bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 10 Interim Results of a Phase I Study Investigating a Cord Blood-Derived Natural Killer Cell Therapy for Patients Hospitalized with COVID-19
Authors: Tercero Almudena , Finlay Dan , Asghedom Liya H , Romasanta Gladys R , Rice Natalie T , Ranjbaran Fatima , Stoltzman Carrie , Cook Jody , Blake Joe , Delaney Colleen , Hill Joshua A 
Published: September 2022

Abstract

Introduction
In the setting of viral infections, including infection with SARS-CoV-2, lymphocyte exhaustion and lymphopenia are common. Patients with COVID-19 who develop lymphopenia, particularly low numbers of circulating natural killer (NK) cells, are at high risk for disease progression. Thus, strategies that overcome profound lymphopenia and restore innate immune function may reduce the severity of COVID-19. One approach is the direct infusion of an exogenous source of healthy, functional NK cells intended to boost the patient’s immune system during the viral infection, enabling elimination of infected cells. “DVX201” is a cord blood-derived allogeneic NK cell therapy that is cryopreserved and intended for “off-the-shelf use” without HLA-matching.

Objective
The primary objective of this study is to investigate the safety and to identify the recommended phase II dose and/or the maximum tolerated dose (MTD) of DVX201 in patients hospitalized with COVID-19.

Methods
We are conducting an open-label, nonrandomized phase I safety and dose-finding (modified 3+3) study of DVX201 at three dose levels in patients hospitalized with COVID-19. Adult patients with documented SARS-CoV-2 infection were eligible if they were admitted to the hospital, were receiving ≤6 L supplemental oxygen by low flow delivery, and did not have other evidence of cytokine storm based on levels of serum IL-6, C-reactive protein, and ferritin.

Results
To date, 9 patients have been enrolled: 3 subjects at each dose level. All dose levels have been well tolerated, with no dose-limiting toxicities, infusion toxicities, or cytokine release syndrome observed. All patients were discharged from the hospital at an average of 5 days post infusion. Blood samples were drawn for correlative studies including persistence of DVX201, pre- and post-infusion immune system characterization, and cytokine panels. Accrual is continuing at the MTD.

Discussion
This trial will serve as the proof of concept for the use of DVX201 as an anti-viral treatment for COVID-19. These results will inform the potential role of DVX201 for treatment of other life-threatening viral infections by harnessing NK cells’ innate function to kill virally infected cells, regardless of the etiology of the infection.
Abstract 18 Developing a Potency Assay for Cord Tissue MSCs
Authors: Parrott Roberta , Noldner Pamela , Xu Li , Filiano Anthony , Shaz Beth , Kurtzberg Joanne 
Published: September 2022

Abstract

Introduction
The potency of mesenchymal stromal cells (MSCs) can be assessed by their ability to suppress proliferation of third party stimulated peripheral blood T cells. This correlates with decreased cellular production of IL-2Ra.

Objective
We optimized a potency assay for human cord tissue MSCs (hCT-MSC) in clinical trials for subjects with neuroinflammation. Originally, this T cell suppression assay required radioactive tritiated thymidine, rendering the assay difficult to use in a quality control laboratory for product release. Accordingly, we are developing a modified assay that eliminates the tritiated thymidine and instead tests for production of IL-2Rα in harvested supernatants.

Methods
The modified assay utilizes freshly thawed hCT-MSCs plated in a 96-well Corning CellBIND plate in Fuji Prime-XV XSFM MSC expansion medium at three concentrations. The hCT-MSCs are incubated 1-6 days at 37°C with humidified 5% CO2 until 80%-100% confluent. At this point, three different, previously qualified, normal control peripheral blood mononuclear cells (PBMCs) are suspended in RPMI 1640 with HEPES medium and 10% fetal bovine serum (FBS) with and without Dynabead (Human T-Activator CD3/CD28). After 4 additional days in culture, 75 µL of supernatant is removed and frozen at –80°C for future assaying of IL-10, TNFα, IFNg, and IL-2Ra using the Ella (Bio-Techne). IL-2Ra was determined to have the best correlation with the original method of suppression of proliferation. In the original radioactivity method after 4 days, the cells were pulsed with tritiated thymidine, harvested 6-10 hours after pulsing, and counted in the MicroBeta2 counter.

Results
Seventeen hCT-MSC lines were then tested in both assays. The passing criteria was &gt;70% suppression in the radioactivity assays or &gt;70% decrease in IL-2Ra production in the Ella assay. All 17 hCT-MSC lots passed in the radioactivity-based assay, while 16/17 lines passed using the IL-2Rα assay. Subsequently, the number of PBMCs plated per well and the number of days the PBMCs were in culture were optimized to maximize production of IL-2Rα.

