Conditioning Protocol Research Articles

Mechanisms of Stabilization and Degradation of Transition Metal Oxygen Electroreduction Catalysts with in-Situ Electrochemical Flow Cell ICP-MS

Proton exchange membrane hydrogen fuel cell (PEMFC) deployment is presently limited by the high material cost of oxygen reduction reaction (ORR) electrocatalysts at the cathode. Developing low-cost, earth-abundant alternatives for use in acidic environments presents a material stability challenge, especially for long-term device operation. Platinum (Pt)-based materials are used in typical commercial PEMFC cathode formulations due to their simultaneous high performance and long-term stability despite the prohibitively high material cost. Developing lower-cost, longer-life catalyst materials based on earth abundant transition metals can accelerate the adoption of PEMFC technology. The impact of potential, current density, and local microenvironment has been shown to cause degradation of non-Pt materials but standard ex situ measurements can only probe surface restructuring and cumulative dissolution after operation. Material-specific degradation mechanisms that are strong functions of the operating conditions cannot be ascertained without in situ quantification of material degradation under PEMFC-relevant conditions. Information about the degradation pathways of these non-precious catalysts can assist with material design for devices; however, most efforts towards developing an in-situ understanding of PEMFC cathode catalyst degradation under operating conditions are generally limited to Pt-based materials. Extensive in situ characterization has revealed Pt-specific mechanistic information about corrosion pathways as well as conditions that exacerbate Pt alloy leaching. It has been hypothesized that the Pt degradation processes are related to oxide formation under potential cycling. With this critical in-situ information, Pt conditioning protocols have been developed to enhance material lifetime; however, investigations on non-precious materials are less common. Insights into non-precious catalyst degradation in PEMFC operating conditions are not as well-established but could be essential in enabling low-cost materials for commercial use. There is a need for more insights into a vast array of materials which necessitates the development of faster, preferably benchtop techniques for degradation analysis.In this work, we use an in situ electrochemical flow cell assembly and coupled it with an inductively coupled plasma-mass spectrometer (ICP-MS) to quantify the loss of material in real time for several non-Pt materials under reaction conditions. The flow cell is fed by a peristaltic pump at 2.5 mL/min of gas-saturated acidic electrolyte for optimal mass transport. The cell has a three-electrode configuration with a compression-mounted metal foil working electrode, silver/silver chloride reference electrode, and Pt counter electrode downstream of other components. We evaluate a variety of transition metals across the spectrum of ORR activity: palladium, silver, nickel, copper, manganese, and cobalt. Each metal is tested under oxygen and nitrogen saturation in five electrolytes of identical pH: perchloric acid, sulfuric acid, nitric acid, hydrochloric acid, and hydrobromic acid. This setup allows for nearly real time measurement of ORR kinetics and in situ element-specific dissolution rates as a function of time. With careful design of experimental conditions and controlled variables, we are able to suggest mechanisms of degradation with specific reference to conditions under which material loss occurred such as high/low potential, oxygen-saturated/nitrogen-saturated electrolyte, or faradaic/non-faradaic current. We find some metals are stable under nitrogen-saturated electrolyte but corrode more under oxygen-saturated electrolyte only while ORR active. Furthermore, other metals are stable in nitrogen saturated electrolyte at all tested electrochemical conditions but unstable under oxygen saturated electrolyte but only outside the ORR range, implying that cathodic faradaic processes might be stabilizing the surface at low potentials. This stabilization where a thermodynamically unstable material (based on its Pourbaix diagram) exhibits greater immunity while performing ORR in certain electrolytes could inform the development stability mechanisms that direct the design of next generation, non-precious PEMFC cathode catalyst materials. With combined in situ catalyst stability analysis in five pH 1 electrolytes, we can recommend specific conditions for optimizing activity and stability based on the potential range of operation and the electrolyte composition/saturation. We can also distill mechanistic insights from these experiments by creating models that validate causes of catalyst degradation. These models are built using “graphical causal modeling”, which is a mathematical field that goes beyond correlative predictions by venturing into causal inference. We hope to expand this framework into other electrocatalytic reactions of interest. The in-situ ICP-MS electrochemical flow cell setup exhibits promise for accelerating materials stability analysis for enabling next generation Pt-free ORR electrocatalysts through practical experiments and direct comparability to established electrochemical techniques.

