bluuebunny/crossref_metadata_2025 huggingface dataset:
Single-Cell Analyses Unveil a Potential Mechanism Promoting Graft-Versus-Leukemia Response in Haploidentical Transplantation Using Peripheral Stem Cells Plus Cord Blood Grafts through Early Immune Reconstruction of CD8+ Infg+ T Cells
Authors: Yu Sijian , Liu Qifa , Xu Xi , Liu Qiong , Qiu Guo
Published: December 2023

Abstract

Background

Haploidentical donor stem cell transplantation (haplo-SCT) by using G-CSF-primed peripheral stem cells combined with bone marrow grafts (PBSC+BM) represents a widely employed strategy for acute myeloid leukemia (AML). While leukemic relapse is one of the main reasons for the failure of SCT. Surprisingly, our clinical data found that haploidentical peripheral stem cells combined with cord blood (haplo-PBSC+cord) transplantation had significantly lower incidence of relapse than haplo-PBSC+BM transplantation. Nonetheless, the underlying mechanism needs to be explored.

Method

From 2021 to 2022, bone marrow samples at 1 and 3 months post-transplantation from 4 AML patients who underwent haplo-PBSC+cord transplantation and 3 AML patients who received haplo-PBSC+BM transplantation were obtained. We used single-cell RNA-sequence (scRNA-seq) technology for analysis of hematopoietic reconstitution disparity between the PBSC+cord and PBSC+BM groups.

Results

Significant disparities manifest in the initial stages of hematopoietic reconstitution between the PBSC+cord and the PBSC+BM groups. Notably, at 1 month and 3 months post-transplantation, the PBSC+cord group demonstrated conspicuous reconstitution of lymphoid and erythroid cells, with CD8+ T cells exhibiting the most pronounced effect. Differential gene analysis revealed that T cells in the PBSC+cord group display elevated expression of graft-versus-leukemia (GVL)-related cytokines, including IFN-γ, CCL3, and IL1B, when compared to the PBSC+BM group. Furthermore, noteworthy differences in T cell subsets were observed between the two groups. Within 1 month and 3 months post-transplantation, the PBSC+cord group experienced up-regulation of CD8+ effector memory T cells (TEM), characterized by heightened expression of the IFNG gene. Gene Set Variation Analysis (GSVA) unveiled significant enrichment of CD8+ IFNG+ TEM in T cell activation, cytotoxicity, cytokine secretion, and other pathways, suggesting its potential GVL effect. On the contrary, the PBSC+BM group demonstrated a higher proportion of CD4+ T cells, γδT cells, and MAIT cells at 1 month and 3 months post-transplantation. Among CD8+ T cells, the PBSC+BM group showcased a more robust reconstruction of CD8+ TIGIT+ T cell subsets, which highly express exhaustion-related genes like TIGIT, LAG3, PDCD1 (PD-1), HAVCR2 (TIM-3), and exhibited increased apoptosis-related pathway activity.

Conclusion

Our investigation identified a potential mechanism promoting GVL response in the immune reconstitution of haplo-PBSC+cord transplantation.
Young and Distinct: Clinical Characteristics and Outcomes of Patients 50 or Younger with Multiple Myeloma
Authors: Tufano-Sugarman Andrea , Islam Shahidul , Davies Faith E. , Morgan Gareth J. , Kaminetzky David , Braunstein Marc
Published: December 2023

Introduction: Multiple Myeloma (MM) presents at a median age of 69. Patients age 50 or younger represent only 10% of diagnoses and are less well-characterized. Some studies have suggested that younger MM patients are more likely to present with lytic lesions, be IgD subtype, have high-risk cytogenetics, and have relatively improved survival. We aimed to characterize this understudied population in the modern era.

Methods: We conducted a retrospective chart review of patients age <50 meeting IMWG criteria for symptomatic MM treated across our institution's cancer center network between 2010 and 2023. Overall survival was defined as time in months from diagnosis to last follow-up or death. Time to relapse after transplant was captured.

Results: We identified 97 younger MM patients, with a median age of 44 (range 26-50). Males and females represented 50.5% and 49.5% of cases respectively. Complete demographics are listed in the table. The most common MM subtype was IgG Kappa (40%), and 23% had light chain-only disease. Incidentally found cases, defined as abnormalities on imaging or labs ordered for another reason, represented 11% of cases. 61% of patients presented with a skeletal issue such as bone pain and/or pathologic fracture. Presenting features are described in the table. At time of diagnosis, 77% of patients were found to have lytic lesions. Few patients had previously identified MGUS (3%) or smoldering MM (5%). Regarding cytogenetics, 18% had one or more high-risk features. The most common frontline treatment was VRD. As shown in the table, 66% and 29% received 3 and 4 drug induction regimens respectively. Of note, 91% were referred for autologous stem cell transplant (ASCT), and 72% proceeded. 4 patients were deceased at the time of analysis. Survival for the entire population was 95.9% at a median follow up time of 65.5 months. In the patients who underwent ASCT, 41.2% relapsed with median progression-free survival of 57 (44-71) months.