Discussion
We developed a potency assay for MSCs that eliminates the use of radioactive reagents and usable as a release assay in manufacturing of hCT-MSC.
Abstract 31 Testing of Cord Blood Units for Non-Hematopoietic Markers
Authors: Frenet Emeline Masson , Watanabe Chiseko , Bentsen Helen , Chowtee Bryana , Liu WenJun , Romeo Cynthia , Sung Dorothy , Jimenez Alexandra 
Published: September 2022

Abstract

Introduction
Cord blood units (CBU) are tested at banking for markers relevant to donor safety (infectious disease markers) and hematopoietic stem cell transplantation (cellularity and HLA typing). As CBUs are being increasingly used for new, non-transplant purposes, additional markers are sometimes needed for CBU selection.

Objective
We describe here our procedure for testing CBU, looking for specific NK cell characteristics: KIR haplotype B (associated with more activating KIRs), and Fc gamma receptor III A (FCGR3A) 158 V/V (presence of a homozygous valine in position 158) polymorphism (which has a higher affinity for IgG), as requested by some of our clients for non-transplant studies.

Methods
First, a list of eligible CBUs was established, based on the order specifications. Testing was requested from an outside lab (Histogenetics, Ossining, New York). As CBU DNA is a precious resource, we wanted to limit the number of new samples to be sent by first testing leftover samples from HLA typing, then sending additional samples to the lab, to reach the required number of CBUs. Testing was done sequentially (Figure 1): first, KIR typing, then FCGR3A polymorphism on the CBU with KIR B haplotype.

Results
A total of 216 samples were selected for KIR testing (130 from stored DNA and 86 from newly sent DNA); 154 (71%) were found to have at least one B haplotype receptor. For those, FCGR3A polymorphism was tested; 60 samples (39%) were F/F, 70 (46%) F/V, and 23 (15%) V/V (Figure 1), in line with expected frequencies from the literature. Average TAT for KIR testing was 13 days and an additional 18 days for FCGRA3.

Discussion
Performing additional testing can easily be integrated into a bank’s routine and help select CBU for purposes other than transplantation. When several markers are needed, sequential testing is an efficient and cost-saving method.
A transition to online teaching and learning of mathematics in Norwegian higher education institutions: the perspectives of lecturers and students
Authors: Radmehr Farzad , Goodchild Simon 
Published: September 2022

Abstract
This paper reports a study of university lecturers’ and students’ experiences of teaching and learning mathematics following the abrupt requirement to switch to online teaching in 2020. A goal of the study is to share experiences that could be useful to improve the teaching and learning of mathematics in online settings. The qualitative research described is a phenomenological study and draws on interviews with ten mathematics lecturers and six undergraduate students who were enrolled in at least one university mathematical course during the lockdown in 2020. The interview data were analysed using a thematic approach. This paper reports findings regarding perceptions of lecturers and students about the challenges and benefits of online teaching and learning of mathematics, how the transition to online education has influenced assessment and sharing useful approaches for teaching and learning mathematics in online settings.
LncRNA HOTAIRM1 Involved in Nano NiO-Induced Pulmonary Fibrosis via Regulating PRKCB DNA Methylation-Mediated JNK/c-Jun Pathway
Authors: Zheng Jinfa , Wang Jinyu , Qin Xin , Li Kun , Gao Qing , Yang Mengmeng , Liu Han , Li Sheng , Chang Xuhong , Sun Yingbiao 
Published: September 2022

