bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combinatorial genome engineering strategy for CAR-Treg antigen-specific immune protection of stem cell-derived cells
Authors: Barra Jessie , Robino Rob , Castro-Gutierrez Roberto , Ferreira Leonardo , Russ Holger 
Published: November 2024

Abstract
Improved methods for generating human pluripotent stem cell (hPSC)-derived cells and tissues have rapidly expanded the field of regenerative medicine. Yet, in most cases, hPSC-derived cells need to be protected, ideally in a localized manner, from an antagonistic host immune response. Chimeric antigen receptor (CAR) technology can confer new antigen specificities to effector T cells and, more recently, regulatory T cells (Tregs), potent immunosuppressive cells. However, one challenge in CAR design is identifying a target molecule uniquely expressed by the cells of interest to prevent unwanted off-target effects. Here, we developed a combinatorial genetic engineering approach to confer CAR-Treg-mediated localized immune protection specifically to transplanted stem cell-derived cells using a humanized type 1 diabetes preclinical mouse model. We engineered hPSCs to express a truncated epidermal growth factor receptor (EGFRt) and differentiated functional stem cell derived beta-like cells (sBCs) from them. In parallel, we generated EGFR CAR-Tregs that were activated by EGFRt-expressing sBCs without disrupting Treg identity. Strikingly, activated CAR-Tregs suppressed innate and adaptive effector immune responses in vitro and prevented effector CAR-T-cell-mediated sBC graft destruction in vivo. These data provide evidence that combinatorial genome engineering of hPSCs and Tregs can be harnessed to protect hPSC-derived tissues from immune attack via immune tolerance induction.
Notch2+ Marginal zone B cell depletion decreases antigen shuttle to Follicular Dendritic cells and reduces alloantibody production
Authors: Benedetti Gassen Rodrigo , de Jesus Borges Thiago , Magee Ciara , Murakami Naoka , Riella Leonardo 
Published: November 2024

Abstract
Chronic antibody-mediated rejection (CAMR) is a major cause of allograft loss. Most anti-rejection therapies target T cells and novel treatments to suppress CAMR are needed. Notch2+ Marginal zone (MZ) B cells have a key role in rapidly generating antibodies and facilitating the shuttle of antigens to follicular dendritic cells (FDCs). The FDC:B cell interaction is crucial to the formation of memory B cells and long-lived plasma cells. To evaluate the role of Notch2+ MZ B cells in transplantation, we utilize a mouse model of kidney transplantation, in which HLA-A2-expressing allografts are transplanted into B6 recipients. Here, we demonstrate that the anti-Notch2 treatment depletes MZ B cells and decreases pathological features of alloantibody-mediated rejection. Mechanistically, the anti-Notch2 treatment decreases plasma cells and the formation of donor-specific antibodies abrogates C4d deposition and reduces graft-infiltrating NK cells. Moreover, the Notch2+ MZ B cell depletion decreases the shuttling of antigens to FDCs as evidenced by the reduction of antigen (HLA.A2+) within FDCs (CD35+) clusters. Thus, Notch2+ MZ B cell depletion reduces alloantibody responses by decreasing alloantigen shutting to FDCs, leading to fewer signs of antibody-mediated graft rejection. Further elucidating the role of the Notch2 pathway will be important to the development of novel therapeutic strategies to prevent alloantibody production.
Activated B cell transcriptome induced by mATG treatment of heart allograft recipients
Authors: Yamamoto Yosuke , Anna Valujskikh , Gorbacheva Victoria , Fan Ran , Nicosia Michael , Fairchild Robert , Gaudette Brian 
Published: November 2024