Conclusions: MM patients age <50 were found to be distinct from the known characteristics of the general population in several notable ways. There was equipoise among demographic features, with a nearly equivalent prevalence in males and females, and similar median ages across racial groups. We found a greater enrichment of light chain disease than expected, but less renal dysfunction at presentation. IgD subtype does not appear increased in this population. Younger patients do not appear more likely to have high risk cytogenetics. Lastly, survival for younger patients was higher compared to the reported 5-year survival of MM, which may be explained by the finding that these patients were treated primarily with triplet or quadruplet anti-myeloma regimens and often proceeded to ASCT.
Repressing HIF-1α-Induced HDAC9 Contributes to the Synergistic Effect of Venetoclax and Menin Inhibitor in KMT2Ar AML
Authors: Ling Qing
Published: December 2023

Background: MLL-rearranged acute myeloid leukemia (MLLr-AML) is one aggressive subtype of AML, and is conferred one extremely poor prognosis under the current therapeutic strategy. Up to now, it still lacked one effective treatment to maintain the long-term survival for patients with MLLr-AML, while the developments of targeted therapy brought hopes. At present, the star drug BCL-2 inhibitor Venetoclax combined with Azacitidine (AZA) or low-dose Cytarabine (LDAC) has become the first-line scheme for elderly AML, which is not beneficial for MLLr-AML patients. So we are committed to finding a more suitable partner for VEN because MLLr-AML is very sensitive to VEN in vitro studies. The MLL-menin complex is crucial for maintaining MLLr-AML, and the research and application of MLL-menin inhibitors (MEN1i) is currently one of the hotspots in the AML field. Therefore in this study, we aimed to uncover the synergistic effect and mechanism of MEN1i combined with Venetoclax in treating MLLr-AML.

Methods: Cell culture and transfection, Cell proliferation, apoptosis and Cell cycle assay, Quantitative RT-PCR, and Western blotting analysis were used to explore biological phenotypes. RNA-seq profiling was performed for DMSO, VEN, MEN1i, and combination of VEN and MEN1i groups in three MLLr-AML cell lines MV4-11, MOLM13, THP-1. Bioinformatic tools were used for differential analysis.

Results: MLLr-AML cells were sensitive to VEN or MEN1i monotherapy, and the combination of two drugs had a strong synergistic effect in vitro and in vivo. Furthermore, we found that combination of VEN and MEN1i significantly enhanced apoptotic induction to influence the MLLr-AML survival. To uncover the synergetic mechanism of VEN and MEN1i, we displayed RNA-Sequencing for DMSO, VEN, MEN1i, and combination of VEN and MEN1i groups in three MLLr-AML cell lines MV4-11, MOLM13, THP-1. Finally we found that repressing HIF-1α-induced HDAC9 contributes to the synergistic effect of Venetoclax and MEN1i in MLLr-AML.

Conclusion: VEN combined with MEN1i had a strong synergistic effect in the treatment of MLLr-AML. Repressing HIF-1α-induced HDAC9 contributes to the synergistic effect of Venetoclax and MEN1i in MLLr-AML.
Efficacy and Safety of Low-Dose Venetoclax Combined with Voriconazole Inpatients with Acute Myeloid Leukemia Unfit for Intensive Chemotherapy
Authors: Meng Danchen , Ruan Min , Liu Xinyao , Wu Wei , Zhuang Junling , Ge Jian , Huang Zhenqi , Long Zhangbiao
Published: December 2023

Background: Venetoclax combined with hypomethylating agents is the standard regime for elderly patients with acute myeloid leukemia unfit for intensive induction therapy. Nevertheless, many patients struggle with finances and forgo treatments due to the high costs of venetoclax. Concurrent application of venetoclax and CYP3A4 inhibitors such as voriconazole in low-income patients maybe is a feasible strategy to reduce the dose of ventoclax.

Methods: We conducted a single-institutional, non-randomized, open-label, prospective study. Between June 2020 and March 2023, 57 elderly or unfit patients with newly diagnosed acute myeloid leukemia at the first affiliated hospital of Anhui medical university were enrolled. Twenty-three patients received low-dose venetoclax plus voriconazole plus azacitidine (cohort 1), whereas another 34 patients received standard dose venetoclax plus azacitidine (cohort 2). The efficacy of the two regimes between cohorts was analyzed and compared, the peak venetoclax concentration (C max) and side effects of the patients were also detected.

Results: Totally, there were 35 males and 22 females, with a median age of 67 (range 46-91) years old. 86% (49/57) of patients were adverse/intermediate risk in the whole cohort. The baseline characteristics were all balanced differently between the two cohorts. The venetoclax Cmax in cohort 1 was 1930±225ng/mL, whereas the venetoclax Cmax in cohort 2 was 2371±274ng/mL, there was no significant difference between the two cohorts ( P＝0.3138). The overall response rates were 91% (21/23) and 85% (29/34) in cohort 1 and cohort 2, respectively ( P＝0.0834). At a median of 16 months of follow-up, the median progression-free survivals were 16 and 12 months in two cohorts, respectively ( P＝0.2651) with a hazard ratio of 0.6507. The median overall survivals were not reached and 14 months in the two cohorts, respectively ( P＝0.4636) with a hazard ratio of 0.7466. The most common hematological adverse events were neutropenia, thrombocytopenia, and anemia, whereas the most frequent non-hematological adverse events include infections, vomiting, diarrhea, and hypokalemia.

Conclusions: The combination of low-dose venetoclax and voriconazole is well tolerated and effective in unfit AML patients. Concurrent application of venetoclax provided a feasible and sustainable strategy for low-income patients.

