bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 17 Comparison of Different Support Materials and Cryoprotectants for Amniotic Membrane Cryopreservation
Authors: Ogliari Karolyn , Grudzinski Patrícia , Immig Mônica , Halon Maria , Loth Fabrízio , Tovo Monique , da Silva Camila , Beckenkamp Liziane 
Published: September 2022

Abstract

Introduction
The amniotic membrane (AM) is a thin membrane derived from the placenta, rich in stem cells and structural components that stimulate tissue regeneration. This tissue has emerged as a biological dressing for several clinical applications. Many preservation techniques have been proposed for AM; however, searching for a method capable of preserving their physical and biological properties remains challenging.

Objective
This work investigated different ways to support the AM in packing, as well as two different cryoprotectants to preserve its histological, cytological, and biological characteristics.

Methods
Human placentas were processed for AM isolation and stored under various conditions: gauze (G) and petrolatum gauze (PG) were evaluated as support materials for the AM, while DMSO and glycerol were analyzed as cryoprotectants for both materials. In addition, after selecting the best support material, two forms of product presentation were also explored: flat fragment (FF) and roll (R). All protocols were stored in liquid nitrogen for at least 2 weeks. After this period, tissue was thawed, and structural integrity, cellular viability, and secretome analysis were performed.

Results
Cellular viability with PG was significantly reduced compared with fresh AM (Fresh: 63.6% ± 11.8%; PG+DMSO: 37.2% ± 17.9%; PG+glycerol: 23.2% ± 18.9%) (Figure 1A). Regarding gauze presentation, no difference in cell viability was found between cryoprotectants in the flat fragment groups (FF+DMSO: 53.4% ± 20.2% and FF+Glycerol: 55.5% ± 15.8%) (Figure 1B). As for the roll groups, cell viability was significantly better for DMSO (R+DMSO: 63.9% ± 11.8% and R+Glycerol: 37.1% ± 19.5V) (Figure 1B). Structural integrity evaluated by tissue immunofluorescence and picrosirius confirmed that the extracellular matrix components, such as laminin (Figure 1D), fibronectin (Figure 1E), and collagen (Figure 1F and 1G), were preserved with both cryoprotectants. Likewise, this protocol conserved progenitor/stem cells, assessed by the CD117 marker (Fresh: 25.4% ± 8.7%, DMSO:18.1% ± 9.5%, and Glycerol: 23.1% ± 11.7%) (Figure 1C). Secretome analysis showed a slight reduction of the proteins secreted by cryopreserved AM compared with fresh AM, although the difference was not significant (Figure 1H). Essential proteins involved in tissue regeneration (fibronectin, laminins, collagens, cadherins, and cytokeratins) and immune and antimicrobial control (PTX3, TMP1, SOD, lysozyme C, and immunoglobulins) could be detected from both AM (Figure 1I).

Discussion
PG support was harmful to cell viability. DMSO exhibited better results in cell viability and biological functions regardless of tissue presentation and cryopreservation.
Abstract 19 Cleveland Cord Blood Center (CCBC) Best Practices Throughout the COVID-19 Pandemic and How It Impacted Collection of Cord Blood Units
Authors: Bobik-Kurz Kathy , Laster Candice , Chase JoAnn , Boucher Susan , Wood Bridget , Laughlin Mary , Finney Marcie 
Published: September 2022

Abstract

Introduction
Our commitment to provide quality cord blood units (CBUs) to patients in need was challenged with the outbreak of COVID-19 and the pandemics continued impact through early 2022. We continually monitored the ever-evolving COVID-19 public health threat to make adjustments to our practices to achieve optimal collections while maintaining the safety and quality of our CBUs.

Objective
The CCBC continued collections at all five collection sites with a brief mandated pause at our California site due to hospital restrictions. We maintained minimal staffing at the cord blood center to reduce the number of employees impacted should an exposure occur. Donors were screened upon admission for symptoms, exposure, positive testing, and recent vaccination, and donors with identified risks were excluded from collection.

Methods
Our study design takes a retrospective look at data collected from the onset of the COVID-19 pandemic through December 2021 compared to data from 2018-2019. Factors included were birth numbers, number of patients testing positive for COVID-19, and staffing shortages due to coordinator illness with COVID-19.