Abstract
After transplant recipient treatment with anti-thymocyte globulin (ATG), B cells recover and drive reconstitution of depletion-resistant memory T cells. This study investigated the effects of ATG depletion on B cells in transplant recipients. Experimental groups were: 1) BALB/c to B6 heart Tx; 2) heart Tx + ATG; 3) ATG alone; 4) naïve B6. Spleen cells were isolated on d. 8 posttransplant and analyzed by single cell RNA-seq. Across all B cell subsets, immune stimulatory genes including lymphotoxin A and B, MHC-related and costimulatory genes were increased in Heart Tx + ATG group. Despite T cell depletion, recipients of heart Tx + ATG had twice as many germinal center (GC) B cells with increased expression of MHC II-associated and costimulatory genes as other groups and uniquely showed signs of early IgG class switching in GC and plasma cells. Heart Tx + ATG treatment induced a robust interferon response signature across B cell subsets, quite strikingly in the marginal zone (MZ) and transitional B cells. Targeting MZ B cells with anti-integrin mAb or the use MZ B cell-deficient recipients delayed recovery of CD8 T lymphocytes compared to controls suggesting that interferon signaling in MZ B cells is driving their proinflammatory functions required for T cell reconstitution. In sum, ATG lymphoablation induce proinflammatory signature in recipient B cells consistent with their role in T cell homeostatic expansion and raising a possibility of enhanced humoral responses.
Coronavirus Immune History Affects Breadth of Anti-SARS-CoV-2 Receptor-Binding Domain Responses.
Authors: Brice David , Lin Chun-Yang , Castellaw Ashley , Allen E , Wehenkel Marie , Lewis Carlessia , Roubidoux Ericka , Wolf Joshua , Thomas Paul , Schultz-Cherry Stacey , Webby Richard , McGargill Maureen 
Published: November 2024

Abstract
As novel SARS-CoV-2 variants continue to emerge, it is essential to gain further insight into the impact of imprinting on the protective antibody response to SARS-CoV-2. Utilizing a longitudinal cohort with samples collected before and after infection or vaccination, we assessed associations between pre-existing humoral immunity to common cold human coronaviruses (hCoVs) and the subsequent antibody response to the Spike Receptor Binding Domain (RBD) of different variants of SARS-CoV-2 following infection and vaccination. We found baseline anti-hCoV Spike IgM levels negatively correlate with anti-RBD breadth after infection, but not vaccination, with binding to the RBDs more antigenically distant to the Wuhan strain most affected. To investigate the effect of prior exposure to Spike proteins of individual coronaviruses, we utilized a mouse model. Unexpectedly, initial vaccination with SARS-CoV-1 Spike generated higher levels of SARS-CoV-2 RBD-specific antibodies compared to initial immunization with SARS-CoV-2 Spike, a phenomenon that continued even after SARS-CoV-2 Spike boosting of both groups. Moreover, SARS-CoV-1 Spike vaccination induced a broader and more durable SARS-CoV-2 RBD antibody response compared to SARS-CoV-2 Spike vaccination. Overall, these data highlight the lasting impact of prior exposure to related coronaviruses and demonstrate how SARS-CoV-1 Spike exposure induces a broader antibody response to the RBD of SARS-CoV-2 variants compared to SARS-CoV-2 Spike.
Characterization of AMEV2, A Multi-Peptide Vaccine Against Acinetobacter baumannii
Authors: Jeffreys Sean , Yu Jieh-Juen , Tompkins Megan , Aki Jadelynn , Guentzel Neal , Chambers James , Hung Chiung-Yu , Arulanandam Bernard 
Published: November 2024

Abstract
Multi-drug resistant (MDR) Acinetobacter baumannii is an opportunistic pathogen associated with hospital-acquired infections. This pathogen’s extensive MDR phenotype offers limited treatment options and requires alternative immunotherapeutic interventions, such as prophylactic vaccination in susceptible populations. In this study, we employed immunoinformatics to identify peptides containing both putative B and T cell epitopes from proteins associated with A. baumannii pathogenesis. An Acinetobacter Multi-Epitope Vaccine (AMEV2) comprising an A. baumannii thioredoxin A leading protein sequence followed by 5 identified peptide antigens was created. Subcutaneous immunization of mice with AMEV2 plus AddaS03 adjuvant demonstrates robust humoral and cellular immunogenicity. AMEV2 immunization results in high antibody titers to the antigen and the constitutional peptide components in addition to high frequencies of antibody-secreting cells in the spleen and bone marrow of the mice. In vitro opsonophagocytosis assays demonstrate anti-AMEV2 serum enhances the killing of opsonized bacteria by bone marrow-derived macrophages. Additionally, AMEV2 immunized mice were protected from both a lethal intraperitoneal and intranasal challenge with hypervirulent strains of A. baumannii, 4 weeks post-final vaccination, and achieved survival rates of 80% and 60%, respectively. AMEV2 vaccination affords antibody-mediated protection against hypervirulent A. baumannii infections.
Risk factors for hepatocellular carcinoma in cirrhosis: A comprehensive analysis from a decade-long study
Authors: Zhou Da-Qiong , Liu Jiang-Yu , Zhao Feng , Zhang Jing , Liu Li-Li , Jia Jian-Ru , Cao Zhen-Huan 
Published: November 2024