Keywords: Venetoclax, low-dose, voriconazole, Unfit, Acute myeloid leukemia
Super-Enhancer-Driven IGF2BP2 and IGF2BP3 Promote DDX21 Expression in Acute Myeloid Leukemia
Authors: Zhao Yanchun , Jin Jie
Published: December 2023

Background : Acute myeloid leukemia (AML) is a hematological malignancy with a median overall survival (OS) of 8.5 months and a 5-year OS rate of 24.0%. Considering that relapse and drug resistance are major obstacles affecting the survival of AML patients, it is urgent to investigate the deeper pathogenesis of AML. Epigenetic modifications are extensively involved in the leukemogenesis of AML, especially N6-methyladenosine (m 6A) RNA methylation and super-enhancers (SEs). However, the relationship between m 6A and SEs in AML has not been elucidated.

Methods : Chromatin immunoprecipitation (ChIP) sequencing data from Gene Expression Omnibus (GEO) cohort were analyzed to search SE-related genes. The mechanisms of m 6A-binding proteins IGF2BP2 and IGF2BP3 on DDX21 were explored via methylated RNA immunoprecipitation (MeRIP), RNA immunoprecipitation (RIP) and luciferase reporter assays. The potential roles of DDX21 in AML were verified through functional assays in vitro and in vivo.

Results: Two SE-associated genes, IGF2BP2 and IGF2BP3, were identified in AML. There were high enrichment of H3K27ac, H3K4me1 and BRD4 in IGF2BP2 and IGF2BP3. BRD4 inhibitor JQ1 or BRD4 knockdown could lead to the suppression of IGF2BP2/3 expression, indicating the activation by SE machinery on the transcription of IGF2BP2/3. As m 6A-binding proteins, IGF2BP2 and IGF2BP3 enhanced the stability of DDX21 mRNA in an m 6A-dependent manner. DDX21 was highly expressed in AML patients, and elevated DDX21 expression suggested a poor survival. Functionally, DDX21 deficiency inhibited proliferation, facilitated apoptosis and arrested cell cycle of AML cells in vitro . I n vivo, knockdown of DDX21 substantially reduced tumor load and prolonged survival of recipient mice.

Conclusions: Dysregulation of SE-IGF2BP2/IGF2BP3-DDX21 axis promotes the progression of AML, which paves the way to develop more effective therapeutic strategies.
Clime: CLL Immune Micro-Environment and Risk of Infections Pre- and Post-Diagnosis: A Population-Based Study
Authors: Banerji Versha , Dawe David E , Xue Lin , Bucher Oliver , Yang Lin , Johnston James B. , Gibson Spencer Bruce , Decker Kathleen
Published: December 2023

Background: Immune dysfunction precedes a diagnosis of chronic lymphocytic leukemia (CLL) in some patients. More information is needed about which patients experience immune dysfunction and how it impacts disease progression, as well as the development of post-diagnosis infections and second malignancies. The objectives of this study were to 1) examine the rate of pre-diagnosis infection for individuals diagnosed with CLL compared to population controls, 2) evaluate the impact of pre-diagnosis infection on time to first treatment, 3) compare the rate of immune dysfunction before the start of treatment by stage, and 4) compare the rate of immune dysfunction before the start of treatment for each year post-treatment.

Methods: We used a retrospective matched cohort study design that included all individuals in Manitoba diagnosed with CLL from 2006 to 2019. Individuals were identified from the Manitoba CLL database and the Manitoba Cancer Registry (MCR). Individuals with CLL were matched by age, sex, and area of residence (urban versus rural) to population controls identified from the Manitoba Health Population Registry. Provincial pharmacy, hospital admissions, medical claims, and MCR data were used to determine infection, second malignancies, and IgR therapy. Immune dysfunction was defined as two or more infections, a diagnosis with a secondary malignancy, or receipt of IgR therapy. The pre-diagnosis time period was defined as three to 15 months prior to diagnosis. The pre-treatment time period was defined as 12 months prior to treatment. The following analyses were used: conditional logistic regression for objective 1, competing risk for objective 2, logistic regression for objective 3, and logistic GEE models for objective 4.

Results: A total of 1,776 CLL patients were matched to 17,760 non-CLL controls. Sixty-two percent were male, the mean age at diagnosis was 71 years, and 62% lived in an urban area. Fifty-one percent of CLL patients had a pre-diagnosis infection compared to 46% of controls. Compared to individuals with no prior infection, those who had a prior infection were more likely to be diagnosed with CLL (Odds Ratio (OR) 1.17, 95% confidence Interval (CI) 1.03, 1.33 for one infection, OR 1.29, 95% CI 1.15, 1.45 for two or more infections). After adjusting for the number of outpatient visits and comorbidity, individuals with two or more infections were 14% more likely to be diagnosed with CLL (OR 1.14, 95% CI 1.00-1.30).

Conclusions: We found that infections that occurred in the three to 15 months before diagnosis increased the odds of being diagnosed with CLL. Work is ongoing examining time to treatment, immune dysfunction by stage, as well comparing immune dysfunction before and after treatment.
CAR-T Cells for Systemic Lupus Erythematosus
Authors: Doglio Matteo , Ugolini Alessia , Bercher Clara , Toma Cristiano , Bonini Chiara , Ciceri Fabio , Camisa Barbara , Norata Rossana , Del Rosso Stefania , Sanvito Francesca , Casucci Monica , Manfredi Angelo
Published: December 2023

Systemic Lupus Erythematosus (SLE) is an autoimmune disease characterized by an abnormal inflammatory response against nuclear antigens with consequent tissue damage. Autoreactive B cells and auto-antibodies have a fundamental role in SLE pathogenesis. Lupus nephritis (LN) has a great impact on patients' survival and quality of life and still represents and unmet clinical need due to the lack of specific treatments and to the poor response to conventional immunosuppression. Regulatory T cells (Tregs) physiologically maintain the immune tolerance and are impaired in SLE. Polyclonal Treg transfer obtained unsatisfactory results due to the low number of disease-relevant antigen-specific cells. Chimeric Antigen Receptors (CARs) are molecules capable of redirecting T cell specificity. CAR-Tregs proved effective in pre-clinical mouse models of autoimmunity.

