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Biomethane production via biogas upgrading is regarded as a future renewable gas, further boosting the biogas economy. Moreover, when upgrading is realized by the biogas CO2 conversion to CH4 using surplus renewable energy, the process of upgrading becomes a renewable energy storage method. This conversion can be carried out via microorganisms, and has attracted scientific attention, especially under thermophilic conditions. In this study, mesophilic conditions were imposed using a previously developed enriched culture. The enriched culture consisted of the hydrogenotrophic Methanobrevibacter (97% of the Archaea species and 60% of the overall population). Biogas upgrading took place in three lab-scale bioreactors: (a) a 1.2 L bubble reactor (BR), (b) a 2 L trickling bed reactor (TBR) filled with plastic supporting material (TBR-P), and (c) a 1.2 L TBR filled with sintered glass balls (TBR-S). The gas fed into the reactors was a mixture of synthetic biogas and hydrogen, with the H2 to biogas CO2 ratio being 3.7:1, lower than the stoichiometric ratio (4:1). Therefore, the feeding gas mixture did not make it possible for the CH4 content in the biomethane to be more than 97%. The results showed that the BR produced biomethane with a CH4 content of 91.15 ± 1.01% under a gas retention time (GRT) of 12.7 h, while the TBR-P operation resulted in a CH4 content of 90.92 ± 2.15% under a GRT of 6 h. The TBR-S operated at a lower GRT (4 h), yielding an effluent gas richer in CH4 (93.08 ± 0.39%). Lowering the GRT further deteriorated the efficiency but did not influence the metabolic pathway, since no trace of volatile fatty acids was detected. These findings are essential indicators of the process stability under mesophilic conditions.

We conducted a registry analysis including adult acute myeloid leukemia (AML) patients in remission who had received thiotepa, busulfan, and fludarabine (TBF) or treosulfan-based (Treo) conditioning for haplo-hematopoietic stem cell transplant (HSCT) with posttransplant cyclophosphamide (PTCy) between 2010 and 2020. A total of 1123 patients met the inclusion criteria (968 received TBF and 155 received Treo). A 1:1 matched-pair analysis was performed on 142 TBF and 142 Treo patients. In the Treo group, 68% of patients received treosulfan at a dose ≥36 g/m2 and 54% of patients received a second alkylator (thiotepa or melphalan). We observed a trend toward increased incidence of grade II–IV acute (a) graft-versus-host disease (GVHD) at 180 days in the TBF group compared with Treo (29% versus 20%; P = 0.08), while incidence of grade III–IV aGVHD was not statistically different. Similarly, the incidence of chronic (c) GVHD was not statistically different in the 2 groups. Incidence of nonrelapse mortality at 2 years was 19% in TBF and 14% in Treo (P = 0.4). Relapse incidence at 2 years was not statistically different in the 2 groups (16% and 18% in TBF and Treo, respectively; P = 0.9). Leukemia-free survival, overall survival, and GVHD-free, relapse-free survival was 65% versus 68% (P = 0.6), 73% versus 76% (P = 0.5), and 54% versus 53% (P = 0.8) in TBF versus Treo, respectively. In conclusion, we did not find a significant difference between the 2 conditioning in the present study; Treo and TBF represent 2 valid alternative regimens for haplo-HSCT with PTCy for AML in remission.

Regulatory T cells (Tregs) are essential mediators of tolerance mitigating aberrant immune responses. While naturally occurring Treg (nTreg) development and function are directed by epigenetic events, induced Treg (iTreg) identity and mechanisms of action remain elusive. Mirroring the epigenetic circuits of nTregs, we and others have used hypomethylation agents (HAs) to ex vivo convert T cells into iTregs (HA-iTregs) and further showed that the suppressive properties of the HA-iTregs are predominantly confined in an emergent population, which de novo expresses the immunomodulatory molecule HLA-G, consequently providing a surface marker for isolation of the suppressive HA-iTreg compartment (G+ cells). We isolated the HA-induced G+ cells and their G− counterparts and employed high-throughput RNA-sequencing (RNA-seq) analyses to uncover the G+-specific transcriptomic changes guiding T cells toward a regulatory trajectory upon their exposure to HA. We found a distinct transcriptional upregulation of G+ cells accompanied by enrichment of immune-response–related pathways. Although single-cell RNA-seq profiling revealed regulatory G+ cells to have molecular features akin to nTregs, when assessed in conjunction with the comparative transcriptomic analysis and profiling of secreted cytokines against the non-suppressive G− cells, FOXP3 and other T-helper signatures appear to play a minor role in their suppressive phenotype. We found an ectopic expression of IDO-1 and CCL17/22 in G+ cells, denoting that in vitro exposure of T cells to HA may well unlock myeloid suppressor genes. This report provides transcriptional data shaping the molecular identity of a highly purified and potent HA-iTreg population and hints toward ectopic myeloid-specific molecular mechanisms mediating HA-iTreg function.