Electro-Acupuncture Effects Measured by Functional Magnetic Resonance Imaging-A Systematic Review of Randomized Clinical Trials.

Electro-acupuncture, an innovative adaptation of traditional acupuncture, combines electrical stimulation with acupuncture needles to enhance therapeutic effects. While acupuncture is widely used, its biological mechanisms remain incompletely understood. Recent research has explored the neurophysiological aspects of acupuncture, particularly through functional magnetic resonance imaging (fMRI) to investigate its effects on brain activity. In this systematic review, we conducted an extensive search for randomized clinical trials examining electro-acupuncture effects measured by fMRI. We employed strict eligibility criteria, quality assessment, and data extraction. Five studies met our inclusion criteria and were analyzed. The selected studies investigated electro-acupuncture in various medical conditions, including carpal tunnel syndrome, fibromyalgia, Crohn's disease, irritable bowel syndrome, and obesity. Notably, electro-acupuncture was found to modulate brain activity and connectivity in regions associated with pain perception, emotional regulation, and cognitive processing. These findings align with the holistic approach of traditional Chinese medicine, emphasizing the interconnectedness of body and mind. In carpal tunnel syndrome, electro-acupuncture at both local and distal sites showed neurophysiological improvements, suggesting distinct neuroplasticity mechanisms. In fibromyalgia, somatosensory electro-acupuncture correlated with reduced pain severity, enhanced brain connectivity, and increased gamma-aminobutyric acid levels. For Crohn's disease, electro-acupuncture influenced the homeostatic afferent processing network, potentially mitigating gut inflammation. Electro-acupuncture for irritable bowel syndrome led to decreased activity in the anterior cingulate cortex, offering pain relief, while electro-acupuncture for obesity impacted brain regions associated with dietary inhibition and emotional regulation. This systematic review provides evidence that electro-acupuncture can positively impact a range of medical conditions, possibly by modulating brain activity and connectivity. While the quality of the reviewed studies is generally good, further research with larger sample sizes and longer-term assessments is needed to better understand the mechanisms and optimize electro-acupuncture protocols for specific health conditions. The limited number of studies in this review emphasizes the need for broader investigations in this promising field. The research protocol was registered in PROSPERO (CRD42023465866).

Tight-binding model subject to conditional resets at random times.

We investigate the dynamics of a quantum system subjected to a time-dependent and conditional resetting protocol. Namely, we ask what happens when the unitary evolution of the system is repeatedly interrupted at random time instants with an instantaneous reset to a specified set of reset configurations taking place with a probability that depends on the current configuration of the system at the instant of reset? Analyzing the protocol in the framework of the so-called tight-binding model describing the hopping of a quantum particle to nearest-neighbor sites in a one-dimensional open lattice, we obtain analytical results for the probability of finding the particle on the different sites of the lattice. We explore a variety of dynamical scenarios, including the one in which the resetting time intervals are sampled from an exponential as well as from a power-law distribution, and a setup that includes a Floquet-type Hamiltonian involving an external periodic forcing. Under exponential resetting, and in both the presence and absence of the external forcing, the system relaxes to a stationary state characterized by localization of the particle around the reset sites. The choice of the reset sites plays a defining role in dictating the relative probability of finding the particle at the reset sites as well as in determining the overall spatial profile of the site-occupation probability. Indeed, a simple choice can be engineered that makes the spatial profile highly asymmetric even when the bare dynamics does not involve the effect of any bias. Furthermore, analyzing the case of power-law resetting serves to demonstrate that the attainment of the stationary state in this quantum problem is not always evident and depends crucially on whether the distribution of reset time intervals has a finite or an infinite mean.

