Impact of lower concentrations of dimethyl sulfoxide on cryopreservation of autologous hematopoietic stem cells: a systematic review and meta-analysis of controlled clinical studies.

BACKGROUND AIMS: Cryopreservation of hematopoietic stem cells (HSCs) is crucial for autologous transplantation, cord blood banking and other special circumstances. Dimethyl sulfoxide (DMSO) is used most commonly for cryopreserving HSC products but can cause infusional toxicities and affect cell viability and engraftment after transplant. A systematic review of controlled studies using lower concentrations of DMSO to cryopreserve HSC products in clinical transplant studies is needed to determine the effect of reducing DMSO concentrations on post-thaw cell viability, initial engraftment and adverse effects on patient health. METHODS: All studies identified in our systematic search (to July 11, 2023) examining the use of cryopreserved peripheral blood stem cells (PBSCs) for autologous stem cell transplantation (AHCT) were included. Meta-analysis was performed to determine how varying the concentration of DMSO during cryopreservation effects post-thaw cell viability, initial engraftment and adverse effects on patient health. RESULTS: A total of 1547 studies were identified in our systematic search, with seven published articles meeting eligibility for inclusion in meta-analysis. All patients underwent AHCT using (PBSCs) to treat hematologic malignancies. The viability of CD34+ cells post thaw was greater when cryopreserved with 5% DMSO compared with 10% DMSO, with lower rates of adverse side effects in patients. DMSO concentration had minimal impact on rates of initial engraftment. Significant heterogeneity in outcome reporting was observed and the potential for bias was identified in all studies. CONCLUSIONS: Reducing the concentration of DMSO from 10% to 5% during cryopreservation of autologous PBSCs may improve cell viability and reduce DMSO-associated adverse effects in patients undergoing AHCT. Data from more studies with similar patients and standard outcome reporting are needed to increase confidence in our initial observations. PROTOCOL REGISTRATION: PROSPERO; registration number CRD42023476809 registered November 8, 2023.

Determining the impact of current Canadian stem cell registry policy on donor availability via dynamic registry simulation.

BACKGROUND AND OBJECTIVES: When a haematopoietic stem cell registry size is constrained by limits on recruiting, as in Canada, identifying the right person to recruit is a critical determinant of effectiveness. The aim of this study was to evaluate the impact of changes to donor recruitment effort, within ethnic groups, on the matching effectiveness of the Canadian registry as it evolves over time. MATERIALS AND METHODS: Simulation methods are applied to create a cohort of donor recruits and patients over a 10-year time horizon. New recruits are added to the registry each year, while some existing donors 'age-out' upon reaching their 36th birthday. In a similar fashion, simulated patient lists are created. At the end of each simulated year, simulated patients are matched against the simulated registry. RESULTS: There are increased matches in non-White populations when diverse registrants are preferentially recruited, but there are larger decreases in the number of matches for Caucasian patients. Additionally, ethnic communities that have limited registrants in the Canadian registry in 2021 do not benefit from increased recruiting efforts as much as communities with a larger initial number of registrants. CONCLUSION: Preferentially recruiting from non-Caucasian populations reduces the number of matches from Canadian sources because increases in non-Caucasian populations will not fully counterbalance decreases to Caucasian patient matches. Nevertheless, more than 80% of all matches are for Caucasian patients, regardless of the donor recruiting effort within ethnic groups.

Outcomes with low dose anti-thymocyte globulin based graft versus host disease prophylaxis after mismatched unrelated donor allogeneic hematopoietic cell transplantation.