We aimed at developing a CAR-Treg based product to be employed in SLE in particular in LN.

We isolated Tregs from Healthy Donors Peripheral Blood Mononuclear Cells (PBMCs) and expanded them with IL-2 and rapamycin. We transduced Tregs with a Lentiviral Vector encoding for a second-generation anti-CD19 CAR, considering the relevant role of autoreactive B cells and autoantibodies in SLE. Engineered cells retained their immune suppressive capabilities upon polyclonal stimulation. Noticeably, they acquired new antigen-specific suppressive capacities, being able to block autologous B cell proliferation. We set up a humanized mouse model of SLE. In vivo, CAR-Tregs delayed the occurrence of B cell lymphopenia, producing immunomodulatory cytokines and without showing toxicity or reprogramming towards Th17 pro-inflammatory cells. In inflamed organs, CAR-Tregs restored the normal composition of the immune system.

In conclusion, we efficiently generated anti-CD19 CAR-Tregs and proved their efficacy both in vitro and in an in vivo humanized mouse model of lupus.
A Pilot Study to Determine the Safety and Efficacy of Repeated Hyperbaric Oxygen Therapy in Multiple Myeloma Patients Undergoing High-Dose Therapy and Autologous Stem/Progenitor Cell Transplantation
Authors: Huselton Eric J , Langstein Howard , Liesveld Jane L. , Aljitawi Omar
Published: December 2023

Background

Serum erythropoietin (EPO) negatively impacts hematopoietic stem cell homing and engraftment. Hyperbaric oxygen (HBO) therapy can reduce serum EPO in healthy volunteers and when given prior to stem cell infusion may improve engraftment after hematopoietic stem cell transplant (HSCT).

We previously performed a phase II trial randomizing patients with multiple myeloma undergoing high dose melphalan and autologous HSCT 1:1 between a single HBO treatment and no HBO. HBO was given as 100% oxygen, 2.5 ATA for a total of 90 min, in a single treatment on Day 0 prior to the transplant. A total of 99 patients were enrolled with 52 randomized to HBO. HBO significantly reduced EPO levels for the first 24 hours after auto transplant, but EPO levels quickly rebounded by 48 hours after transplant.

We hypothesized multiple HBO treatments will keep EPO levels low during the duration of stem cell homing (i.e: the first 72 hours after HSCT) and may improve neutrophil and NK cell recovery.

Methods

We performed a pilot study to evaluate the safety and tolerability of multiple HBO treatments during autologous HSCT. Patients with multiple myeloma undergoing autologous HSCT were eligible. Patients received HBO therapy, consisting of hyperbaric oxygen at 2.5 ATA for a total of 90 minutes breathing 100% oxygen on days 0 (prior to HSCT), 1, and 2 of transplant. The primary objective of this pilot study was to determine the safety of repeated HBO therapy in the setting, as defined by treatment limiting toxicity (TLT) including occurrence of seizure disorder, pneumothorax, death, or any irreversible grade Ill or any grade IV toxicity within 24 hours of HBO therapy. Secondary objectives were to determine the effects of multiple HBO therapy on neutrophil count recovery and the effect of multiple HBO on serum EPO.

Results

10 patients have been enrolled that are evaluable for the primary objective. All patients had multiple myeloma and 4 were female. 9/10 patients successfully completed all 3 HBO treatments and 1/10 completed HBO on days 1 and 2 only because of ear pain on day 0. No patients experienced treatment limiting toxicity. The median times to neutrophil and platelet engraftment was 12 days (range 11-14) and 16 days (range 14-28), respectively. The median length of hospitalization was 13 days (range 12-16). Febrile neutropenia occurred in 3/10 patients with just one incidence of documented infection. This was significantly less than the rate of febrile neutropenia in patients receiving a single treatment of HBO or no HBO (81% and 47%, respectively, p<0.05). 3 patients required red blood cell transfusion and 5 platelet transfusion.

Conclusions

Multiple HBO treatment were well tolerated without treatment limiting toxicity during autologous HSCT for multiple myeloma.
Predictors of unsustained measurable residual disease negativity in transplant-eligible patients with multiple myeloma
Authors: Guerrero Camila , Puig Noemi , Cedena María-Teresa , Calasanz María-José , Gutierrez Norma C. , Fernandez Manuela , Oriol Albert , Ríos-Tamayo Rafael , Hernandez Miguel-Teodoro , Martínez-Martínez Rafael , Bargay Joan , de Arriba Felipe , Palomera Luis , Gonzalez-Rodriguez Ana Pilar , Gonzalez Perez Marta-Sonia , Orfao Alberto , Mateos María-Victoria , Martinez-Lopez Joaquin , Rosiñol Laura , Bladé Joan , Lahuerta Juan-Jose , San-Miguel Jesus F. , Paiva Bruno
Published: December 2023

