bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3 Efficacy of Foscarnet in Preventing HHV6 Encephalitis in Adult Single Cord Blood Transplantation
Authors: Suzuki Kotaro , Kanda Junya , Iemura Tomoki , Arai Yasuyuki , Watanabe Mizuki , Shimazu Yutaka , Kitawaki Toshio , Mizumoto Chisaki , Yamashita Kouhei , Takaori-Kondo Akifumi 
Published: September 2023

Abstract

Introduction
The risk of HHV-6 encephalitis is high in cord blood transplantation (CBT) and the prognosis after encephalitis is poor, but there is no clarity regarding effective prevention methods for HHV-6 encephalitis.

Objectives
We retrospectively evaluated the effect of foscarnet (FCN) in preventing HHV-6 encephalitis in CBT.

Methods
We included 184 patients who underwent single CBT at Kyoto University Hospital from 2005 to 2022. For those who developed HHV-6 encephalitis, we calculated cumulative steroid doses from transplantation to the date of encephalitis onset, and for those who did not develop encephalitis, we calculated them to 25 days (the median encephalitis onset).

Results
Median (range) age was 49 years (18-70 years); 82% used tacrolimus and MMF for GVHD prophylaxis; FCN was used prophylactically or preemptively in 141 patients (77%) to prevent HHV6 encephalitis. FCN was used in 35% of patients from day 7 post-transplant, 20% from the time of HHV-6 reactivation, and 8% after the start of steroid administration. HHV-6 encephalitis occurred in 18 (10%) of 184 patients.
The median cumulative steroid dose for those receiving steroids was 4.0 mg/kg. Steroid dose (mg/kg) had a significant effect on the development of encephalitis (HR 1.09, P=0.003); pre-engraftment immune reaction had no significant effect. The ROC curve showed that the cutoff for cumulative steroid dose that best predicted the development of encephalitis was 6.5 mg/kg. FCN prophylaxis showed no significant effect in preventing HHV6 encephalitis in the high-steroid group. However, FCN prophylaxis reduced the incidence of HHV6 encephalitis in the low-steroid group with marginal significance (HR 0.22, P=0.070). Patients who developed encephalitis without HHV6 prophylaxis had a significantly lower survival rate than those who did not develop encephalitis (1yr-OS, 25% vs. 69%). However, those who developed encephalitis during HHV6 prophylaxis did not differ significantly from those who did not develop encephalitis (1yr-OS, 59% vs. 69%) (Figure).

Discussion
FCN prophylaxis significantly reduced the incidence of encephalitis in the low-dose steroid group, whereas prophylaxis was not effective in the high-dose steroid group. However, prophylactic administration may improve the prognosis after the onset of encephalitis.
Abstract 14 Omidubicel-Onlv: Robustness of the Manufacturing Process
Authors: Landau Efrat , Goudsmid-Rosenheimer Noga , Hasson Nira , Bengaiev Roman , Guttman Miri , Yaacobov Liat , Nuriel Yonatan , Geffen Yona 
Published: September 2023

Abstract

Introduction
Omidubicel-onlv is a nicotinamide (NAM) -modified allogeneic hematopoietic progenitor cell therapy derived from cord blood. NAM expansion increases the number of stem and progenitor cells, inhibits differentiation, and potentiates migration, bone marrow homing, and engraftment efficiency. A global phase 3 trial demonstrated faster hematopoietic recovery, reduced rates of infection, and shorter hospitalizations for patients randomized to omidubicel-onlv compared to standard umbilical cord blood (UCB). Omidubicel-onlv is manufactured for each patient from a single, appropriately matched cord blood unit (CBU). The inherent donor variability as well as the different processing and testing methods used by different Cord Blood Banks (CBBs) present challenges in maintaining a consistent product.

Objectives
This extensive study was conducted to confirm the robustness of the manufacturing process and the proven acceptable range for the critical and key process parameters.

Methods
Seven process parameters were evaluated in total. Of these, three parameters were related to the CD34+ expansion phase: CD34+ seeding concentration, incubation temperature, and CO2 levels. Four additional parameters were related to final product formulation and cryopreservation: hold times during harvest and formulation, cell concentration in the drug product, DMSO concentration, and storage temperature. The impact of each process parameter on product performance was assessed by a side-by-side comparison of its target value (control) versus the tested range. Each parameter was evaluated using at least three batches derived from three CBUs. Statistical analysis of the coefficient of variation or recovery against the control was applied to the data sets.