AbstractNickel oxide nanoparticles (Nano NiO) lead to pulmonary fibrosis, and the mechanisms are associated with epigenetics. This study aimed to clarify the regulatory relationship among long noncoding RNA HOXA transcript antisense RNA myeloid-specific 1 (HOTAIRM1), DNA methylation and expression of protein kinase C beta (PRKCB), and JNK/c-Jun pathway in Nano NiO-induced pulmonary fibrosis. Therefore, we constructed the rat pulmonary fibrosis model by intratracheal instillation of Nano NiO twice a week for 9 weeks and established the collagen deposition model by treating BEAS-2B cells with Nano NiO for 24 h. Here, the DNA methylation pattern was analyzed by whole-genome bisulfite sequencing in rat fibrotic lung tissues. Then, we integrated mRNA transcriptome data and found 93 DNA methylation genes with transcriptional significance. Meanwhile, the data showed that Nano NiO caused the down-regulation of lncRNA HOTAIRM1, the hypomethylation, and up-regulation of PRKCB2, JNK/c-Jun pathway activation, and collagen deposition (the up-regulated Col-I and α-SMA) both in vivo and in vitro. DNMTs inhibitor 5-AZDC attenuated Nano NiO-induced PRKCB2 expression, JNK/c-Jun pathway activation, and collagen deposition, but overexpression of PRKCB2 aggravated the changes mentioned indicators in Nano NiO-induced BEAS-2B cells. Furthermore, JNK/c-Jun pathway inhibitor (SP600125) alleviated Nano NiO-induced excessive collagen formation. Additionally, overexpression of HOTAIRM1 restrained the PRKCB hypomethylation, the activation of JNK/c-Jun pathway, and collagen formation induced by Nano NiO in BEAS-2B cells. In conclusion, these findings demonstrated that HOTAIRM1 could arrest Nano NiO-induced pulmonary fibrosis by suppressing the PRKCB DNA methylation-mediated JNK/c-Jun pathway.
Importation and circulation of rubella virus lineages 1E-L2 and 2B-L2c between 2018 and 2021 in China: Virus evolution and spatial–temporal transmission characteristics
Authors: Liu Ying , Han Zhenzhi , Kang Chuyun , Cui Aili , Zhang Yan , Liu Li , Chen Ying , Deng Lili , Zhao Hua , Zhou Jun , Li Fangcai , Zhou Shujie , Feng Daxing , Tian Xiaoling , Feng Yan , Cui Xiaoxian , Lei Yue , Wang Yan , Yuan Fang , Fan Lixia , Tang Xiaomin , Chen Meng , Peng Xiaofang , Guo Yu , Gao Hui , Wang Suting , Li Liqun , Zhang Ting , Deng Xiuying , Chen Haiyun , Wang Shuang , Ma Yu , Zhu Zhen , Xu Wenbo 
Published: September 2022

Abstract
To better understand the importation and circulation patterns of rubella virus lineages 1E-L2 and 2B-L2c circulating in China since 2018, 3,312 viral strains collected from 27 out of 31 provinces in China between 2018 and 2021 were sequenced and analyzed with the representative international strains of lineages 1E-L2 and 2B-L2c based on genotyping region. Time-scale phylogenetic analysis revealed that the global lineages 1E-L2 and 2B-L2c presented distinct evolutionary patterns. Lineage 1E-L2 circulated in relatively limited geographical areas (mainly Asia) and showed geographical and temporal clustering, while lineage 2B-L2c strains circulated widely throughout the world and exhibited a complicated topology with several independently evolved branches. Furthermore, both lineages showed extensive international transmission activities, and phylogeographic inference provided evidence that lineage 1E-L2 strains circulating in China possibly originated from Japan, while the source of lineage 2B-L2c isolated since 2018 is still unclear. After importation into China in 2018, the spread of lineage 1E-L2 presented a three-stage transmission pattern from southern to northern China, whereas lineage 2B-L2c spread from a single point in western China to all the other four regions. These two transmission patterns allowed both imported lineages to spread rapidly across China during the 2018–9 rubella epidemic and eventually established endemic circulations. This study provides critical scientific data for rubella control and elimination in China and worldwide.
COVID-19 Vaccines for Children with Developmental Disabilities: Survey of New York State Parents' Willingness and Concerns
Authors: Bonuck Karen , Iadarola Suzannah , Gao Qi , Siegel Joanne F. 
Published: September 2022

ABSTRACT:

Objective:
While 1 in 6 US children have a developmental disability (DD), and such children are disproportionately affected by COVID-19, little is known about their vaccination status. We surveyed New York State parents of children with DDs to ascertain willingness and concerns regarding COVID-19 vaccines.

Methods:
An online survey was distributed to statewide DD networks from June to September 2021 (vaccines were authorized for adolescents in May 2021). We report associations between vaccine willingness and concerns and race/ethnicity, child age, in-person schooling, routine/flu vaccinations, and DD diagnoses. Willingness was categorized as “got/will get ASAP” (high), “wait and see/only if required,” or “definitely not.”