Abstract Coronary angiography and percutaneous coronary intervention (PCI) procedural details in swine are similar to those performed to humans, since their heart and coronary anatomy closely resembles. However, only a few detailed descriptions of the procedure are available, containing notable differences. We present a feasible and reproducible protocol for percutaneous coronary interventions in porcine experimental models, utilizing ultrasound-guided femoral approach. Nine female pigs were studied to explore the feasibility of superficial femoral arterial (SFA) access for coronary angiography and provisional PCI, as well as the most suitable guiding coronary catheters and angiographic projections for the above interventions. Experiments were performed under general anesthesia, using ultrasound-guided puncture of the SFA to gain arterial access. The Amplatzer AR1® catheter, and the Right Coronary Bypass® catheter were used for the selective engagement of the right and the left coronary artery, respectively. Successful arterial access and subsequent cardiac catheterization were performed in all pigs. Only one animal required a second puncture for femoral artery access. None of the 9 animals presented any significant tachycardia or hypotensive episode. One animal developed an access site-related complication following the first catheterization procedure. During follow-up, 100% success of SFA catheterization was achieved using the same ultrasound-guided technique. The ultrasound-guided superficial femoral artery access for coronary angiography and provisional interventions in porcine models is a quick and safe alternative to the carotid artery approach. The RCB and AR1 catheters may be the best choice for the quick and easy selective coronary engagement of the right and left ostia, respectively.

Regulatory T-cell (Treg) immunotherapy has emerged as a promising and highly effective strategy to combat graft-versus-host disease (GvHD) after allogeneic hematopoietic cell transplantation (allo-HCT). Both naturally occurring Treg and induced Treg populations have been successfully evaluated in trials illustrating the feasibility, safety, and efficacy required for clinical translation. Using a non-mobilized leukapheresis, we have developed a good manufacturing practice (GMP)-compatible induced Treg product, termed iG-Tregs, that is enriched in cells expressing the potent immunosuppressive human leucocyte antigen-G molecule (HLA-G+). To assess the safety and the maximum tolerable dose (MTD) of iG-Tregs, we conduct a phase I–II, two-center, interventional, dose escalation (3 + 3 design), open-label study in adult patients undergoing allo-HCT from an HLA-matched sibling donor, which serves also as the donor for iG-Treg manufacturing. Herein, we present the clinical protocol with a detailed description of the study rationale and design as well as thoroughly explain every step from patient screening, product manufacturing, infusion, and participant follow-up to data collection, management, and analysis (registered EUDRACT-2021-006367-26).

In this registry-based study, we compared outcomes of allogeneic hematopoietic cell transplantation (allo-HCT) in adult patients with acute lymphoblastic leukemia (ALL) transplanted in first complete remission (CR-1), following conditioning with total body irradiation (TBI) at a standard 12-Gray or at a lower 8-Gray total dose. Patients received fludarabine (flu) as the sole chemotherapy complementing TBI. Eight-Gray TBI/flu was used in 494 patients and 12-Gray TBI/flu in 145 patients. Eighty-eight (23.1%) and 36 (29%) of the patients had Ph-negative B-ALL, 222 (58.3%) and 53 (42.7%) had Ph-positive B-ALL, 71 (18.6%) and 35 (28.2%) T-ALL, respectively (P = 0.008). Patients treated with 8-Gray were older than ones received 12-Gray (median 55.7 versus 40.3 years, P < 0.0001) and were more frequently administered in vivo T-cell depletion (71% versus 40%, P

Extant research on knowledge mobilization points to barriers and opportunities for innovation. Edelman et al paper “Academic Health Science Centres as Vehicles for Knowledge Mobilisation in Australia? A Qualitative Study” builds nicely on the existing knowledge base by evaluating the early stages of organisational development of Academic Health Science Centers in Australia. This commentary discusses their research findings by drawing on relevant themes including knowledge mobilization initiatives that have been developed globally to bridge the research-practice gap and knowledge brokering roles for service improvement. Following which, the commentary draws on organizational capabilities literature for knowledge brokering to happen, the latter including the need for measuring implementation fidelity amongst other capabilities. Finally, building on Edelman et al call for more attention to actionoriented roles and knowledge mobilization processes to deliver strategic goals the commentary concludes with a note for collective leadership as an enabler of knowledge mobilization with impact and at scale.