BACKGROUND
Cirrhosis is a significant risk factor for the development of hepatocellular carcinoma (HCC). Variability in HCC risk among patients with cirrhosis is notable, particularly when considering the diverse etiologies of cirrhosis.
AIM
To identify specific risk factors contributing to HCC development in patients with cirrhosis.
METHODS
This retrospective study analyzed data from cirrhotic patients at Beijing Youan Hospital from January 1, 2012 to September 30, 2022 with at least 6 mo of follow-up. Patient demographics, medical histories, etiologies, and clinical characteristics were examined. Cox regression analysis was used to analyze correlations of the above parameters with hepatocarcinogenesis, while competing risk regression was used to estimate their adjusted hazard ratios accounting for death. The cumulative incidence was plotted over time.
RESULTS
Overall, 5417 patients with cirrhosis (median age: 54 years; 65.8% males) were analyzed. Hepatitis B virus (HBV) was the most common etiology (23.3%), with 25% (n = 1352) developing HCC over a 2.9-year follow-up period. Patients with multiple etiologies had the HCC highest incidence (30.3%), followed by those with HBV-related cirrhosis (29.5%). Significant risk factors included male sex, advanced age, hepatitis C virus (HCV) infection, elevated blood ammonia, and low platelet count. Men had a higher 5-year HCC risk than women (37.0% vs 31.5%). HBV, HCV, and HBV/HCV co-infected patients had 5-year risks of HCC of 45.8%, 42.9%, and 48.1%, respectively, compared to 29.5% in nonviral hepatitis cases, highlighting the significant HCC risk from viral hepatitis, especially HBV, and underscores the importance of monitoring these high-risk groups.
CONCLUSION
In conclusion, HBV-related cirrhosis strongly correlates with HCC, with male sex, older age, viral hepatitis, elevated blood ammonia, and lower albumin and platelet levels increasing the risk of HCC.
Vitamin D 1,25-Dihydroxyvitamin D3 reduces lipid accumulation in hepatocytes by inhibiting M1 macrophage polarization
Authors: Luo Wen-Jing , Dong Xian-Wen , Ye Hua , Zhao Qiao-Su , Zhang Qiu-Bo , Guo Wen-Ying , Liu Hui-Wei , Xu Feng 
Published: November 2024

BACKGROUND
Non-alcoholic fatty liver disease (NAFLD), which is a significant liver condition associated with metabolic syndrome, is the leading cause of liver diseases globally and its prevalence is on the rise in most nations. The protective impact of vitamin D on NAFLD and its specific mechanism remains unclear.
AIM
To examine the role of vitamin D in NAFLD and how vitamin D affects the polarization of hepatic macrophages in NAFLD through the vitamin D receptor (VDR)-peroxisome proliferator activated receptor (PPAR)γ pathway.
METHODS
Wild-type C57BL/6 mice were provided with a high-fat diet to trigger NAFLD model and administered 1,25-dihydroxy-vitamin D [1,25(OH)2D3] supplementation. 1,25(OH)2D3 was given to RAW264.7 macrophages that had been treated with lipid, and a co-culture with AML12 hepatocytes was set up. Lipid accumulation, lipid metabolism enzymes, M1/M2 phenotype markers, proinflammatory cytokines and VDR-PPARγ pathway were determined.
RESULTS
Supplementation with 1,25(OH)2D3 relieved hepatic steatosis and decreased the proinflammatory M1 polarization of hepatic macrophages in NAFLD. Administration of 1,25(OH)2D3 suppressed the proinflammatory M1 polarization of macrophages induced by fatty acids, thereby directly relieving lipid accumulation and metabolism in hepatocytes. The VDR-PPARγ pathway had a notable impact on reversing lipid-induced proinflammatory M1 polarization of macrophages regulated by the administration of 1,25(OH)2D3.
CONCLUSION
Supplementation with 1,25(OH)2D3 improved hepatic steatosis and lipid metabolism in NAFLD, linked to its capacity to reverse the proinflammatory M1 polarization of hepatic macrophages, partially by regulating the VDR-PPARγ pathway. The involvement of 1,25(OH)2D3 in inhibiting fatty-acid-induced proinflammatory M1 polarization of macrophages played a direct role in relieving lipid accumulation and metabolism in hepatocytes.
Farmer’s willingness to adopt bamboo (<i>Bambusa vulgaris</i>) in agroforestry along selected areas in Ido Local Government Area, Oyo State, Nigeria
Authors: Okanlawon F.B. , Olaoye K.O. , Badmus M.O. , Ogunbamowo P.O. , Areo O.S. , Adelusi F.T. 
Published: November 2024