The role of measurable residual disease (MRD) negativity as a biomarker to stop treatment is being investigated in transplant-eligible patients with multiple myeloma (MM). Thus, it is important to identify risk factors of MRD resurgence and/or progressive disease (PD) among patients achieving undetectable MRD to avoid undertreating them. Here, we studied 267 newly diagnosed transplant-eligible patients with MM enrolled in the GEM2012MENOS65 and GEM2014MAIN clinical trials who achieved MRD negativity by next-generation flow cytometry. After a median follow-up of 73 months since the first MRD negative assessment, 111 of the 267 (42%) patients showed MRD resurgence and/or PD. The only prognostic factors at diagnosis that predicted MRD resurgence and/or PD were an International Staging System (ISS) 3 and the presence of ≥0.01% circulating tumor cells (CTCs). Failure to achieve MRD negativity after induction also predicted higher risk of MRD resurgence and/or PD. Patients having 0 vs 1 vs ≥2 risk factors (ISS 3, ≥0.01% CTCs, and late MRD negativity) showed 5-year rates of MRD resurgence and/or PD of 16%, 33%, and 57%, respectively (P < .001). Thus, these easily measurable risk factors could help refine the selection of patients for whom treatment cessation after MRD negativity is being investigated in clinical trials. This trial was registered at www.clinicaltrials.gov as NCT01916252 and NCT02406144.
Impaired O2 unloading from stored blood results in diffusion-limited O2 release at tissues: evidence from human kidneys
Authors: Dumbill Richard , Rabcuka Julija , Fallon John , Knight Simon , Hunter James , Voyce Daniel , Barrett Jacob , Ellen Matt , Weissenbacher Annemarie , Kurniawan Tetuko , Blonski Slawomir , Korczyk Piotr Michal , Ploeg Rutger , Coussios Constantin , Friend Peter , Swietach Pawel
Published: December 2023

The volume of oxygen drawn from systemic capillaries down a partial pressure gradient is determined by the oxygen content of red blood cells (RBCs) and their oxygen-unloading kinetics, although the latter is assumed to be rapid and, therefore, not a meaningful factor. Under this paradigm, oxygen transfer to tissues is perfusion-limited. Consequently, clinical treatments to optimize oxygen delivery aim at improving blood flow and arterial oxygen content, rather than RBC oxygen handling. Although the oxygen-carrying capacity of blood is increased with transfusion, studies have shown that stored blood undergoes kinetic attrition of oxygen release, which may compromise overall oxygen delivery to tissues by causing transport to become diffusion-limited. We sought evidence for diffusion-limited oxygen release in viable human kidneys, normothermically perfused with stored blood. In a cohort of kidneys that went on to be transplanted, renal respiration correlated inversely with the time-constant of oxygen unloading from RBCs used for perfusion. Furthermore, the renal respiratory rate did not correlate with arterial O2 delivery unless this factored the rate of oxygen-release from RBCs, as expected from diffusion-limited transport. To test for a rescue effect, perfusion of kidneys deemed unsuitable for transplantation was alternated between stored and rejuvenated RBCs of the same donation. This experiment controlled oxygen-unloading, without intervening ischemia, holding all non-RBC parameters constant. Rejuvenated oxygen-unloading kinetics improved the kidney’s oxygen diffusion capacity and increased cortical oxygen partial pressure by 60%. Thus, oxygen delivery to tissues can become diffusion-limited during perfusion with stored blood, which has implications in scenarios, such as ex vivo organ perfusion, major hemorrhage, and pediatric transfusion. This trial was registered at www.clinicaltrials.gov as #ISRCTN13292277.
Impact of population structure in the estimation of recent historical effective population size by the software GONE
Authors: Novo Irene , Ordás Pilar , Moraga Natalia , Santiago Enrique , Quesada Humberto , Caballero Armando
Published: December 2023

Background

Effective population size (Ne) is a crucial parameter in conservation genetics and animal breeding. A recent method, implemented by the software GONE, has been shown to be rather accurate in estimating recent historical changes in Ne from a single sample of individuals. However, GONE estimations assume that the population being studied has remained isolated for a period of time, that is, without migration or confluence of other populations. If this occurs, the estimates of Ne can be heavily biased. In this paper, we evaluate the impact of migration and admixture on the estimates of historical Ne provided by GONE through a series of computer simulations considering several scenarios: (a) the mixture of two or more ancestral populations; (b) subpopulations that continuously exchange individuals through migration; (c) populations receiving migrants from a large source; and (d) populations with balanced systems of chromosomal inversions, which also generate genetic structure.

Results

Our results indicate that the estimates of historical Ne provided by GONE may be substantially biased when there has been a recent mixture of populations that were previously separated for a long period of time. Similarly, biases may occur when the rate of continued migration between populations is low, or when chromosomal inversions are present at high frequencies. However, some biases due to population structuring can be eliminated by conducting population structure analyses and restricting the estimation to the differentiated groups. In addition, disregarding the genomic regions that are involved in inversions can also remove biases in the estimates of Ne.

Conclusions

Different kinds of deviations from isolation and panmixia of the populations can generate biases in the recent historical estimates of Ne. Therefore, estimation of past demography could benefit from performing population structure analyses beforehand, by mitigating the impact of these biases on historical Ne estimates.
A survey on the current status of Helicobacter pylori infection in households in Hainan Province, China
Authors: Liu Danni , Pan Jing , Chen Zhengyi , Li Sailian , Ma Jiamei , Xiao Yening , Wang Danhong , Mu Ganggang , Lin Ya , Li Juyuan , Chen Zhai , Huang Xiaoxi
Published: December 2023

Objective

This study aims to assess the prevalence of Helicobacter pylori (Hp) infection at the household level in Hainan Province in China and identify the factors that contribute to its spread. The findings of this study have significant implications for public health prevention strategies in the Hainan region.