Results
We saw limited impact to our collection staff at the hospital or on site at the CCBC. Our biggest reduction of donors consented was between 2019 and 2020, which we attribute to the COVID peak and introduction of vaccinations. Most sites were trending downward for consenting on a yearly basis before COVID-19 at a rate of 6%-10% per year; during 2019-2020 we saw 19%, but the trend has returned to 8% from 2020-2021. This same trending occurred during the ZIKA outbreak. There was no further data review to determine if these mothers would have been excluded for other reasons. We collected a total of 15,561 units between 2018 and 2019 and a total of 10,121 units between 2020 and 2021.

Discussion
Overall productivity of the collections was not dramatically affected by our response to the COVID-19 pandemic. Further research at time of pre-consent, to determine if the mother would have been ineligible to donate for reasons other than COVID-19, would have given us a more accurate count of donors lost for reasons related to the COVID-19 pandemic.
Abstract 22 CellStor Transfer Freezing Bag: Reliable Closed System for Complex Cord Blood Sample Processing and CD34+ Hematopoietic Stem Cell Cryopreservation
Authors: Kasthuri Srikumar , Abhaya Mayur , Padhiar Chirayu , Rajan Balaji , Anbalagan Jayanthi , Rengarajan Srinivas 
Published: September 2022

Abstract

Introduction
Hematopoietic stem cell (HSC) transplants are effective in the treatment of numerous disorders. Proper processing and storage of umbilical cord blood (UCB) and peripheral blood (PB) HSCs is invaluable for therapeutic applications. Although automated sample processing methods exist, they are unable to accommodate low volume, viscous, fibrin clotted, partially hemolyzed, or otherwise complex samples, resulting in the loss of precious HSCs. The CellBios single-use transfer freezing bag was designed to process peripheral and cord blood samples and freeze HSCs, including from those with the above-mentioned problems. Here we demonstrate the utility of these transfer freezing bags to salvage problematic UCB samples and recover precious HSC material suitable for banking and therapeutics.

Objective
The objective of this study was to develop a closed UCB sample processing and cryopreservation solution that is amenable to easy manual operation, can deliver excellent HSC viability and recovery, can eliminate contaminating red blood cells (RBCs), and is capable of processing complex/defective starting samples that are incompatible with conventional automated processing systems into therapeutic grade HSC banks.

Methods
We studied 100 randomly selected UCB samples, from various centers throughout India, that were processed and prepared for cryopreservation using our transfer freezing bag. We recorded the pre- and post-sample processing volumes, total nucleated cell counts (TNCC), hematocrit (HCT), CD34+ cell viability, and recovery.

Results
Study results showed the following: 94% vs 98% CD34+ cell viability post processing, 77% vs 85% total mononuclear cell viability, 69% vs 85% TNCC recovery in problematic vs normal samples, respectively. It was possible to achieve low RBC carryover –91% HCT reduction post-processing in normal samples; more importantly, problematic samples also had RBC removal evidenced by HCT reduction of 45%.

Discussion
We have demonstrated efficient removal of RBCs to alleviate post-transplantation issues and maximized CD34+ HSC recovery in both normal and problematic UCB samples. Crucially, it was possible to salvage precious CB HSCs from defective samples that would be lost had they been processed in conventional automated workflows. The CellBios CellStor Transfer Freezing Bag Set offers best in class performance in preparing umbilical cord blood samples for cryostorage.
Abstract 23 A First Insight into the Validity of Post-Thaw Cell Recovery, Viability, and Potency Over Time
Authors: Liu Lin , McDonald Trish , Elwood Ngaire 
Published: September 2022

Abstract

Introduction
Testing of a thawed segment or representative sample of a cord blood unit (CBU) for cell recovery, viability, and potency forms part of pre-release testing. Not all CBUs that have had pre-release testing completed are shipped for transplant, due to postponed or cancelled shipment request, and are therefore kept in the inventory until they are searched again. In an effort to identify these CBUs for future expedited release, the World Marrow Donor Association (WMDA) initiated a project to flag them as “Ready to Ship” in the WMDA Search & Match Service. However, it is not known how long post-thaw results are valid before they must be repeated on another thaw. Such information can be beneficial not only for transplant centers to better assess CBU suitability but also for Cord Blood Banks (CBBs) to avoid unnecessarily exhausting their precious samples.

Objective
This study aimed to provide a first insight into the validity of post-thaw results over various lengths of time.