Results:
A total of 352 parents (49.1% White) responded. Willingness differed by age (p < 0.001). High willingness was reported for 73.9%, 50.0%, and 36.0% of children aged 12 to 17, 6 to 11, and 0 to 5 years, respectively. Willingness differed by autism diagnosis (p < 0.01) and routine and flu vaccination status (p < 0.001). Predominant concerns included side effects (89%) and children with disabilities not being in trials (80%). Less common concerns were COVID not serious enough in children to warrant vaccine (23%) and misinformation (e.g., microchips, 5G, DNA changes) (24%). Concerns about vaccine safety differed by age (p < 0.01) and were highest for older and then the youngest children. In age-stratified adjusted models, attention-deficit/hyperactivity disorder was negatively associated with high willingness for age 5 or younger (OR = 0.02, 95% confidence interval, <0.001–0.622).

Conclusion:
Parents of children with DD in New York seemed highly willing for them to receive COVID-19 vaccines. Although few factors predicted willingness to vaccinate, addressing safety and developmental concerns regarding young children is warranted. Given their increased vulnerability, improved COVID-19 surveillance for children with DD is warranted.
Perinatal Physiological and Psychological Risk Factors and Childhood Sleep Outcomes: A Systematic Review and Meta-analysis
Authors: Dai Ying , Trout Kimberly Kovach , Liu Jianghong 
Published: September 2022

Abstract:

Objectives:
The purpose of this study was to investigate the influence of maternal physiological and psychological factors during pregnancy and after birth on infant and children's sleep outcomes.

Methods:
Six databases were searched from inception to April 2021. Longitudinal studies that investigated the association of risk factors during and after pregnancy and children's sleep-related outcomes were included. Hedge's g and odds ratio were pooled as effect size with random effects model.

Results:
A total of 32 articles were included. Both prenatal maternal alcohol use (odds ratio [OR] = 1.85, 95% confidence interval [CI]: 1.04–3.28) and tobacco smoking (OR = 1.28, 95% CI: 1.01–1.62) were associated with shorter child sleep duration. Prenatal and postnatal maternal depression symptoms were associated with increased child sleep problems at age 6 months (OR = 1.97, 95% CI: 1.19–3.24, and 2.05, 95% CI: 1.37–3.07, respectively). Prenatal and postnatal maternal major depression disorders were associated with shorter sleep duration (Hedge's g = −0.97, 95% CI: −1.57 to −0.37) and lower sleep efficiency (Hedge's g = −1.44, 95% CI: −1.93 to −0.95). Prenatal anxiety had no impact on child sleep problems (OR = 1.34, 95% CI: 0.86–2.10).

Conclusion:
Maternal pregnancy and obstetric factors and psychological factors are potential risk factors of poor child sleep health. Future research is warranted to better understand the impact of these risk factors on long-term child sleep outcomes and their potential mediating mechanisms.
Vanadium in groundwater aquifers increases the risk of MAC pulmonary infection in O’ahu, Hawai’i
Authors: Lipner Ettie M. , French Joshua P. , Nelson Stephen , Falkinham III Joseph O. , Mercaldo Rachel A. , Blakney Rebekah A. , Daida Yihe G. , Frankland Timothy B. , Messier Kyle P. , Honda Jennifer R. , Honda Stacey , Prevots D. Rebecca 
Published: September 2022

Rationale:
Hawai’i has the highest prevalence of nontuberculous mycobacterial (NTM) pulmonary disease in the United States. Previous studies indicate that certain trace metals in surface water increase the risk of NTM infection.

Objective:
To identify whether trace metals influence the risk of NTM infection in O’ahu, Hawai’i.

Methods:
A population-based ecologic cohort study was conducted using NTM infection incidence data from patients enrolled at Kaiser Permanente Hawai’i during 2005–2019. We obtained sociodemographic, microbiologic, and geocoded residential data for all Kaiser Permanente Hawai’i beneficiaries. To estimate the risk of NTM pulmonary infection from exposure to groundwater constituents, we obtained groundwater data from three data sources: (1) Water Quality Portal; (2) the Hawai’i Department of Health; and (3) Brigham Young University, Department of Geological Science faculty. Data were aggregated by an aquifer and were associated with the corresponding beneficiary aquifer of residence. We used Poisson regression models with backward elimination to generate models for NTM infection risk as a function of groundwater constituents. We modeled two outcomes: Mycobacterium avium complex (MAC) species and Mycobacterium abscessus group species.

Results:
For every 1-unit increase in the log concentration of vanadium in groundwater at the aquifer level, infection risk increased by 22% among MAC patients. We did not observe significant associations between water-quality constituents and infection risk among M. abscessus patients.