BACKGROUND: Anti-thymocyte globulin (ATG) based graft versus host disease (GVHD) prophylaxis is widely used for mismatched unrelated donor allogeneic hematopoietic cell transplantation (HCT) although optimal dose remains unclear. Although recent literature suggested improved outcomes with PTCy-based regimens when compared to ATG-based regimens these studies used doses of ATG ≥5 mg/kg. Thus, we analyzed outcomes of HLA 9/10 MMUD allogeneic HCTs using lower-dose ATG-based regimens at our center. METHODS: We retrospectively analyzed outcomes of HLA 9/10 MMUD allogeneic HCTs using lower dose ATG-based regimens for all adults undergoing allogeneic HCT at The Ottawa Hospital from 2015 to 2022. Data regarding demographics, conditioning regimen, dose of ATG, rates of GVHD, duration of remission, and survival, were collected and analyzed. RESULTS: Seventy-seven (n = 77) patients (males 62.3%; median age 50 years) underwent allogeneic HCT from MMUD. Majority(81%; n = 63) received 2.5 mg/kg of rabbit ATG and remaining 18.2% (n = 14) received 4.5 mg/kg. Grade II-IV acute GVHD occurred in 24.7% (n = 19) while any chronic GVHD occurred in 32.5% (n = 25) patients. After a median follow-up of 21 months, relapse occurred in 28.6% of patients. Two-year OS, GRFS, CIR, and NRM were 60.6%, 45.3%, 16.9%, and 18.2% respectively. Dose of ATG (2.5 mg/kg vs. 4.5 mg/kg) was not associated with outcomes in either univariate or multivariate analyses. CONCLUSIONS: When compared to published studies using ATG doses ≥5 mg/kg, GVHD prophylaxis using lower dose ATG may potentially lead to improved outcomes in patients undergoing MMUD allogeneic HCT. Further studies are needed to directly compare lower dose ATG to PTCy-based regimens to determine ideal GVHD prophylaxis for these patients.

Identification of Partial Discharge Sources by Feature Extraction from a Signal Conditioning System.

This paper addresses the critical challenge of detecting, separating, and classifying partial discharges in substations. It proposes two solutions: the first involves developing a signal conditioning system to reduce the sampling requirements for PD detection and increase the signal-to-noise ratio. The second approach uses machine learning techniques to separate and classify PD based on features extracted from the conditioned signal. Three clustering algorithms (K-means, Gaussian Mixture Model (GMM), and Mean-shift) and the Support Vector Machine (SVM) method were used for signal separation and classification. The proposed system effectively reduced high-frequency components up to 50 MHz, improved the signal-to-noise ratio, and effectively separated different sources of partial discharges without losing relevant information. An accuracy of up to 93% was achieved in classifying the partial discharge sources. The successful implementation of the signal conditioning system and the machine learning-based signal separation approach opens avenues for more economical, scalable, and reliable PD monitoring systems.

Exploring crystal structure-physical property relationships with pressure.

From its conception, X-ray crystallography has provided a unique understanding of the structure, bonding and electronic state of materials, which, in turn, unlocks a means of examining the properties and function of crystalline systems. Using state-of-the-art single-crystal X-ray diffraction, along with UV-Vis spectroscopy and DFT calculations, Zwolenik et al. [(2024). IUCrJ, 11, 519-527] have provided a comprehensive study of the structure-optical property relationship of 1,3-diacetylpyrene with methodologies that are increasingly accessible to non-specialist laboratories.

Negative linear compressibility exhibited by the hybrid perovskite [(NH2)3C]Er(HCO2)2(C2O4).

Extended framework materials with specific topologies can exhibit unusual mechanical behaviour, such as expanding in one direction under hydrostatic (uniform) pressure, known as negative linear compressibility (NLC). Here, two hybrid perovskite frameworks with winerack structures, a known NLC topology, are investigated under pressure. [C(NH2)3]Er(HCO2)2(C2O4) exhibits NLC from ambient pressure to 2.63(10) GPa and is the first reported NLC hybrid perovskite from ambient pressure. However, isostructural [(CH3)2NH2]Er(HCO2)2(C2O4) instead compresses relatively moderately along all axes before it undergoes a phase transition above 0.37(10) GPa. The differences in the mechanical properties can be interpreted from differences in host-guest interactions within these frameworks, primarily their hydrogen bond networks.

Homing and Engraftment of Hematopoietic Stem Cells Following Transplantation: A Pre-Clinical Perspective.