The pre-operative localisation of abnormal parathyroid glands (PG) in parathyroid scintigraphy is essential for suggesting treatment and assisting surgery. Human experts examine the scintigraphic image outputs. An assisting diagnostic framework for localisation reduces the workload of physicians and can serve educational purposes. Former studies from the authors suggested a successful deep learning model, but it produced many false positives. Between 2010 and 2020, 648 participants were enrolled in the Department of Nuclear Medicine of the University Hospital of Patras, Greece. An innovative modification of the well-known VGG19 network (ParaNet+) is proposed to classify scintigraphic images into normal and abnormal classes. The Grad-CAM++ algorithm is applied to localise the abnormal PGs. An external dataset of 100 patients imaged at the same department who underwent parathyroidectomy in 2021 and 2022 was used for evaluation. ParaNet+ agreed with the human readers, showing 0.9861 on a patient-level and 0.8831 on a PG-level basis under a 10-fold cross-validation on the training set of 648 participants. Regarding the external dataset, the experts identified 93 of 100 abnormal patient cases and 99 of 118 surgically excised abnormal PGs. The human-reader false-positive rate (FPR) was 10% on a PG basis. ParaNet+ identified 99/100 abnormal cases and 103/118 PGs, with an 11.2% FPR. The model achieved higher sensitivity on both patient and PG bases than the human reader (99.0% vs. 93% and 87.3% vs. 83.9%, respectively), with comparable FPRs. Deep learning can assist in detecting and localising abnormal PGs in scintigraphic scans of patients with primary hyperparathyroidism and can be adapted to the everyday routine.

Biomethane production via biogas upgrading is regarded as a future renewable gas, further boosting the biogas economy. Moreover, when upgrading is realized by the biogas CO2 conversion to CH4 using surplus renewable energy, the process of upgrading becomes a renewable energy storage method. This conversion can be carried out via microorganisms, and has attracted scientific attention, especially under thermophilic conditions. In this study, mesophilic conditions were imposed using a previously developed enriched culture. The enriched culture consisted of the hydrogenotrophic Methanobrevibacter (97% of the Archaea species and 60% of the overall population). Biogas upgrading took place in three lab-scale bioreactors: (a) a 1.2 L bubble reactor (BR), (b) a 2 L trickling bed reactor (TBR) filled with plastic supporting material (TBR-P), and (c) a 1.2 L TBR filled with sintered glass balls (TBR-S). The gas fed into the reactors was a mixture of synthetic biogas and hydrogen, with the H2 to biogas CO2 ratio being 3.7:1, lower than the stoichiometric ratio (4:1). Therefore, the feeding gas mixture did not make it possible for the CH4 content in the biomethane to be more than 97%. The results showed that the BR produced biomethane with a CH4 content of 91.15 ± 1.01% under a gas retention time (GRT) of 12.7 h, while the TBR-P operation resulted in a CH4 content of 90.92 ± 2.15% under a GRT of 6 h. The TBR-S operated at a lower GRT (4 h), yielding an effluent gas richer in CH4 (93.08 ± 0.39%). Lowering the GRT further deteriorated the efficiency but did not influence the metabolic pathway, since no trace of volatile fatty acids was detected. These findings are essential indicators of the process stability under mesophilic conditions. [ABSTRACT FROM AUTHOR]

Abstract There is a plethora of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) serological tests based either on nucleocapsid phosphoprotein (N), S1-subunit of spike glycoprotein (S1) or receptor binding domain (RBD). Although these single-antigen based tests demonstrate high clinical performance, there is growing evidence regarding their limitations in epidemiological serosurveys. To address this, we developed a Luminex-based multiplex immunoassay that detects total antibodies (IgG/IgM/IgA) against the N, S1 and RBD antigens and used it to compare antibody responses in 1225 blood donors across Greece. Seroprevalence based on single-antigen readouts was strongly influenced by both the antigen type and cut-off value and ranged widely [0.8% (95% CI 0.4–1.5%)–7.5% (95% CI 6.0–8.9%)]. A multi-antigen approach requiring partial agreement between RBD and N or S1 readouts (RBD&N|S1 rule) was less affected by cut-off selection, resulting in robust seroprevalence estimation [0.6% (95% CI 0.3–1.1%)–1.2% (95% CI 0.7–2.0%)] and accurate identification of seroconverted individuals.