Body composition profile of Brazilian national circus school students

Problem Statement. Professional education in circus has been increasing worldwide, placing the training programmes at the center of circus debate. Purpose. Concerning the physical demands of circus students, this research describes the body composition of Brazilian National Circus School students. Approach. Skinfold analyses was used to estimate body fat (%), fat free mass (kg) and body mass index (kg/m-2) in 57 students (n= 30 men, n= 27 women). Results. Men presented higher body weight, height, fat free mass (men 67.2 ± 7.0 kg and 45.7 ± 4.7 kg and for women), body mass index (men 24.1 ±1.6 kg/m2 and women 21.4 ± 2.0 kg/m2) and lower body fat (%) compared to women (men 7.2 ± 3.7 % and women 16.3 ± 3.7). The reassessment showed no differences in body composition for both sexes, a large heterogeneity of interindividual responses was observed (-3.9 to 4.0 for women; -1.5 to 6,5 men). Conclusions. The body fat and body mass index are similar to high performance athletes. No difference was observed between the assessments. The interindividual response to training showed no effect on body fat. However, the interindividual heterogeneity responses suggest adjustments of physical conditioning protocol in order to optimize the responses individually. The 7 or 3 skinfold protocol did not differ on the outcomes. Body composition of circus students’ needs to take into account the circus disciplines, age and biological diversity, and it is a key aspect to monitor training to avoid unsafe situations or unhealthy status. Keywords: performing arts; anthropometry; body mass; physical training.

Comparison of fludarabine/melphalan (FluMel) with fludarabine/melphalan/BCNU or thiotepa (FBM/FTM) in patients with AML in first complete remission undergoing allogeneic hematopoietic stem cell transplantation - a registry study on behalf of the EBMT Acute Leukemia Working Party.

Conditioning protocols for patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT) are being developed continuously to improve their anti-leukemic efficacy and reduce their toxicity. In this study, we compared the conditioning protocol of fludarabine with melphalan 140 mg/m2 (FluMel) with conditioning protocols based on this same backbone but with an additional alkylating agent i.e., either fludarabine/BCNU (also known as carmustine)/melphalan (FBM), or fludarabine/thiotepa/melphalan (FTM) 110 mg/m2. We included 1272 adult patients (FluMel, n = 1002; FBM/FTM, n = 270) with acute myeloid leukemia (AML) with intermediate/poor cytogenetic risk in first complete remission (CR) from the registry of the EBMT Acute Leukemia Working Party. Despite patients in the FBM/FTM group were older (64.1 years vs. 59.8 years, p < 0.001) and had a worse Karnofsky performance score (KPS < 90, 33% vs. 24%, p = 0.003), they showed a better overall survival (OS) (2 y OS: 68.3% vs. 58.1%, p = 0.02) and less non-relapse mortality (NRM) (2 y NRM: 15.8% vs. 22.2%, p = 0.009) compared to patients treated with FluMel. No significant differences were observed in relapse incidence (RI) (2 y RI: 24.9% vs. 23.7%, p = 0.62). In conclusion, the addition of a second alkylating agent (BCNU/carmustine or thiotepa) to FluMel as FBM/FTM conditioning, improves OS in AML patients in first CR with intermediate/poor risk cytogenetics after allo-HCT.

Stimulating oxytocin receptors in the basolateral amygdala enhances stimulus processing: Differential and consistent effects for stimuli paired with fear versus sucrose in extinction and reversal learning

Oxytocin (OT) influences a range of social behaviors by enhancing the salience of social cues and regulating the expression of specific social behaviors (e.g., maternal care versus defensive aggression). We previously showed that stimulating OT receptors in the basolateral amygdala of rats also enhanced the salience of fear conditioned stimuli: relative to rats given vehicle infusions, rats infused with [Thr4,Gly7]-oxytocin (TGOT), a selective OT receptor agonist, showed greater discrimination between a cue predictive of danger, and one that signaled safety. In the present series of experiments using male rats, the effects of OT receptor activation in the basolateral amygdala on stimulus processing were examined further using conditioning protocols that consist of changes in stimulus-outcome contingencies (i.e., extinction and reversal), and with stimuli paired with aversive (i.e., foot shock) and appetitive (i.e., sucrose) outcomes. It was revealed that the effects of OTR stimulation diverge for aversive and appetitive learning – enhancing the former but not the latter. However, across both types of learning, OTR stimulation enhanced the detection of conditioned stimuli. Overall, these results are consistent with an emerging view of OT’s effects on stimulus salience; facilitating the detection of meaningful stimuli while reducing responding to those that are irrelevant.