Conclusions:
Concentrations of vanadium in groundwater were associated with MAC pulmonary infection in O’ahu, Hawai’i. These findings provide evidence that naturally occurring trace metals influence the presence of NTM in water sources that supply municipal water systems.
Umbilical cord blood: an undervalued and underutilized resource in allogeneic hematopoietic stem cell transplant and novel cell therapy applications
Authors: Shi Patricia A. , Luchsinger Larry L. , Greally John M. , Delaney Colleen S. 
Published: September 2022

Purpose of review
The purpose of this review is to primarily discuss the unwarranted decline in the use of umbilical cord blood (UCB) as a source of donor hematopoietic stem cells (HSC) for hematopoietic cell transplantation (HCT) and the resulting important implications in addressing healthcare inequities, and secondly to highlight the incredible potential of UCB and related birthing tissues for the development of a broad range of therapies to treat human disease including but not limited to oncology, neurologic, cardiac, orthopedic and immunologic conditions.

Recent findings
When current best practices are followed, unrelated donor umbilical cord blood transplant (CBT) can provide superior quality of life-related survival compared to other allogeneic HSC donor sources (sibling, matched or mismatched unrelated, and haploidentical) through decreased risks of relapse and chronic graft vs. host disease. Current best practices include improved UCB donor selection criteria with consideration of higher resolution human leukocyte antigen (HLA) typing and CD34+ cell dose, availability of newer myeloablative but reduced toxicity conditioning regimens, and rigorous supportive care in the early posttransplant period with monitoring for known complications, especially related to viral and other infections that may require intervention. Emerging best practice may include the use of ex vivo expanded single-unit CBT rather than double-unit CBT (dCBT) or ‘haplo-cord’ transplant, and the incorporation of posttransplant cyclophosphamide as with haploidentical transplant and/or incorporation of novel posttransplant therapies to reduce the risk of relapse, such as NK cell adoptive transfer. Novel, non-HCT uses of UCB and birthing tissue include the production of UCB-derived immune effector cell therapies such as unmodified NK cells, chimeric antigen receptor-natural killer cells and immune T-cell populations, the isolation of mesenchymal stem cells for immune modulatory treatments and derivation of induced pluripotent stem cells haplobanks for regenerative medicine development and population studies to facilitate exploration of drug development through functional genomics.

Summary
The potential of allogeneic UCB for HCT and novel cell-based therapies is undervalued and underutilized. The inventory of high-quality UCB units available from public cord blood banks (CBB) should be expanding rather than contracting in order to address ongoing healthcare inequities and to maintain a valuable source of cellular starting material for cell and gene therapies and regenerative medicine approaches. The expertise in Good Manufacturing Practice-grade manufacturing provided by CBB should be supported to effectively partner with groups developing UCB for novel cell-based therapies.
Use of polylactid acid membrane improves outcome of split-thickness skin graft donor sites: a prospective, comparative, randomized study
Authors: Moellhoff Nicholas , Lettner Maria , Frank Konstantin , Giunta Riccardo E. , Ehrl Denis 
Published: September 2022

Background:
Polyurethane film (PU) dressings are commonly applied for coverage of split-thickness skin graft (SSG) donor sites, while previous studies have suggested reduced morbidity using a polylactic acid membrane (PLM). To further investigate the optimal treatment approach, the presented study compared outcome of donor sites in patients receiving either PLM or PU.

Methods:
This randomized clinical trial allocated patients requiring SSG to receive either PLM or PU at the donor-site. Primary endpoint was difference in donor site scar appearance between groups 3 months postoperatively (Vancouver Scar Scale – VSS). Secondary endpoints included pain, the number of and time requried for wound dressing changes, and costs related to the wound dressing.

Results:
30 patients were allocated to each group. The median VSS scored lower for patients receiving PLM (PU: 3 (Q1: 2; Q3: 4) vs. PLM: 2 (Q1: 1; Q3: 3); p=0.049). Pain during change of wound dressing (PU: 2.0 ± 0.2 vs. PLM: 0.5 ± 0.2; p<0.001) and mobilization (PU: 0.8 ± 0.2 vs. PLM: 0.3 ± 0.1; p=0.032) was reduced in the PLM group. Patients with PLM required less dressing changes per day of hospital stay (PU: 0.44 ± 0.06 vs. PLM: 0.28 ± 0.02; p=0.015). Mean time for wound dressing changes per patient was higher in the PU group (PU: 74.50 ± 5.72 vs. PLM: 21.43 ± 2.61 min; p<0.001). Costs were higher in the PLM group (PU: 67.83 ± 5.56 vs. PLM: 162.79 ± 21.76 €; p<0.001).

Conclusions:
PLM improves outcome of SSG donor sites, however, higher treatment costs must be taken into consideration.