Methods

A total of 421 families, comprising 1355 individuals, were tested for Hp infection across five cities in Hainan Province between July 2021 and April 2022. The study utilized questionnaires that included questions about personal characteristics, household shared lifestyle and dietary habits, and potential pathways of Hp infection in children to identify potential factors linked to household Hp infection and transmission patterns.

Results

The prevalence of Hp infection on an individual basis was 46.72% (629/1355), with age ≥ 20 years, being married and having junior secondary education and above as risk factors for Hp infection. The prevalence of Hp infection in households was 80.29% (338/421), household size of 5, 6 and above were risk factors for Hp infection with Odds Ratios (ORs) of 4.09 (1.17–14.33) and 15.19 (2.01–114.73), respectively, household income ≥ 100,000 yuan and drinking boiled water from a tap source were protective factors for Hp infection with ORs of 0.52 (0.31–0.89) and 0.51 (0.28–0.95), respectively. The prevalence of Hp infection among minors in the household was 24.89% (58/233), with paternal infection and maternal infection as risk factors for child infection, with ORs of 2.93 (1.29–6.62) and 2.51 (1.07–5.89), respectively.

Conclusion

Hp infection was prevalent among Hainan families, and interaction with infected family members may be the primary cause of transmission.
Effect of Helicobacter pylori eradication evaluated using magnifying endoscopy with narrow-band imaging in mixed-type early gastric Cancer
Authors: Tokai Yoshitaka , Horiuchi Yusuke , Yamamoto Noriko , Namikawa Ken , Yoshimizu Shoichi , Ishiyama Akiyoshi , Yoshio Toshiyuki , Hirasawa Toshiaki , Fujisaki Junko
Published: December 2023

Background

The effect of Helicobacter pylori (H.pylori) eradication therapy on mixed-histological-type gastric cancer remains unclear. This study aimed to clarify the effect of H. pylori eradication therapy on mixed-histological-type early gastric cancer using endoscopic and histological findings.

Methods

This single-center, retrospective study included patients with mixed-histological-type gastric cancer who underwent endoscopic submucosal dissection at the Cancer Institute Hospital. We compared detailed magnifying endoscopy with narrow-band imaging findings between eradicated and non-eradicated groups of patients with differentiated-type- and undifferentiated-type-predominant cancers. Subsequently, we performed histological evaluations of the non-cancerous epithelium covering differentiated-type components.

Results

A total of 124 patients with mixed-type early gastric cancer were enrolled (eradicated group: 62 differentiated-type-predominant cancer patients and 8 undifferentiated-type-predominant cancer patients; non-eradication group: 40 differentiated-type-predominant cancer patients and 14 undifferentiated-type-predominant cancer patients). Regarding differentiated-type-predominant cancer, differentiated-type findings were detected in all patients in eradicated and non-eradicated groups. The difference in the detection rate of undifferentiated-type findings between both groups was not significant in differentiated-type-predominant cancer patients. In differentiated-type-predominant cancers, the percentage of non-cancerous epithelium covering differentiated-type components was higher in the eradicated group than in the non-eradicated group (median: 60% vs. 40%, p < 0.001).

Conclusions

Although the pathological findings of differentiated-type-predominant cancer were affected by H. pylori eradication, eradication did not affect the diagnosis of differentiated-type-predominant early gastric cancer using magnifying endoscopy with narrow-band imaging. ME-NBI is useful for the early detection of D-MIX EGCs and diagnosis of histological types during endoscopy, regardless of whether H. pylori eradication therapy has been administered.
Paranasal sinus angiosarcoma with facial paralysis as a novel manifestation: a case report and literature review
Authors: Chai Chengcheng , Feng Xiaocong , Li Kai , Yan Zhaoxian , Tan Shuyi , Weng Jin , Huang Fan , Huang Jianpeng , Zhu Xinru , Zhuo Xuehui , Chen Hai
Published: December 2023

Background

Paranasal sinus angiosarcoma is an uncommon malignancy, with only a few reported cases worldwide. Although it exhibits multiple symptoms, facial paralysis has not been previously documented as a noticeable presentation.

Case Presentation

In this case, we report a 40-year-old male who presented with facial numbness and pain for one month, weakness of his facial muscles for 15 days, and recurrent right epistaxis for 1 year. He had a history of nasal inflammatory polyps with chronic sinusitis. Computed tomography and magnetic resonance imaging showed space-occupying lesions in the right nasal cavity and maxillary sinus, with bone destruction occurring in the sinus wall and turbinate. This patient then underwent endoscopic surgery. According to the histopathological and immunohistochemical results, he was eventually diagnosed with paranasal sinus angiosarcoma in April 2021. To date, this patient has not initiated any radiotherapy or chemotherapy and has survived with lymphatic metastasis for at least 3 years.