MICROTENSILE BOND STRENGTH OF UNIVERSAL ADHESIVE TO DENTIN AFTER ER: YAG LASER PRETREATMENT WITH DIFFERENT CONDITIONING MODES - AN IN VITRO STUDY

Adhesion to dentin remains challenging due to its complex nature that prevents complete infiltration of hydrophobic monomer to hydrophilic dentinal substrate. Recently, Er:YAG laser has been used in dentin pretreatment to enhance the bond strength. A deficient hybrid layer is formed following laser etching as it causes thermal damage and collagen denaturation of dentinal substrate. As the results are controversial, attempts are made to modify laser etching technique with respect to energy density, pulse duration and water spray. Thus, the present study aimed to evaluate the influence of Er:YAG laser conditioning of dentin by activation of Chlorhexidine collagen stabilising agent on the bond strength. Samples included 60 freshly extracted premolar which were divided into three groups (n=20) based on the protocol of dentin pretreatment done: Group 1 (Control) - Phosphoric acid etching followed by universal adhesive; Group 2 (Experimental) - Conventional Er:YAG laser dentioning; Group3 (Experimental) - Er:YAG laser dentin conditioning with coronal reservoir of 0.12% Chlorhexidine. Occlusal class 1 cavity was prepared on the samples followed by which dentin conditioning protocol was carried out for the respective groups. Universal adhesive was applied followed by Composite resin restoration. 1000 cycles of Thermocycling was done and the samples were sectioned to obtain microsections. Microtensile bond strength values were obtained by subjecting the specimens to Universal testing machine.Highest microtensile bond strength value was obtained for group 1 followed by group 3 with least value obtained for Group2 with statistically significant values between the groups. (p&lt;0.0001). Within the limitations of the present invitro study, it can be concluded that preetching with phosphoric acid increases the bond strength of universal adhesive to dentin. Laser conditioning of dentin through activation of chlorhexidine provided better bond strength value of universal adhesive when compared to conventional laser dentin conditioning.

Allogeneic Hematopoietic Stem Cell Transplantation with Treosulfan -Fludarabine and Busulfan-Fludarabine Conditioning Have Similar Efficacy in Patients ≥65 Years Old or Those with Comorbidities

Background: Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially curative treatment for hematological malignancies. Myeloablative conditioning (MAC) results in a better disease-free survival (DFS) compared to reduced-intensity conditioning (RIC). However, the use of MAC in older adults or in those with comorbidities is limited due to a high rate of non-relapse mortality (NRM). Treosulfan-based conditioning regimens were found to result in superior DFS compared to RIC, without increased NRM. However, patients over the age of 65 were less represented in trials assessing the safety and efficacy of treosulfan-based conditioning relative to MAC. In recent years, fludarabine-treosulfan (FT) conditioning was used at Rambam for patients ≥65 years old, or for those with an HCT - comorbidity index (HCT-CI) score &amp;gt;2. This study aimed to evaluate the efficacy of the FT conditioning protocol and fludarabine-busulfan for 4 days (FB4) in older adults or in those with comorbidities. Methods: This single-center retrospective study included the following 3 groups: 1) patients who received the FT protocol; 2) patients aged &amp;lt;65 years with HCT-CI ≤2, who received the FB4 protocol; 3) patients aged ≥65 and/or with HCT-CI &amp;gt;2, who received the FB4 protocol. The results of patients included in group 2 were used as a reference. Data were retrieved from the electronic medical records. Baseline characteristics, transplant outcomes and complications were compared. Categorical variables and non-parametric variables were evaluated with the Fisher's exact test and Mann-Whitney U test, respectively. Results: One hundred and ninety patients were analyzed. All underwent HSCT between January 2015 and December 2021 (table 1). The FT group, younger and older FB4 groups included 57, 61 and 72 patients, respectively. Patient median age was 65 years in both the FT and older FB4 groups, compared to 58 in the younger FB4 group (p&amp;lt;0.05). Patients in the FT group had significantly more comorbidities compared to younger FB4 (p&amp;lt;0.001) and older FB4 groups (p=0.005), with a median HCT-CI of 4, 0 and 3, respectively. During a median follow-up of 48.8 months, there were no significant differences between the groups in terms of the incidence of acute graft-versus-host disease (GVHD), disease relapse, NRM or overall survival (table 2). However, the chronic GVHD rate was 34.4% in the younger FB4 group and only 15.8% in the FT group (p=0.035). This rate was 25% in the older FB4 group (p=NS). Mucositis rate was significantly lower in the FT group, with 31.6% of patients being mucositis-free, compared to 6.6% and 13.9% in the younger and older FB4 groups, respectively. However, the rate of bacteremia events was significantly increased in the FT group (49.1%) relative to the younger FB4 (13.1%) and the older FB4 (23.6%) groups. Conclusions: In older patients or in those with comorbidities, FT appears to be as efficient as FB4 conditioning. Furthermore, these outcomes are comparable to those observed in younger patients conditioned with FB4. Hence, both of the evaluated regimens could be considered in these patient populations. Prospective randomized studies are warranted to further evaluate these findings.