Hematopoietic stem-cell (HSC) transplantation (HSCT) is used to treat various hematologic disorders. Use of genetically modified mouse models of hematopoietic cell transplantation has been critical in our fundamental understanding of HSC biology and in developing approaches for human patients. Pre-clinical studies in animal models provide insight into the journey of transplanted HSCs from infusion to engraftment in bone-marrow (BM) niches. Various signaling molecules and growth factors secreted by HSCs and the niche microenvironment play critical roles in homing and engraftment of the transplanted cells. The sustained equilibrium of these chemical and biologic factors ensures that engrafted HSCs generate healthy and durable hematopoiesis. Transplanted healthy HSCs compete with residual host cells to repopulate stem-cell niches in the marrow. Stem-cell niches, in particular, can be altered by the effects of previous treatments, aging, and the paracrine effects of leukemic cells, which create inhospitable bone-marrow niches that are unfavorable for healthy hematopoiesis. More work to understand how stem-cell niches can be restored to favor normal hematopoiesis may be key to reducing leukemic relapses following transplant.

Optimizing Access to Unrelated Donors in Canada: Re-Examining the Importance of Donor Factors on Outcomes Following Hematopoietic Cell Transplantation.

HLA-matched allogeneic hematopoietic cell transplantation (HCT) is a curative therapy for many patients. Unrelated HLA-matched donors are the most frequently used donor for HCT. When more than one donor transplant option is available, transplant centers can select donors based on non-HLA factors. With improved ability to prevent and treat immune complications, such as graft-versus-host disease and infections, it may be possible to proceed more often using HLA-mismatched donors, allowing greater consideration of non-HLA factors, such as donor age, CMV serostatus, and ABO blood group matching, which have demonstrated important impacts on transplant outcomes. Additional factors to consider are donor availability rates and the usage of domestic donors to optimize outcomes. A review of non-HLA factors and considerations on the selection of optimal unrelated donors for HCT are provided within this updated current context.

Head Exposure to Acceleration Database in Sport (HEADSport): a kinematic signal processing method to enable instrumented mouthguard (iMG) field-based inter-study comparisons.

Objective: Instrumented mouthguard (iMG) systems use different signal processing approaches limiting field-based inter-study comparisons, especially when artefacts are present in the signal. The objective of this study was to assess the frequency content and characteristics of head kinematic signals from head impact reconstruction laboratory and field-based environments to develop an artefact attenuation filtering method (HEADSport filter method). Methods: Laboratory impacts (n=72) on a test-dummy headform ranging from 25 to 150 g were conducted and 126 rugby union players were equipped with iMGs for 209 player-matches. Power spectral density (PSD) characteristics of the laboratory impacts and on-field head acceleration events (HAEs) (n=5694) such as the 95th percentile cumulative sum PSD frequency were used to develop the HEADSport method. The HEADSport filter method was compared with two other common filtering approaches (Butterworth-200Hz and CFC180 filter) through signal-to-noise ratio (SNR) and mixed linear effects models for laboratory and on-field events, respectively. Results: The HEADSport filter method produced marginally higher SNR than the Butterworth-200Hz and CFC180 filter and on-field peak linear acceleration (PLA) and peak angular acceleration (PAA) values within the magnitude range tested in the laboratory. Median PLA and PAA (and outlier values) were higher for the CFC180 filter than the Butterworth-200Hz and HEADSport filter method (p<0.01). Conclusion: The HEADSport filter method could enable iMG field-based inter-study comparisons and is openly available at https://github.com/GTBiomech/HEADSport-Filter-Method.

The Incidence and Propensity of Head Acceleration Events in a Season of Men's and Women's English Elite-Level Club Rugby Union Matches.

OBJECTIVES: To describe and compare the incidence and propensity of head acceleration events (HAEs) using instrumented mouthguards (iMG) by playing position in a season of English elite-level men's and women's rugby union matches. METHODS: iMG data were collected for 255 men and 133 women from 1,865 and 807 player-matches, respectively, and synchronised to video-coded match footage. Head peak resultant linear acceleration (PLA) and peak resultant angular acceleration (PAA) were extracted from each HAE. Mean incidence and propensity values were calculated across different recording thresholds for forwards and backs in addition to positional groups (front row, second row, back row, half backs, centres, back three) with 95% confidence intervals (CI) estimated. Significance was determined based on 95% CI not overlapping across recording thresholds. RESULTS: For both men and women, HAE incidence was twice as high for forwards than backs across the majority of recording thresholds. HAE incidence and propensity were significantly lower in the women's game compared to the men's game. Back-row and front-row players had the highest incidence across all HAE thresholds for men's forwards, while women's forward positional groups and men's and women's back positional groups were similar. Tackles and carries exhibited a greater propensity to result in HAE for forward positional groups and the back three in the men's game, and back row in the women's game. CONCLUSION: These data offer valuable benchmark and comparative data for future research, HAE mitigation strategies, and management of HAE exposure in elite rugby players. Positional-specific differences in HAE incidence and propensity should be considered in future mitigation strategies.