Conclusions

This manuscript suggests that paranasal sinus angiosarcoma can present with facial paralysis. Moreover, pathological and immunohistochemical tests are still vital for diagnosing paranasal sinus angiosarcoma and differential diagnosis. Additionally, regular follow-up is crucial for patients with paranasal sinus angiosarcoma, enabling monitoring of recurrence, metastasis, and recovery while contributing valuable clinical data to understanding this rare disease and associated research endeavours.
The global prevalence of low back pain in pregnancy: a comprehensive systematic review and meta-analysis
Authors: Salari Nader , Mohammadi Aida , Hemmati Mahvan , Hasheminezhad Razie , Kani Salim , Shohaimi Shamarina , Mohammadi Masoud
Published: December 2023

Background

Back pain during pregnancy is often considered as an unavoidable problem and can reduce the quality of life or disability of pregnant women. The aim of this study is to determine the global prevalence of back pain in pregnancy based on a systematic review and meta-analysis.

Methods

In this study, Researchers systematically searched electronic databases PubMed, Scopus, Web of Science, Embase, ScienceDirect, and Google Scholar search engines for studies until September 2023. To analyze data, the random effects model was used, and the heterogeneity of the studies was checked with the I2 index. Data analysis was performed by software (Version 2 Comprehensive Meta-Analysis).

Results

In the review of 28 studies with a sample size of 12,908 people, the I2 heterogeneity test showed high heterogeneity (I2: 98.4). Based on this, the random effects method was used to analyze the results. Therefore, the meta-analysis reported the global prevalence of back pain at 40.5 (95% CI: 33–48.4) during pregnancy. Also, according to the meta-analysis, the global prevalence of back pain in the first trimester of pregnancy is 28.3 (95%CI: 10.5–57.1), in the second trimester is 36.8 (95%CI: 30.4–43.7) and in the third trimester of pregnancy was reported as 47.8 (95% CI: 37.2–58.6).

Conclusion

In this meta-analysis, the overall prevalence of back pain in pregnant women was reported to be significant, so it is necessary for health policymakers to pay more attention to complications during pregnancy, in addition to increasing society's awareness of pregnant mothers, with timely diagnosis and treatment of such disorders, it can lead to improvement; and reduction in Complications caused by pregnancy and becoming more pleasant during pregnancy.
Determinants of mortality among pediatric patients admitted to Wolaita Sodo University Comprehensive Specialized Hospital with acute bacterial meningitis, Southern Ethiopia: an unmatched case–control study
Authors: Borko Ushula Deboch , Gelgelu Temesgen Bati , Zema Zewde , Alemu Afework , Dendir Getahun , Israel Eskinder , Abiso Temesgen Lera , Woldegeorgis Beshada Zerfu
Published: December 2023

Background

People of all ages suffer from acute bacterial meningitis, but children are the most vulnerable, accounting for over 50% of all cases and deaths in children under the age of five. It is the leading cause of morbidity, mortality, and long-term suffering worldwide. Children are at great risk of disease and mortality due to a lack of specific immunity associated with their young age. As a result, determinants of death were found among pediatric patients treated with acute bacterial meningitis at Wolaita Sodo University Comprehensive Specialized Hospital in Southern Ethiopia.

Methods

A facility-based unmatched case–control study was conducted on pediatric patients admitted with acute bacterial meningitis at Wolaita Sodo University Comprehensive Specialized Hospital from July 1, 2019, to June 30, 2022. A total of 355 (71 cases and 284 controls) pediatric medical charts were used for data extraction using a preestablished checklist. Data were checked for completeness and consistency, entered into Epi-Data version 4.6 software, and transported to SPSS version 25 for analysis. Multivariable logistic regression analysis was performed to identify the independent determinants of acute bacterial meningitis mortality at a P value of < 0.05 along with a 95% confidence interval (CI).

Results

Age between 2 months and 5 years (adjusted odds ratio (AOR) = 3.19, 95% CI = 1.15–8.88), admission in the summer season (AOR = 0.27, 95% CI = 0.15–0.49), and family size greater than or equal to six (AOR = 3.13, 95% CI = 1.76–5.56), initial antibiotic change (AOR = 10.81, 95% CI = 2.10–55.7), clinical features at presentation such as loss of consciousness (AOR = 16.90, 95% CI = 4.70–60.4), abnormal body movements (seizures) (AOR = 6.51, 95% CI = 1.82–23.4), increased intracranial pressure (AOR = 3.63, 95% CI = 1.78–7.4), malnutrition (AOR = 2.98, 95% CI = 1.34–6.59) and presence of more than one comorbidity (AOR = 3.03, 95% CI = 1.03–9.03) were found to be determinants of acute bacterial meningitis mortality.

Conclusions

In summary, children aged 2 months to 5 years from large families ( > = 6) with a history of initial antibiotic change, malnutrition, more than one comorbidity, and worse clinical characteristics were related to greater death due to acute bacterial mortality in this study.
Protocol for a randomised controlled trial of a healthy relationship tool for men who use intimate partner violence (BETTER MAN)
Authors: Hegarty Kelsey , Tarzia Laura , Navarro Medel Carolina , Hameed Mohajer , Chondros Patty , Gold Lisa , Tassone Simone , Feder Gene , Humphreys Cathy
Published: December 2023

Background

Intimate partner violence (IPV) is common globally, but there is a lack of research on how to intervene early with men who might be using IPV. Building on evidence supporting the benefits of online interventions for women victim/survivors, this study aims to test whether a healthy relationship website (BETTER MAN) is effective at improving men’s help seeking, their recognition of behaviours as IPV and their readiness to change their behaviours.