Results
Statistical analyses demonstrated an overall variability of ≤30% in critical attributes including fold expansion, viability, phenotyping, and recovery of cells post-cryopreservation and stability.

Discussion
The omidubicel-onlv manufacturing process is robust, overcoming the variability of batches derived from different donors, different processing and testing methods at CBBs, and manufacturing process parameters.
Abstract 15 A State-Run Public Cord Blood Collection Program
Authors: Wilt Kristen , Ober Charis , Garcia John 
Published: September 2023

Abstract

Introduction
The Arizona Public Cord Blood Program was created in 2011 by the Arizona Biomedical Research Centre, a sub-section of the Arizona Department of Health Services, to advance the collection and increase the number of racially and ethnically diverse cord blood units available for transplantation, as well as promote awareness of the benefits of cord blood stem cells through our educational partner, Save the Cord Foundation (STCF).

Objectives
Create a sustainable program for women of all racial and ethnic backgrounds to have the opportunity to donate cord blood, with the primary goal of transplantation, and secondary goal of providing non-transplantable cord blood units for research. A second objective was to educate the residents of the state of Arizona about cord blood stem cells and the need for their preservation.

Methods
A portion of state lottery funds supports the program monetarily. Those funds are provided to four collection hospitals who employ "cord blood consenters" whose responsibility it is to consent patients, assist delivery providers with collections, and package and ship cord blood units to our partner cord blood bank at MD Anderson Cancer Center. There are also two clinical coordinators who educate and train hospital staff on quality collection practices, with special emphasis on the importance of high volume, sterile collections.
STCF provides education across the state to expectant parents, healthcare providers, schools, and the public about the need for cord blood stem cell donation for transplant and research.

Results
Since 2011, the Arizona Public Cord Blood Program has banked hundreds of racially and ethnically diverse cord blood units with the National Marrow Donor Program, and has had 86 life-saving cord blood units matched with patients in need around the globe. This innovative program has not only expanded cord blood awareness and promoted the preservation of cord blood; it has resulted in the creation of an economic engine for the state of Arizona that is an attractant for STEM based businesses and careers.

Discussion
A decade later, the Arizona Public Cord Blood Program has proven to be a sustainable model for collecting and providing suitable cord blood units for transplant to diverse patient populations.
Abstract 17 Umbilical Cord Blood Collection. How Do Different Factors Affect CD45 Cell Viability in Our Experience?
Authors: Gonel Lorena , Gonzalez Lihue 
Published: September 2023

Abstract

Introduction
Umbilical cord blood (UCB) is an important source of hematopoietic stem cells for transplantation in some hematological diseases. One of the main factors influencing sample quality and transplantation success, in addition to histocompatibility, is the number of viable CD34+ cells. Over the years, different factors that could directly affect viability have been studied and evaluated. It is important to be able to define favorable ranges for obtaining high viabilities and optimal samples for their use.

Objectives
The aim of our study is to evaluate the incidence of three factors temperature during transport, volume and time between collection and process of UCB over cellular viability previous to cryopreservation.

Methods
We analyzed 10483 UCB samples collected between 2018 and 2022. Cell viability values were analyzed in total CD45 using flow cytometry with 7-AAD and Annexin V. We evaluated the relationship between cell viability with the three factors mentioned above.

Results
We observed a tendency for viability to decrease as the blood volume collected decreases, and as the temperature and elapsed hours increase. In concordance, we found that viability is dependent on the 3 factors analyzed (p &lt;&lt;0.001), observing that its variability can be explained in 4% by the variation of elapsed hours as well as the collection volume, while temperature explains this variation in 1%.

Discussion
With our samples we can assume that the variations in the ranges analyzed would not affect them to a great extent, since they are not determinant for obtaining an average viability lower than that established as acceptable in our bank (75%). On the other hand, we also conclude that viability cannot be explained from the variation of a single factor, so it would be important to analyze the interactions between them. For the time being, and in order to improve the quality of the samples, we consider it necessary to emphasize the collection of a good volume of blood and the rapid transport of the samples for processing.
Abstract 18 Leveraging the BMDI Cord Blood Bank to Create a GMP-Compliant Cord Blood (CB)–Derived Induced Pluripotent Stem Cell (iPSC) Master Cell Bank (MCB) for Potential Allogeneic Therapies
Authors: Tian Pei , Whish-Wilson Junann , Choi Kawa , Tsoutras Denise , McDonald Trish , Abberton Keren , Elwood Ngaire 
Published: September 2023

Abstract

Introduction
The BMDI Cord Blood Bank (CBB) in Melbourne is a public cord blood bank that operates under a Good Manufacturing Practice (GMP) cell-manufacturing licence from the Therapeutic Goods Administration (TGA) and is internationally accredited by the Foundation for the Accreditation of Cellular Therapy (FACT). An iPSC MCB derived from cord blood (CB) could form the basis of future cell-based therapies. Banked CB is an ideal source of starting material for the creation of iPSCs, with a host of advantages not afforded by other cell sources.