Methods
Nineteen CBUs, collected between 2003 and 2015 at the BMDI CBB and that had post-thaw testing performed twice, were analyzed for change in the total nucleated cell (TNC) recovery, total CD34 cell recovery, CD34 cell viability, and CFU-GM counts between two thaws.

Results
The 19 CBUs were grouped into 4 groups based on their storage time between thaws. An average decrease in TNC recovery of 5.3% from first thaw to second thaw was observed for the entire dataset (P = .015). Four CBUs with a greater than 10% decrease had a bag TNC greater than 25 × 108. Individual CBU data is shown in Figure 1. No significant change between thaws was seen with total CD34 recovery (P = .738) or CD34 viability (n = 9 pairs, P = .354). A large variation in CFU-GM counts was observed between thaws. It is worth noting that all CBUs met CBB release criteria of &gt;60% TNC recovery and that CD34 viabilities were above 70% (FACT requirement) in both thaws.

Discussion
While results need to be confirmed on a larger dataset, our preliminary data shows very little change in post-thaw cell recovery and viability over various lengths of time (2 months-12 years), suggesting post-thaw results may be valid for longer than 10 years.
Abstract 24 Improving Cord Blood Unit Selection and Optimizing Manufacturing of a Unique Cord Blood-Derived Product (DUOC-01)
Authors: Ozamiz April , Shoulars Kevin , Noldner Pamela , Shaz Beth , Kurtzberg Joanne 
Published: September 2022

Abstract

Introduction
DUOC-01 are microglia-like cells derived from umbilical cord blood CD14-positive monocytes, which have been shown to induce remyelination in murine models of demyelination. Intrathecal DUOC-01 administration is being tested clinically in two phase I studies. First, DUOC-01 is being tested as a bridging therapy for pediatric patients with inherited leukodystrophies undergoing unrelated donor cord blood transplantation. Second, DUOC-01 is being tested in a phase Ia dose escalation study in patients with primary progressive multiple sclerosis.

Objective
DUOC-01 is manufactured from an HLA-matched cryopreserved cord blood unit (CBU). The CBU is thawed and cultured for 21 days under specific conditions, and the resulting DUOC-01 is harvested and formulated with hydrocortisone for intrathecal administration. Cell dosing per patient is limited by DUOC-01 yield, which is highly variable; therefore, there is great need to increase DUOC-01 yield and optimize manufacturing for more consistency.

Methods
(1) For the identification of optimal CBU selection, units are screened using small scale DUOC-01 cultures derived from CBU bag segments, which are then scored (0-4). In order to assess the value, we performed screening followed by DUOC-01 manufacturing and correlated the screening score to the DUOC-01 yield. (2) We assessed multiple variables to optimize DUOC-01 manufacturing including media volume and temperature, fetal bovine serum (FBS) lot variability, and culture container material.

Results
(1) 5/13 segments scored high (defined as ≥2) while the remaining 8/13 scored low (&lt;2). All 5 high-scored CBUs resulted in high yield (defined as ≥1.64 total cells/cm2). Of the 8 low-scored segments, 4 were low yield and 4 were high yield. (2) Comparison of different FBS lots did not show a significant change in DUOC-01 yield. Furthermore, media volume and temperature did not influence product yield. The choice of container material substantially impacted culture yields and cell viability (Figure 1).

Discussion
In order to increase cell yield and improve product consistency, we confirmed the value of the CBU segment screening assay and discovered the potential importance of culture container material. More experiments are needed to optimize and finalize product manufacturing.
Comparative analysis of genome-encoded viral sequences reveals the evolutionary history of flavivirids (family Flaviviridae)
Authors: Bamford Connor G G , de Souza William M , Parry Rhys , Gifford Robert J 
Published: September 2022