Methods/design

In this two-group, pragmatic randomised controlled trial, men aged 18–50 years residing in Australia who have been in an adult intimate relationship (female, male or non-binary partner) in the past 12 months are eligible. Men who report being worried about their behaviour or have had others express concerns about their behaviour towards a partner in the past 12 months will be randomised with a 1:1 allocation ratio to receive the BETTER MAN website or a comparator website (basic healthy relationships information). The BETTER MAN intervention includes self-directed, interactive reflection activities spread across three modules: Better Relationships, Better Values and Better Communication, with a final “action plan” of strategies and resources. Using an intention to treat approach, the primary analysis will estimate between-group difference in the proportion of men who report undertaking help-seeking behaviours for relationship issues in the last 6 months, at 6 months post-baseline. Analysis of secondary outcomes will estimate between-group differences in: (i) mean score of awareness of behaviours in relationships as abusive immediately post-use of website; (ii) mean score on readiness to change immediately post-use of website and 3 months after baseline; and (iii) cost-effectiveness.

Discussion

This trial will evaluate the effectiveness of an online healthy relationship tool for men who may use IPV. BETTER MAN could be incorporated into practice in community and health settings, providing an evidence-informed website to assist men to seek help to promote healthy relationships and reduce use of IPV.

Trial registration

ACTRN12622000786796 with the Australian New Zealand Clinical Trials Registry: 2 June 2022.

Version: 1 (28 September 2023).
Motives for leisure-time physical activity participation: an analysis of their prevalence, consistency and associations with activity type and social background
Authors: Elmose-Østerlund Karsten , Dalgas Birgitte Westerskov , Bredahl Thomas Viskum Gjelstrup , Lenze Lars , Høyer-Kruse Jens , Ibsen Bjarne
Published: December 2023

Background

Studies argue that knowledge about motives for physical activity participation can inform activities, initiatives and interventions to promote physical activity. However, most of these studies are based on small sample sizes and only include participants within a few selected types of PA. Further, they have not examined the consistency of individuals’ motives across different activity types. As a result, this article examines RQ1: the most prevalent motives, RQ2: the association of motives with activity type and social background characteristics, and RQ3: the consistency of motives across different activity types.

Methods

We utilised data from a survey of physical activity participation among 163,000 adult Danes (aged 15 + years). In the survey, the participants were asked about their participation in thirteen activity types and about their motives for practising the activity types they reported to do at least weekly. The motive items were operationalised based on the eight dimensions in the Physical Activity and Leisure Motivation Scale (PALMS). We conducted analyses of mean values and standard deviations as well as multilevel regression analyses.

Results

We identified large differences in the importance of different motives for physical activity participation. The three most important motives were psychological condition (M = 4.54), physical condition (M = 4.48) and enjoyment (M = 4.36). We also found significant associations between motives and activity types in particular, but also between motives and social background characteristics (gender, age and educational level). For instance, we found that compared to running, physical condition was a much less important motive in outdoor activities (b = -3.01), activities on water (b = -2.44) and street sports (b = -2.38). Finally, our analysis showed how individuals’ motives are not consistent across different activity types.

Conclusions

Our study contributes to the literature on motives for physical activity participation by using a large sample of individuals and by differentiating motives according to a wide range of activity types. The results underline the need to study motives in relation to activity types, as there are large differences in the prevalence of different motives. Our findings suggest that motives are not consistent across activity types, but rather they develop in an interplay between the individual and the activity type practised.
Environmental quality and its impact on total fertility rate: an econometric analysis from a new perspective
Authors: Haq Shah Md Atiqul , Chowdhury Mohammad Ashraful Ferdous , Ahmed Khandaker Jafor , Chowdhury Mohammed Thanvir Ahmed
Published: December 2023

Background

Environmental quality significantly affects various aspects of human existence. This study employs ecological footprint as a proxy to assess the impact of environmental quality on the TFR, measured as births per woman. This study investigates the extent to which ecological footprint indicators impact on the TFR in across 31 countries between from 1990 to 2017.

Methods

We gathered data on ecological footprints, specifically carbon, agricultural land, grazing land, forest products, and fisheries, from the Global Footprint Network. Information on the TFR, Human Development Index (HDI), and per capita Gross National Income (GNI) were sourced from the World Bank and the United Nations. We applied static panel and quantile regression models to scrutinize the connection between the ecological footprint and TFR, showing how the former influences the latter.

Results

The outcomes reveal that, in both fixed and random effects models, factors including HDI, carbon, and fishing grounds exert a negative influence on TFR, all at a significance level of p < 0.01. Conversely, cropland and forest product footprints exhibited a favorable impact on the TFR (p < 0.01). Furthermore, GNI per capita positively affected the TFR in both models, with a p-value of 0.01. Quantiles regression analysis demonstrated that HDI and carbon footprint had a negative impact on TFR across all quantiles. This statistical significance is maintained for all quantiles, although it is only significant for the carbon footprint up to the 60th quantile, at p < 0.01.

Conclusions

This study establishes a negative correlation between specific ecological footprint indicators, such as carbon and fishing grounds, and TFR. Conversely, there was a positive correlation between the footprint of forest products and the TFR. The primary conclusion drawn is that there is heterogeneity in the results regarding the relationship between ecological footprint and TFR. Moreover, the ecological footprint indicators considered in this study did not uniformly influence TFR. Each ecological footprint indicator exhibited distinct effects on the TFR, displaying either positive or negative correlation coefficients. Future research endeavors may delve into how ecological footprints impact other population dynamics, such as mortality and migration.