Objectives
We have previously described the technical aspects of creating “GMP-like” iPSCs from banked CB (https://www.frontiersin.org/articles/10.3389/fcell.2022.835321/full). Our objective is to leverage the CBB to transition our “GMP-like” protocols, developed in the research lab, into a fully GMP-compliant environment.

Methods
A small lab within the CBB was seconded for the purpose of establishing an Institutional Biosafety Committee (IBC) – approved PC2 laboratory to create GMP-compliant iPSC lines from banked cord blood. CB donors have been re-consented to use a portion of their banked HLA homozygous CB to create iPSC lines (https://doi.org/10.1093/stcltm/szac060). The CBB Quality Framework was replicated as a side module, mimicking all key components.

Results
* Established an IBC-approved PC2 laboratory within the GMP-compliant CBB facility.
* Developed a Quality Systems framework in-line with the FACT Common Standards for Cellular Therapy, leveraging off that in place for the CBB.
* Tested and validated the process in its entirety, including robustness of the Quality Systems, by the creation of new CB-derived “GMP-mock” iPSC lines.
* Established collaborations for pre-clinical studies to use our CB-derived iPSC lines for therapies directed towards retinal and neurological repair, NK and CAR-NK immunotherapies.

Discussion
A PC2 GMP-compliant laboratory has been established. Challenges, and solutions, will be discussed. Quality systems have been developed that mimic those in place for the CBB. The robustness of the Quality framework and GMP manufacturing have been confirmed by a full mock-run to create new CB-derived iPSC lines. Lower grade reagents used for the mock-run have now been swapped out for more expensive, fully GMP-certified (CTS) reagents and creation of our first fully GMP CB-derived iPSC line is underway.
Abstract 28 A Novel Chemically Defined Culturing System to Support Hematopoietic Stem Cell Expansion
Authors: Uchiyama Asako , Ishihara Haruna , Nakayama Akiko , Watanabe Motoo , Arakawa Nobuyuki 
Published: September 2023

Abstract

Introduction
Hematopoietic stem cells (HSCs) are known to be multipotent and can reconstitute the entire blood and immune system following HSC transplantation (HSCT). However, the current HSCTs have many unresolved issues including difficulties in finding donors for bone marrow transplantation, preparing a sufficient HSC dose in cord blood transplantation, and the risk of graft-versus-host disease (GvHD) for all allogeneic HSCTs. In recent years, there have been substantial efforts to research and understand the biology of HSCs to develop cell therapy products that meet these challenges and provide an alternative to traditional HSCTs. Several culturing methods have been developed to stimulate HSC expansion ex vivo, but the use of biological materials, such as albumin, has not been ideal for pharmaceutical manufacturing, and it has been difficult inhibiting differentiation of HSCs into lineage-committed cells while culturing in a cytokine-filled medium. We have developed a novel albumin-free culturing system that supports proliferation of long-term HSCs ex vivo by replacing cytokines and albumin with chemical agonists and a caprolactam-based polymer.

Objectives
The objective of this study is to characterize our expanded cell population as part of an analysis to determine whether the population reconstitutes bone marrow and is therefore suitable for development of a cell therapy product.

Methods
Here we report the in vitro and in vivo characterization of proliferated HSCs using our novel culturing system compared with a nicotinamide system which is known to support HSC proliferation ex vivo. A colony forming assay, cell surface marker analysis using a flow cytometer, and in vivo repopulating analysis using the NOD/Shi-scid IL-2Rγnull (NOG) mouse were conducted.

Results
Surface marker analysis of the proliferated population shows more than 70% remaining as undifferentiated CD34+. Of which, a higher number of CD201+CD90+CD45RA- exists compared with the nicotinamide-cultured population. Colony forming unit assays indicate that our proliferated cell population contains a higher number of multipotent progenitors. The repopulating cell assay also shows that the proliferated cells have bone marrow reconstitution capability in bone marrow-ablated NOG mice.