Abstract
Flavivirids (family Flaviviridae) are a group of positive-strand ribonucleic acid (RNA) viruses that pose serious risks to human and animal health on a global scale. Here, we use flavivirid-derived deoxyribonucleic acid (DNA) sequences, identified in animal genomes, to reconstruct the long-term evolutionary history of family Flaviviridae. We demonstrate that flavivirids are &gt;100 million years old and show that this timing can be combined with dates inferred from co-phyletic analysis to produce a cohesive overview of their evolution, distribution, and diversity wherein the main flavivirid subgroups originate in early animals and broadly co-diverge with major animal phyla. In addition, we reveal evidence that the ‘classical flaviviruses’ of vertebrates, most of which are transmitted via blood-feeding arthropod vectors, originally evolved in haematophagous arachnids and later acquired the capacity to be transmitted by insects. Our findings imply that the biological properties of flavivirids have been acquired gradually over the course of animal evolution. Thus, broad-scale comparative analysis will likely reveal fundamental insights into their biology. We therefore published our results via an open, extensible, database (Flavivirid-GLUE), which we constructed to facilitate the wider utilisation of genomic data and evolution-related domain knowledge in flavivirid research.
Revisiting miRNA-21 as a Therapeutic Strategy for Myocardial Infarction: A Systematic Review
Authors: Sothivelr Vivisana , Hasan Mohammad Y. , Mohd Saffian Shamin , Zainalabidin Satirah , Ugusman Azizah , Mahadi Mohd K. 
Published: September 2022

Abstract:
Several types of cardiovascular cells use microRNA-21 (miR-21), which has been linked to cardioprotection. In this study, we systematically reviewed the results of published papers on the therapeutic effect of miR-21 for myocardial infarction. Studies described the cardioprotective effects of miR-21 to reduce infarct size by improving angiogenesis, antiapoptotic, and anti-inflammatory mechanisms. Results suggest that cardioprotective effects of miR-21 may work synergistically to prevent the deterioration of cardiac function during postischemia. However, there are other results that indicate that miR-21 positively regulates tissue fibrosis, potentially worsening a postischemic injury. The dual functionalities of miR-21 occur through the targeting of genes and signaling pathways, such as PTEN, PDCD4, KBTBD7, NOS3, STRN, and Spry-1. This review provides insights into the future advancement of safe miR-21–based genetic therapy in the treatment of myocardial infarction.
Implementation of an In Vitro Experimental Setup Simulating Pulmonary Dissolution Following the Inhalation of Radioactive Particulate Material
Authors: Saviotti Agnese , Porta Alessandro Antonio , Campi Fabrizio , Derudi Marco 
Published: September 2022

Abstract
Given the need for criteria to control the radiation doses due to radionuclide inhalation, in 1994 the International Commission on Radiological Protection presented a classification for radioactive compounds based on their pulmonary absorption rates. The Commission classified the compounds into fast, moderate, and slow categories and assigned to each material a default absorption class. Nevertheless, the proposed categories do not always resemble the actual behavior of the classified materials in the pulmonary environment. Therefore, the Commission itself suggested the assessment of the inhalation risk of a particulate substance referring to an in vivo study using the same material. Since it is not possible to trace in literature in vivo studies analyzing the physiological behavior of the totality of inhalable radioactive materials, the Commission suggested adopting in vitro systems simulating the pulmonary mechanism. For this reason, in the last 50 y, many simulating setups have been implemented, but none of these seemed to reproduce the lung dissolution dynamics effectively as the results were not comparable with the ones obtained using in vivo techniques. This paper aims to describe an innovative experimental apparatus implemented as an attempt to add another step toward the realization of a gold standard. In particular, the system was validated with BaSO4 particulate, and the resulting error with respect to the physiological expected value figured as less than 4%. The system was then employed for the lung dissolution tests of radioactive graphite extracted from Politecnico di Milano’s nuclear reactor to assess the radiobiological risk due to a slow lung absorption process that workers might run into during the reactor decommissioning.
A double hyperautofluorescent ring in a 33-year-old-female patient
Authors: da Palma Mariana M. , Marrra Molly , Pennesi Mark E. 
Published: September 2022

ABSTRACT

Purpose:
To describe the clinical phenotype and molecular diagnosis of a patient with atypical presentation of Enhanced S-cone Syndrome.

Methods:
This is a case report of a patient that underwent best-corrected visual acuity, slit-lamp exam, fundus exam, autofluorescence, optical coherence tomography, kinetic perimetry, full-field electroretinography. Genetic testing was performed via next-generation sequencing.

Results:
A 33-years-old female patient presented with mild nyctalopia but normal rod function measured by electroretinogram and foveoschisis on OCT. She also presented a double hyperautofluorescent ring on autofluorescence. Genetic testing found a pathogenic variant c.925C>G (p.Arg309Gly) and a likely pathogenic variant c.299C>T (p.Arg77Trp) in NR2E3 gene.