Long-term prognosis of fatty-acid oxidation disorders in adults: Optimism despite the limited effective therapies available.

Fatty-acid oxidation disorders (FAODs) are recessive genetic diseases. We report here clinical and paraclinical data from a retrospective study of 44 adults with muscular FAODs from six French reference centers for neuromuscular or metabolic diseases. The study cohort consisted of 44 adult patients: 14 with carnitine palmitoyl transferase 2 deficiency (32%), nine with multiple acyl-CoA deficiency (20%), 13 with very long-chain acyl-CoA dehydrogenase deficiency (30%), three with long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (7%), and five with short-chain acyl-CoA dehydrogenase deficiency (11%). Disease onset occurred during childhood in the majority of patients (59%), with a mean age at onset of 15 years (range = 0.5-35) and a mean of 12.6 years (range = 0-58) from disease onset to diagnosis. The principal symptoms were acute muscle manifestations (rhabdomyolysis, exercise intolerance, myalgia), sometimes associated with permanent muscle weakness. Episodes of rhabdomyolysis were frequent (84%), with a mean creatinine kinase level of 68,958 U/L (range = 660-300,000). General metabolic complications were observed in 58% of patients, respiratory manifestations in 18% of cases, and cardiological manifestations in 9% of cases. Fasting acylcarnitine profile was used to orient genetic explorations in 65% of cases. After a mean follow-up of 10 years, 33% of patients were asymptomatic and 56% continued to display symptoms after exercise. The frequency of rhabdomyolysis decreased after diagnosis in 64% of cases. A standardized register would complete this cohort description of muscular forms of FAODs with exhaustive data, making it possible to assess the efficacy of therapeutic protocols in real-life conditions and during the long-term follow-up of patients.

The impact of covid-19 pandemic on pregnancy outcome

BackgroundThe acute respiratory disease caused by the coronavirus (COVID-19) has spread rapidly worldwide yet has not been eliminated. The infection is especially deadly in vulnerable populations. The current studies indicate that pregnant women are at greater risk of getting seriously ill. Even though fetuses protect against disease, the additional finding showed that the COVID-19 pandemic could increase fetal and maternal morbidities. In a situation where COVID-19 and new strains of the virus are still not controlled, scientists predicted that the world might experience another pandemic. Consequently, more research about the effects of COVID-19 infection on pregnancy outcomes is needed. This study aimed to compare the pregnancy outcomes of Iranian pregnant women in the first year of the pandemic with the previous year.MethodsThis prospective cross-sectional study was performed to compare the pregnancy outcome during the COVID-19 pandemic among Iranian pregnant women who gave birth during the pandemic and one year before the pandemic (2019–2020 and 2020–2021). The sample size was 2,371,332 births registered at hospitals and birth centers platforms. The studied variables include stillbirth, congenital anomaly, birth weight, preeclampsia, gestational diabetes, cesarean section, ICU admission, mean of the gestational age at birth, preterm births, NICU admission, neonatal mortality and the percentage of deliveries with at least one complication such as blood transfusion and postpartum ICU admission. Analyzing data was done by using SPSS version 25 software.ResultsWe found statistical differences between pregnancy and birth outcomes during the COVID-19 pandemic compared to one year before. The risk of preeclampsia, gestational diabetes, cesarean section, preterm birth and NICU admission were clinically significant. Also, there was a significant decrease in mean gestational age.ConclusionThe COVID-19 pandemic has affected the pregnancy outcome by increasing morbidities and complications during pregnancy, birth, and postpartum. In addition, extensive quarantine outbreaks disrupted the healthcare system and hindered access to prenatal services. It is necessary to develop preventive and therapeutic care protocols for similar pandemic conditions.