Discussion
We believe that our chemically defined culturing system can selectively proliferate HSCs while restraining their differentiation and will contribute to the development of novel HSC therapy products.
Do epiphytic lichens negatively impact their hosts through allelopathy? The effect of Evernia esorediosa on growth and biochemical processes of Larix gmelinii
Authors: Vitalievich Sleptsov Igor , Mikhailovna Rozhina Sakhaiana , Andreevich Prokopiev Ilya , Vasilievich Mikhailov Vladislav , Vasilievich Alekseev Kirill 
Published: September 2023

Abstract
The question of the nature of the interaction between epiphytic lichens and their host trees remains highly debated. Some authors showed cases of allelopathy, but this needs further investigation. Our study covers the effects caused by the epiphytic lichen Evernia esorediosa (Müll. Arg.) Du Rietz on growth and biochemical processes in Larix gmelinii (Rupr.) Rupr. ex Kuzen trees in cryolithozone boreal forests. Usnic acid (UA) is shown to migrate from the thalli of E. esorediosa in the bark and phloem of L. gmelinii, from which it is transported to the root system of the tree, and then UA is moved upward through the xylem into tree needles. Accumulation of UA in L. gmelinii needles causes the following effects: inhibition of photosynthesis, cellular respiration and oxidative phosphorylation. These disruptions could reflect on the tree growth processes. The L. gmelinii trees inhabited by the epiphytic lichen E. esorediosa were found to show lower radial and apical growth parameters. Our results show that E. esorediosa exhibits an allelopathic effect toward L. gmelinii through the migration of UA from the lichen thalli to the tissues of the tree, which led to inhibition of energetic processes in cells. This caused the tree growth to slow down and could ultimately lead to its death.
IGF2BP2 promotes ovarian cancer growth and metastasis by upregulating CKAP2L protein expression in an m6A‐dependent manner
Authors: Shi Yaqian , Xiong Xueyou , Sun Yu , Geng Zhe , Chen Xiyi , Cui Xin , Lv Juan , Ge Lili , Jia Xuemei , Xu Juan 
Published: September 2023

AbstractOvarian cancer (OC) is the second leading cause of gynecological cancer‐related death in women worldwide. N6‐methyladenosine (m6A) is the most abundant internal modification in eukaryotic RNA. Human insulin‐like growth factor 2 mRNA‐binding protein 2 (IGF2BP2), an m6A reader, can enhance mRNA stability and promote translation by recognizing m6A modifications. Its tumor‐promoting effects have been demonstrated in several cancers. However, the roles of m6A modification and IGF2BP2 in OC remain unclear. Here, by using methylated RNA immunoprecipitation sequencing, we demonstrated that there is widespread dysregulation of m6A modification in OC tissues. The m6A modification and the mRNA and protein levels of IGF2BP2 were significantly elevated in OC. Overexpression of IGF2BP2 facilitated OC cell proliferation, migration, and invasion in vitro and accelerated tumor growth and metastasis in vivo. While IGF2BP2‐knockdown showed the opposite effect. Mechanistically, we identified cytoskeleton‐associated protein 2‐like (CKAP2L) as a target of IGF2BP2. IGF2BP2 promoted CKAP2L translation dependent on m6A modification, rather than affecting mRNA and protein stability. Overexpression of CKAP2L rescued the tumor‐suppressive effect of IGF2BP2 knockdown in OC cells. In conclusion, this study revealed the potential role of IGF2BP2 in tumor progression, at least partially via promoting the translation of CKAP2L in an m6A‐dependent manner.
A genome‐wide transposon mutagenesis screening identifies LppB as a key factor associated with Mycoplasma bovis colonization and invasion into host cells
Authors: Lan Shimei , Li Zhangcheng , Hao Huafang , Liu Shuang , Huang Zhicheng , Bai Yutong , Li Yanzhao , Yan Xinmin , Gao Pengcheng , Chen Shengli , Chu Yuefeng 
Published: September 2023