Discussion:
Enhanced S-cone Syndrome may present without the pathognomonic findings of decreased rod function on ERG, suggesting the importance of genetic testing in retinal diseases for diagnosis.
Leber hereditary optic neuropathy: new and emerging therapies
Authors: Davila-Siliezar Pamela , Carter Michael , Milea Dan , Lee Andrew G. 
Published: September 2022

Purpose of review
To review recent therapeutic advances in Leber hereditary optic neuropathy (LHON).

Recent findings
Idebenone, a synthetic analog of ubiquinone (Coenzyme Q10) is an antioxidant and component of the mitochondrial electron transport chain. Since the initial approval of the drug in 2015 in Europe, recent trials have evaluated its role as prolonged treatment in LHON. Gene therapy has recently emerged as a promising alternative for the treatment of LHON. Among several investigations, RESCUE and REVERSE are two phase 3 clinical trials of gene therapy in patients with LHON in early stages. Results in these trials have shown a bilateral visual acuity improvement with unilateral intravitreal injections at 96 weeks and sustained visual improvement after 3 years of treatment. The most recent REFLECT phase 3 clinical trial in LHON has shown significant improvement of vision after bilateral intravitreal injections compared with the group that received unilateral injections.

Summary
Historically, LHON has been considered an untreatable disease, but recent developments show that new pharmacological and gene therapy approaches may lead to visual recovery. Further studies are needed to support these data.
A Mother-Child Dyadic Approach to Evaluating Subclinical Cardiovascular Disease in Young Children
Authors: Muchira James M. , Mogos Mulubrhan F. , Park Chorong , Logan Jeongok , Piano Mariann R. 
Published: September 2022

Background
Cardiovascular (CV) risk factors can be transmitted from mothers to their children. However, it is challenging to measure and identify subclinical CV risk in young children using traditional CV risk methods and metrics.

Objective
The purpose of this study was to determine the feasibility of recruiting mother-child dyads and measuring arterial stiffness (pulse wave velocity, augmentation index/pressure), blood pressure (BP), BP circadian pattern, specifically nocturnal BP dipping, and CV health metrics in mothers and in children aged 1 to 5 years.

Methods
All BP and arterial stiffness measures were obtained using the noninvasive automated oscillometric Mobil-O-Graph device. Also measured were blood cholesterol level; glucose level; body mass index (BMI); and smoking, diet, and physical activity history. Descriptive statistics were used for assessing recruitment feasibility and Pearson correlations for mother-child associations.

Results
Thirty-five mother-child dyads completed the protocol. Recruitment reach was 89% and retention rate was 80%. Mothers were 34.3 ± 5.4 years old with a mean systolic BP (SBP) of 114.6 ± 9.5 mm Hg and BMI of 26.0 ± 6.5. Children were 3 ± 1.4 years old with a mean SBP of 103.3 ± 9.4 mm Hg and BMI z-scores of −0.3 ± 1.5. Arterial stiffness parameters were within normal ranges for mothers and children. Twenty-three percent of mothers did not exhibit nocturnal dipping (<10% decrease between day and nighttime SBP). Maternal SBP was positively correlated with child BMI z-scores (r = 0.42, P = .022) as well as mother-child augmentation pressure (r = 0.51, P = .010).

Conclusions
Our findings support using a mother-child approach and novel noninvasive approaches to assess and target CV risk in mothers and their young children.
Quality Improvement to Promote Sepsis Reassessment
Authors: DeGregoris Jana P. , Bandong Lyza , White Tameka , Brennan Mary M. 
Published: September 2022

Background:
Implementation of the Surviving Sepsis Campaign (SSC) guidelines into practice has demonstrated improved outcomes.

Local Problem:
Compliance with a sepsis protocol, based on the SSC guidelines, in an urban teaching hospital was below the national average.

Methods:
A pre- and posttest intervention design was used to improve clinician knowledge, confidence, and compliance with the protocol.

Interventions:
Educational modules were developed on the SSC guidelines and reminder system alerts (RSA) for timely revaluation of patients with sepsis and lactate monitoring were implemented.

Results:
A total of 33 (48%) clinicians participated. There was an increase in knowledge, documentation of sepsis reassessment, and serum lactate monitoring. There was an improvement in clinician perceptions following the initiative.

Conclusions:
The results demonstrate that education, combined with RSAs, can improve protocol knowledge and compliance.