Abstract Background Large-scale partnerships between universities and health services are widely seen as vehicles for bridging the evidence–practice gap and for accelerating the adoption of new evidence in healthcare. Recently, different versions of these partnerships – often called academic health science centres – have been established across the globe. Although they differ in structure and processes, all aim to improve the integration of research and education with health services. Collectively, these entities are often referred to as Research Translation Centres (RTCs) and both England and Australia have developed relatively new and funded examples of these collaborative centres. Methods This paper presents findings from a rapid review of RTCs in Australia and England that aimed to identify their structures, leadership, workforce development and strategies for involving communities and service users. The review included published academic and grey literature with a customised search of the Google search engine and RTC websites. Results RTCs are complex system-level interventions that will need to disrupt the current paradigms and silos inherent in healthcare, education and research in order to meet their aims. This will require vision, leadership, collaborations and shared learnings, alongside structures, processes and strategies to deliver impact in the face of complexity. The impact of RTCs in overcoming the deeply entrenched silos across organisations, disciplines and sectors needs to be captured at the systems, organisation and individual levels. This includes workforce capacity and public and patient involvement that are vital to understanding the evolution of RTCs. In addition, new models of leadership are needed to support the brokering and mobilisation of knowledge in complex organisations. Conclusions The development and funding of RTCs represents one of the most significant shifts in the health research landscape and it is imperative that we continue to explore how we can progress the integration of research and healthcare and ensure research meets stakeholder needs and is translated via the collaborations supported by these organisations. Because RTCs are a recent addition to the healthcare landscape in Australia, it is instructive to review the processes and infrastructure needed to support their implementation and applied health research in England.

Abstract Background Over the past decade, Research Translation Centres (RTCs) have been established in many countries. These centres (sometimes referred to as Academic Health Science Centres) are designed to bring universities and healthcare providers together in order to accelerate the generation and translation of new evidence that is responsive to health service and community priorities. This has the potential to effectively ‘flip’ the traditional research and education paradigms because it requires active participation and continuous engagement with stakeholders (especially service users, the community and frontline clinicians). Although investment and expectations of RTCs are high, the literature confirms a need to better understand the processes that RTCs use to mobilise knowledge, build workforce capacity, and co-produce research with patients and the public to ensure population impact and drive healthcare improvement. Methods Semi-structured interviews were conducted with selected leaders and members from select RTCs in England and Australia. Convenience sampling was utilised to identify RTCs, based on their geography, accessibility and availability. Purposive sampling and a snowballing approach were employed to recruit individual participants for interviews, which were conducted face to face or via videoconferencing. Interviews were recorded, transcribed verbatim and analysed using a reflexive and inductive approach. This involved two researchers comparing codes and interrogating themes that were analysed inductively against the study aims and through meetings with the research team. Results A total of 41 participants, 22 from England and 19 from Australia were interviewed. Five major themes emerged, including (1) dissonant metrics, (2) different models of leadership, (3) public and patient involvement and research co-production, (4) workforce development and (5) barriers to collaboration. Conclusions Participants identified the need for performance measures that capture community impact. Better aligned success metrics, enhanced leadership, strategies to partner with patients and the public, enhanced workforce development and strategies to enhance collaboration were all identified as crucial for RTCs to succeed.

Abstract Background Graft-versus-host disease (GVHD) remains a major contributor to mortality and morbidity after allogeneic stem-cell transplantation (allo-HSCT). The updated recommendations suggest that rabbit antithymocyte globulin or anti-T-lymphocyte globulin (ATG) should be used for GVHD prophylaxis in patients undergoing matched-unrelated donor (MUD) allo-HSCT. More recently, using post-transplant cyclophosphamide (PTCY) in the haploidentical setting has resulted in low incidences of both acute (aGVHD) and chronic GVHD (cGVHD). Therefore, the aim of our study was to compare GVHD prophylaxis using either PTCY or ATG in patients with acute myeloid leukemia (AML) who underwent allo-HSCT in first remission (CR1) from a 10/10 HLA-MUD. Methods Overall, 174 and 1452 patients from the EBMT registry receiving PTCY and ATG were included. Cumulative incidence of aGVHD and cGVHD, leukemia-free survival, overall survival, non-relapse mortality, cumulative incidence of relapse, and refined GVHD-free, relapse-free survival were compared between the 2 groups. Propensity score matching was also performed in order to confirm the results of the main analysis Results No statistical difference between the PTCY and ATG groups was observed for the incidence of grade II–IV aGVHD. The same held true for the incidence of cGVHD and for extensive cGVHD. In univariate and multivariate analyses, no statistical differences were observed for all other transplant outcomes. These results were also confirmed using matched-pair analysis. Conclusion These results highlight that, in the10/10 HLA-MUD setting, the use of PTCY for GVHD prophylaxis may provide similar outcomes to those obtained with ATG in patients with AML in CR1.