What is Learned Determines How Pavlovian Conditioned Fear is Consolidated in the Brain.

Activity in the basolateral amygdala complex (BLA) is needed to encode fears acquired through contact with both innate sources of danger (i.e., things that are painful) and learned sources of danger (e.g., being threatened with a gun). However, within the BLA, the molecular processes required to consolidate the two types of fear are not the same: protein synthesis is needed to consolidate the first type of fear (so-called first-order fear) but not the latter (so-called second-order fear). The present study examined why first- and second-order fears differ in this respect. Specifically, it used a range of conditioning protocols in male and female rats, and assessed the effects of a BLA infusion of the protein synthesis inhibitor, cycloheximide, on first- and second-order conditioned fear. The results revealed that the differential protein synthesis requirements for consolidation of first- and second-order fears reflect differences in what is learned in each case. Protein synthesis in the BLA is needed to consolidate fears that result from encoding of relations between stimuli in the environment (stimulus-stimulus associations, typical for first-order fear) but is not needed to consolidate fears that form when environmental stimuli associate directly with fear responses emitted by the animal (stimulus-response associations, typical for second-order fear). Thus, the substrates of Pavlovian fear conditioning in the BLA depend on the way that the environment impinges upon the animal. This is discussed with respect to theories of amygdala function in Pavlovian fear conditioning, and ways in which stimulus-response associations might be consolidated in the brain.

ADVANCING THE UNDERSTANDING OF PM FILTER MASS STABILITY: UNVEILING THE INFLUENCE OF HUMIDITY AND TEMPERATURE

The intricate interplay between humidity and temperature on PM filter performance has remaineda subject of profound scientific interest. By employing fully-automated weighing method anda two-factor regression model, the study aimed to evaluate mass variations of unloaded PM filtersunder diverse humidity and temperature conditions. Existing guidelines, as posited by the USEPA and the European Standard (EN), have demonstrated a pronounced disparity. The US EPAadvocates a narrow humidity range of 30–40% RH, while the EN suggests a broader range of40–50% RH. The results of this investigation confirm the US EPA’s guidelines, which exhibitedsuperior filter mass stability under varying humidity. In controlled stable temperature conditionsof 20C, the research unveiled significant variations in filter mass as RH% increased from 50%to 55%. It has been proven that under stable temperature conditions (20C) inside a weighingrobot, an increase in relative air humidity from 50% to 55% results in filters mass addition by15 μg (Q, quartz fibre filters); by 93 μg (PTFE filters); by 9 μg (G, glass fibre filters); by 112 μg (PA,polyamide filters) and by 20 μg (PC, polycarbonate filters). Further exploration of the conditioningranges prescribed by the EN 12341:2014 standard, the study highlighted glass fibre filters as beingnotably stable, while polyamide membrane filters posed intriguing challenges potentially relatedto ionization insufficiencies during the equilibration stage. These findings bear significance forfilter manufacturing and conditioning protocols, potentially enhancing the precision of air qualitymonitoring practices.

GnRH antagonist protocol versus progestin-primed ovarian stimulation in patients with polycystic ovary syndrome: a systematic review and meta-analysis.