AbstractMycoplasma spp., the smallest self‐replicating and genome‐reduced organisms, have raised a great concern in both the medical and veterinary fields due to their pathogenicity. The molecular determinants of these wall‐less bacterium efficiently use their limited genes to ensure successful infection of the host remain unclear. In the present study, we used the ruminant pathogen Mycoplasma bovis as a model to identify the key factors for colonization and invasion into host cells. We constructed a nonredundant fluorescent transposon mutant library of M. bovis using a modified transposon plasmid, and identified 34 novel adhesion‐related genes based on a high‐throughput screening approach. Among them, the ΔLppB mutant exhibited the most apparent decrease in adhesion to embryonic bovine lung (EBL) cells. The surface‐localized lipoprotein LppB, which is highly conserved in Mycoplasma species, was then confirmed as a key factor for M. bovis adhesion with great immunogenicity. LppB interacted with various components (fibronectin, vitronectin, collagen IV, and laminin) of host extracellular matrix (ECM) and promoted plasminogen activation through tPA to degrade ECM. The 439–502 amino acid region of LppB is a critical domain, and F465 and Y493 are important residues for the plasminogen activation activity. We further revealed LppB as a key factor facilitating internalization through clathrin‐ and lipid raft‐mediated endocytosis, which helps the Mycoplasma invade the host cells. Our study indicates that LppB plays a key role in Mycoplasma infection and is a potential new therapeutic and vaccine target for Mycoplasma species.
Mitochondrial DNA – novel mechanisms of kidney damage and potential biomarker
Authors: Malik Afshan N. 
Published: September 2023

Purpose of review
MtDNA copy number (CN), a putative noninvasive biomarker of mitochondrial dysfunction, is associated with renal disease. The purpose of this review is to describe studies which measured human blood mtDNA-CN in the context of chronic kidney disease (CKD), and to evaluate its potential as a clinical biomarker of kidney disease.

Recent findings
Following on from small scale cross-sectional studies implicating mtDNA-CN changes in diabetic kidney disease, recent large scale population studies provide compelling evidence of the association of mtDNA-CN and risk of renal disease in the general population and poor outcomes in CKD patients.

Summary
The kidney has high bioenergetic needs, renal cells are rich in mitochondrial content containing 100s to 1000s of mtDNA molecular per cell. MtDNA has emerged as both a potential mediator, and a putative biomarker of renal disease. Damage to mtDNA can result in bioenergetic deficit, and reduced MtDNA levels in the blood have been shown to correlate with CKD. Furthermore, leakage of mtDNA outside of mitochondria into the cytosol/periphery can directly cause inflammation and is implicated in acute kidney injury (AKI). Recent large-scale population studies show the association of mtDNA-CN and renal disease and provide a strong basis for the future evaluation of circulating DNA-CN in longitudinal studies to determine its utility as a clinical biomarker for monitoring renal function.
PET/CT imaging fibroblast activation protein in initial colorectal cancer: compared to 18F-FDG PET/CT
Authors: Dong Ye , Sun Penghui , Wu Hubing , Zhong Jinmei , Cao Min , Tang Ganghua , Zhou Wenlan 
Published: September 2023

Objective
In this study, the potential advantage of FAPI over 18F-labelled deoxyglucose (18F-FDG) in evaluation of the initial staging colorectal cancer (CRC) was investigated.

Materials and methods
Thirty-two patients with histopathologically confirmed primary CRC were included in our study. They all underwent both 18F-FDG and FAPI PET/CT. Lesion detectability and tracer uptakes, mainly quantified by maximum standardized uptake value (SUVmax) and target-to-background ratio (TBR), were compared for paired lesions between both modalities using the Wilcoxon signed-rank test and paired t-test.

Results
Thirty-five CRC lesions in 32 patients were diagnosed. The sensitivity of FAPI PET/CT in diagnosis of the CRC lesions was 100% while 93.8% of 18F-FDG PET/CT. FAPI and 18F-FDG had a similar uptake in CRC lesion (mean SUVmax: 14.3 ± 8.6 vs. 15.4 ± 9.8, P = 0.604), but lesions contained mucus and/or signet-ring cell carcinoma seemed to have a trend of higher FAPI uptake although there was no statistical difference (mean SUVmax: 12.7 ± 5.6 vs. 8.5 ± 4.1, P = 0.152) and higher TBR (13.4 ± 6.2 vs. 4.9 ± 2.2, P = 0.004) than those of 18F-FDG. For regional lymph node metastases, both FAPI and FDG PET/CTs showed high sensitivity (7/8 vs. 7/8), specificity (7/8 vs. 6/8) and accuracy (14/16 vs. 13/16) (all P > 0.05). For distant metastasis, FAPI PET/CT depicted more positive lesions in distant lymph node (46 vs. 26), liver (13 vs. 7) and peritoneum (107 vs. 45) than 18F-FDG PET/CT. FAPI PET/CT also had a higher peritoneal cancer index score (median 11 vs 4; P < 0.001) than 18F-FDG PET/CT in evaluation of peritoneal metastases.

Conclusion
FAPI PET/CT showed high sensitivity in detection of primary CRC and superiority to 18F-FDG PET/CT in detection of metastases to distant lymph node, liver and peritoneum.