This study was carried out to investigate the adoption of Bambusa vulgaris in agro-forestry practices along some selected farms in Ido Local Government Area of Ibadan, Oyo State, Nigeria. A simple random sampling method was used, while 50 pieces of semi-structured interview schedule were randomly administered among agro-forestry farmers in the local government area. The data collected was analysed using SPSS version 20 and was presented using Tables, Pie charts, and Bar charts. The results indicate that farming practices in the study area are predominantly male-dominated (90.0%) and at their prime and active age (86.0%) with little or no formal education (54.0%) coupled with marital responsibility (100.0%). The majority (86.0%) of the access to land ownership for the agro- forestry farmers was mostly communal and owned showing family attributes still exist. The regular farming method adopted there is basically to feed their family (60.0%) and to generate income from sale of products (40.0%) and this has been on for between 0-21 years but their willingness to adopt agro-forestry was observed (100.0%), while citing access to fertilizer was seen as a major problem. But adoption of agro-forestry farming was made to be seen as a means in this study as indicative of soil fertility. There is an indication that most of the farmers (83.0%) have either planted Bamboo before or seen people use it for several other purposes apart from agroforestry hence the adoption of Bamboo for agroforestry farming must be given an urgent attention so as to provide income and ecological stability.
Levels of evidence of therapeutic studies published in the East African Orthopaedic Journal
Authors: Lakati K.C. , Wambugu T.B.W. , Kiraga L.S. 
Published: November 2024

Background: The East African Orthopaedic Journal has published clinical scientific papers since 2007.
Objective: This study aimed to assess the levels of evidence of therapeutic studies published in the journal by using the Journal of Bone and Joint Surgery-American (JBJS-Am) level-of-evidence rating system.
Methods: All clinical therapeutic studies published in the journal from 2007 to 2023 were reviewed. Historical notes, editorials, cadaveric studies, case reports and literature reviews were excluded. Therapeutic studies were rated according to the JBJS-Am Level of Evidence (LOE) grading system as Level I, II, III, IV, or V.
Results: A total of 218 original studies were published in the journal, out of which 65 were therapeutic studies, representing 30% of the published papers. Level IV studies were the most predominant representing 69% of the therapeutic studies and 21% of the studies published. Level II studies represented 20% of the therapeutic studies and 6% of studies published. Levels 1 and III studies were the least predominant, both accounting for 5% and 6% respectively of the therapeutic studies and 1.4% and 1.8% of all the studies respectively. Level IV studies predominated over the years with little improvement in Level I, II and III studies.
Conclusion: Most studies published in the East African Orthopaedic Journal are Level IV studies. There has been no significant increase in Level I and II studies since inception of the journal.
Arable Crop Farmers’ Use of Private Extension Services in Ondo State, Nigeria
Authors: Ayodele Omowunmi Veronica , Akomolafe Samuel Kolawole 
Published: November 2024

The study assessed the arable crop farmers’ use of private extension services in Ondo State, Nigeria. A multi-stage sampling procedure was used in selecting 95 respondents in the study area and data were collected through an interview schedule. Data analysis was carried out using percentages and mean statistics. The study revealed there were few private extension service providers, and most (44.2%) of the arable crop farmers did not use private extension services. It also revealed that the respondents had an unfavourable attitude toward private extension services with a grand mean of 2.82. It was further revealed that only a few private extension providers were available to arable crop farmers. The farmers also believed that private extension could not provide all the services required for their agricultural production. The main constraint to private extension was that services of private extension were often geared to meeting the providers’ organizational needs (. The study concluded that farmers had unfavourable attitude to private extension. The study recommended a pluralistic approach to extension services and increased awareness to enlighten farmers about the importance of private extension services.
Economic Effects of COVID-19 Agricultural Loan Palliative on Poultry and Fish Farmers’ Production in Ondo State, Nigeria
Authors: Ayeni Adetoun , Okunlola James. O 
Published: November 2024

