA-seq technology. The sequencing results were analyzed by cluster analysis and bioinformatics analysis. We explored the early response to chemotherapy and microenvironment characteristics of the different clusters.

Result

ETV6-RUNX1 positive ALL were divided into three groups according to the RNA-seq expression profile including 16 cases (22.2%) in ER1 group, 35 cases (48.6%) in ER2 group and 21 cases (29.2%) in ER3 group. The number of patients with co-negative minimal residual disease (MRD) by flow cytometry (MRD-FCM) and next-generation sequencing (MRD-Gene) on the 15th day of chemotherapy in ER1 and ER3 groups was significantly different (3/16 vs. 13/21, P=0.0178), while there were 17 cases (17/35) with co-negative MRD in ER2 group after fifteen-day chemotherapy. It showed that the proportion of NK cells ( P=0.056) and CD8 + T cells ( P=0.047) in peripheral blood in ER1 group were both higher than those in ER3 group. Compared with ER3 group, ER1 group showed low expression of RPL41 and high expression of MRPS28 and SERPIND1, which were mainly involved in stress, proliferation and drug resistance of cells and the differentiation of hematopoietic stem cell. In addition, ER1 group showed lower expression of ribosome-related genes and higher activation of mTOR pathway than ER3 group.

Conclusion

The heterogeneity in gene expression profile were presented in children with ETV6-RUNX1 positive ALL. Compared with ER3 group, patients in ER1 group may have a poorer early response to chemotherapy with a relatively higher risk due to the stronger proliferation and drug resistance of leukemic cells probably. For patients in ER1 group, even if MRD is negative on the 15th day of themotherapy, it may be necessary to strengthen the observation of early response and consider the treatment for escalated risk in time.
Hyperammonemic Encephalopathy in Multiple Myeloma: Systematic Review and Case Series
Authors: el Ghoubaira Joseph , Alsouqi Aseel , Farah Rafic J
Published: December 2023

Objectives: To better understand the presentation and clinical outcomes of hyperammonemic encephalopathy in multiple myeloma, we report 3 cases from our institution and present 55 published cases from the literature.

Background/Intro: Hyperammonemia is a rare but life-threatening complication of multiple myeloma with poor survival despite treatment. Little is known about the clinical presentation and outcomes of patients suffering from this entity. We hereby report a systematic review and a meta-analysis of cases with hyperammonemic encephalopathy.

Methods: Case reports and case series were identified using the Medline database, as well as PubMed search engine. Clinical and pathological data were collected and stratified by demographics and treatment. The data was further analyzed using SPSS.

Results: A total of 58 patients were included in the study. The mean age of the affected patients was 64.4 years, male to female ratio was 1.15:1. The median ammonia level measured was 123 μmol/L. Stage III disease was most prevalent in reported cases (89%). Most common MM subtype was IgG (38%) followed by IgA (36%). Thirty-seven patients (64%) had relapsed disease, while 17 (29%) were new diagnoses. Overall, 35 out of 58 (60%) patients died while being treated as inpatients. Chemotherapy was the only variable associated with an improved survival with p-0.02.

Conclusion: Hyperammonemia in the setting of multiple myeloma is an uncommon complication. It is associated with poor prognosis. Treatment should begin as soon as the diagnosis is confirmed with myeloma directed therapy in order to improve survival.
Multicenter Open Label Phase 2 Study of Quadruplet-Based Regimen Iskpd (isatuximab plus pomalidomide and dexamethasone with carfilzomib) in Early Relapsed or Refractory Multiple Myeloma - IFM2018-03
Authors: Bobin Arthur , Lambert Jerome , Ragot Stéfanie , Perrot Aurore , Manier Salomon , Karlin Lionel , Caillot Denis , Benboubker Lotfi , Chalopin Thomas , Araujo Carla , Fontan Jean , Braun Thorsten , Mariette Clara , Scherman Elodie , Decaux Olivier , Blade jean Sebastien , Keddar Faiza , Roul Christophe , Dib Mamoun , Corre Jill , Orsini Piocelle Frederique , Vincent Laure , Touzeau Cyrille , Moreau Philippe , Avet Loiseau Herve , Leleu Xavier
Published: December 2023

Background. RRMM (relapsed or refractory multiple myeloma) is associated to shortened OS (survival) with subsequent relapses and needs optimized treatment approaches. The current treatment paradigm is based on triplet-based association of antiCD38 immunotherapy (antiCD38 IT) with either Imids (Pomalidomide) and dexamethasone or proteasome inhibitors (PI) such as Carfilzomib and dexamethasone. However, quadruplet-based regimens (antiCD38 immunotherapy +Imids +PI +dexamethasone) have transformed the treatment landscape in the upfront setting, improving MRD (minimal residual disease) and survival.

We hypothesized that a quadruplet-based regimens (antiCD38 immunotherapy +Imids +PI +dexamethasone) would further improved MRD and survival in early RRMM. We describe a phase II multicentric, open-label study, of isatuximab, pomalidomide and dexamethasone plus carfilzomib (IsKPd/ IFM2018-03, NCT04287855) for patients with early RRMM.

Study design and Methods. Approximately 90 patients will receive the association of isatuximab, pomalidomide and dexamethasone with carfilzomib (IsKPd), and the study has fully enrolled 82 patients as of January 2023. Eligible patients are adults aged ≥18 years old with RRMM previously treated with 1 or 2 lines of therapy, including lenalidomide, prior to the study entry. Patients were excluded if they were refractory to any anti-CD38 monoclonal antibody or to carfilzomib, or if they were previously exposed to pomalidomide. Isatuximab will be given by IV route at 10 mg/kg on days 1, 8, 15, and 22 of cycle 1, on days 1 and 15 from cycle 2 to 12 and on day 1 only from cycle 13, 28-day cycles. Carfilzomib will be given by IV route at 20/27 mg/m² on days 1-2, 8-9, 15-16 during cycle 1, at 56mg/m² on days 1, 8, 15 from cycle 2 to 13 and at 56mg/m² on days 1 and 15 after cycle 13. Pomalidomide will be administered by oral route at 3 mg daily on days 1 to 21 in cycle 1 and at 4 mg daily from cycle 12. Dexamethasone will be given by oral route at 40/20 mg daily on days 1, 8, 15 and 22. The primary objective is to evaluate the MRD rate at 10-5 in patients with RRMM treated with IsKPd. Patients will pursue Isa-KPd until progression or unacceptable toxicity. Key secondary objectives include the survival analysis (OS, PFS, EFS, TTNT), response rates and duration of response and evaluation of the safety profile.

The study is expected to read out in January 2024 with sustained MRD reported.