Embracing the impact from instrumented mouthguards (iMGs): A survey of iMG managers' perceptions of staff and player interest into the technology, data and barriers to use.

Instrumented mouthguards (iMGs) are a novel technology being used within rugby to quantify head acceleration events. Understanding practitioners' perceptions of the barriers and facilitators to their use is important to support implementation and adoption. This study assessed men's and women's rugby union and league iMG managers' perceptions of staff and player interest in the technology, data and barriers to use. Forty-six iMG managers (men's rugby union and league n = 20 and n = 9 and women's rugby union and league n = 7 and n = 10) completed an 18-question survey. Perceived interest in data varied across staff roles with medical staff being reported as having the most interest. The iMG devices were perceived as easy to use but uncomfortable. Several uses of data were identified, including medical applications, player monitoring and player welfare. The comfort, size and fit of the iMG were reported as the major barriers to player use. Time constraints and a lack of understanding of data were barriers to engagement with the data. Continued education on how iMG data can be used is required to increase player and staff buy-in, alongside improving comfort of the devices. Studies undertaken with iMGs investigating player performance and welfare outcomes will make data more useful and increase engagement.

Cell Therapy Transplant Canada (CTTC) Consensus-Based Guideline 2024 for Management and Treatment of Chronic Graft-Versus-Host Disease and Future Directions for Development.

This is a consensus-based Canadian guideline whose primary purpose is to standardize and facilitate the management of chronic graft-versus-host disease (cGvHD) across the country. Creating uniform healthcare guidance in Canada is a challenge for a number of reasons including the differences in healthcare authority structure, funding and access to healthcare resources between provinces and territories, as well as the geographic size. These differences can lead to variable and unequal access to effective therapies for GvHD. This document will provide comprehensive and practical guidance that can be applied across Canada by healthcare professionals caring for patients with cGvHD. Hopefully, this guideline, based on input from GvHD treaters across the country, will aid in standardizing cGvHD care and facilitate access to much-needed novel therapies. This consensus paper aims to discuss the optimal approach to the initial assessment of cGvHD, review the severity scoring and global grading system, discuss systemic and topical treatments, as well as supportive therapies, and propose a therapeutic algorithm for frontline and subsequent lines of cGvHD treatment in adults and pediatric patients. Finally, we will make suggestions about the future direction of cGvHD treatment development such as (1) a mode-of-action-based cGvHD drug selection, according to the pathogenesis of cGvHD, (2) a combination strategy with the introduction of newer targeted drugs, (3) a steroid-free regimen, particularly for front line therapy for cGvHD treatment, and (4) a pre-emptive approach which can prevent the progression of cGvHD in high-risk patients destined to develop severe and highly morbid forms of cGvHD.

The bii4africa dataset of faunal and floral population intactness estimates across Africa's major land uses.

Sub-Saharan Africa is under-represented in global biodiversity datasets, particularly regarding the impact of land use on species' population abundances. Drawing on recent advances in expert elicitation to ensure data consistency, 200 experts were convened using a modified-Delphi process to estimate 'intactness scores': the remaining proportion of an 'intact' reference population of a species group in a particular land use, on a scale from 0 (no remaining individuals) to 1 (same abundance as the reference) and, in rare cases, to 2 (populations that thrive in human-modified landscapes). The resulting bii4africa dataset contains intactness scores representing terrestrial vertebrates (tetrapods: ±5,400 amphibians, reptiles, birds, mammals) and vascular plants (±45,000 forbs, graminoids, trees, shrubs) in sub-Saharan Africa across the region's major land uses (urban, cropland, rangeland, plantation, protected, etc.) and intensities (e.g., large-scale vs smallholder cropland). This dataset was co-produced as part of the Biodiversity Intactness Index for Africa Project. Additional uses include assessing ecosystem condition; rectifying geographic/taxonomic biases in global biodiversity indicators and maps; and informing the Red List of Ecosystems.