This study examined the effects of the COVID-19 Agricultural palliative loan on poultry and fish production in Ondo State Nigeria. The study specifically ascertained the socio-economic characteristics of the beneficiary farmers and determined the effect of the COVID-19 palliative loan on the farmers’ income level. A systematic sampling procedure was used in selecting 100 respondents for the study. Data were analyzed using frequency, percentage, bar charts, chi-square, T-Test and mean statistics. Findings revealed that 72% and 70% of fish and poultry farmers respectively were within the age group of 40-59 with a mean age of 51 years. Results also revealed that there was a 28.7% increment in the income of the fish farmers while poultry farmers received a 5.5% increment. There was no significant difference in the income of the fish farmers (t=-1.25) and poultry farmers (t=-1.24). It was recommended that there should be the creation of a loan monitoring and evaluation committee to provide continuous follow-up and technical support to future beneficiaries of such loans to ensure that they use the loan for the intended purpose.
holistic categorisation of address purposes as an analytical entry point to finding solutions for addressing governance in South Africa
Authors: Laldaparsad Sharthi , Coetzee Serena , Davis Nerhene 
Published: November 2024

An address is structured information allowing one to locate a building or other feature in the physical world; yet, in large parts of the world, including South Africa, many people must get by without such a utility. Although addresses are being rolled out, there is still no clarity concerning stakeholder responsibilities in the governance of addresses and address data in South Africa. In this paper, we present a categorisation of address purposes based on a holistic analysis of the many purposes of an address found in literature. Supported by this categorisation, stakeholders who could or should be involved in addressing governance in South Africa are identified. This first hierarchical categorisation of address purposes can be extended with additional levels of categorisation of new and diverse uses and purposes of addresses as they emerge. The categorisation confirms the significant value of addresses to society, governance, and the economy, sanctioning the need for investments for implementing an effective addressing infrastructure. The study serves as the analytical entry point to finding solutions for more coherent policy formulation and governance.
Mapping smallholder maize farm distribution using multi-temporal Sentinel-1 data integrated with Sentinel-2, DEM and CHIRPS precipitation data in Google Earth Engine
Authors: De Villiers Colette , Munghemezulu Cilence , Tesfamichael Solomon G. , Mashaba-Munghemezulu Zinhle , Chirima George J. 
Published: November 2024

Mapping smallholder maize farms in complex and uneven rural terrain is a major barrier to accurately documenting the spatial representation of the farming units. Remote sensing technologies rely on various satellite products for differentiating maize cropland cover from other land cover types. The potential for multi-temporal Sentinel-1 synthetic aperture radar (SAR), Sentinel-2, digital elevation model (DEM) and precipitation data obtained from Climate Hazards Group InfraRed Precipitation with Station data (CHIRPS) version 2.0 was investigated for mapping maize crop distributions during the growing seasons, 2015–2021, in the Sekhukhune municipal area of Limpopo, a province in South Africa. Sentinel-1 variables, including monthly VH, VV, VV+VH (V = vertical, H = horizontal) polarization band data and data issuing from the principal component analysis of VH polarization were integrated with Sentinel-2-derived normalized difference vegetation index (NDVI), DEM terrain, and precipitation data. The random forest (RF) algorithm was applied to distinguish maize crops from four other land cover types, including bare soil, natural vegetation, built-up area, and water. The findings indicated that the models that used only Sentinel-1 data as input data had overall accuracies below 71%. The best performing models producing overall accuracies above 83% for 2015–2021 were those where Sentinel-1 (VV+VH) data were integrated with all the ancillary data. Overall, the McNemar test indicated enhanced performance for models where all other ancillary input data had been incorporated. The results of our study show considerable temporal variation in maize area estimates, with 59 240.84 ha in the 2018/2019 growing season compared to 18 462.51 ha in the 2020/2021 growing season. The spatial information gathered through these models proved to be valuable and is essential for addressing food security, one of the objectives of the Sustainable Development Goals.