The aim of this meta-analysis was comparing the efficacy of GnRH antagonist (GnRH-ant) protocol and progestin-primed ovarian stimulation (PPOS) in polycystic ovarian syndrome (PCOS) women. A search was conducted from PubMed, Embase, The Cochrane library, Web of Science, and Scopus databases to collect clinical papers regarding GnRH-ant protocol and PPOS protocol from inception to September 2023. Subsequently, the retrieved documents were screened, and the content of the documents that conformed to the requirements was extracted. Moreover, statistical meta-analyses were conducted using the RevMan 5.4 software. Furthermore, with the use of a star-based system and the Cochrane handbook, the methodological quality of the covered papers was evaluated on the Ottawa-Newcastle scale. A total of eight papers were covered in the meta-analysis, with 2156 PCOS women enrolled (i.e., 1085 patients in the GnRH-ant protocol group and 1071 patients in the PPOS group). As indicated by the meta-analysis results, the PPOS group was correlated with a lower risk of ovarian hyperstimulation syndrome (OHSS) (SMD = 9.24, [95% CI: (2.50, 34.21)], P = 0.0009), more gonadotropin (Gn) dose (SMD = - 0.34, [95% CI: (- 0.56, - 0.13)], P = 0.002) compared with GnRH-ant group. No statistical difference was identified on the oocytes condition and pregnancy outcomes. As revealed by the data of this study, the progesterone protocol is comparable with the GnRH-ant protocol in oocytes condition and clinical outcomes. The progestin-primed ovarian stimulation could serve as an alternative for polycystic ovarian syndrome women who have failed in GnRH antagonist protocol. The above-described conclusions should be verified by more high-quality papers due to the limitation of the number and quality of included papers. PROSPERO registration: CRD42023411284.

Abstract 13851: CAR-T Cells: A Potential Novel Strategy for Mitigating Fibrosis in Duchenne Muscular Dystrophy

Introduction: Chimeric Antigen T (CAR)-T cells have proven effective preclinically for mitigating cardiac fibrosis in hypertensive cardiomyopathy. Hypothesis: We assessed whether this approach could be applied to Duchenne Muscular Dystrophy (DMD) by targeting Fibroblast Activating Protein (FAP)-expressing activated fibroblasts in cardiac and skeletal muscle fibrosis. Methods: A protocol for the lymphodepletion conditioning of mice was developed to optimize the dosing of cyclophosphamide. Next, immune-magnetically selected T cells were retrovirally transduced to target FAP (FAP-CAR) and quality-controlled by co-culture killing assays using FAP-expressing HEK target cells. Finally, lymphodepleted D2. mdx mice were intravenously injected with 10 7 FAP-CAR T cells (n=9) or 10 7 GFP-T cells (n=9) or Bovine Serum Albumin (BSA, n=8). Cardiac and skeletal muscle end points were assessed 2 and 5 weeks after treatment. Results: In vitro , the engineered CAR-T cells expressed activation markers (CD69, PD-1) and released large amounts of granzyme, perforin and interferon γ upon exposure to FAP-expressing target cells. One IP injection of cyclophosphamide (3mg) 4 days before treatment was safe and induced a lymphodepletion which enabled robust in vivo expansion of FAP-CAR T cell assessed by flow cytometry in lymphoid organs and blood: 10 5 , 2.10 6 and 10 7 detected CAR-T cells at day 3, 5 and 7 post-injections, respectively. This was paralleled by a more than a 2-fold decrease in endogenous FAP expression in skeletal muscles, as assessed by PCR at day 5 post-injections, and measurable FAP-CAR levels in the spleen compared with GFP-T cell controls. In vivo , FAP-CAR T cells significantly improved LV function with an EF change from baseline (Mean±SEM) of 33.1% ± 6.7% in FAP-CAR vs. 3.7% ± 6.4% and -9.6% ± 7.9% in GFP-T and BSA ( p &lt;0.037 and p &lt;0.005, respectively) at 2 weeks. The benefit was maintained at 5 weeks post-treatment. Several markers of fibrosis, particularly collagens 1 and 3, were also down-regulated in heart and muscles. Conclusions: FAP-CAR-T cells might represent a new therapeutic option for mitigating fibrosis in DMD, likely in conjunction with approaches aimed at addressing the root cause of the disease through a re-expression of a functional dystrophin.

Low Disease Relapse and High Survival in Non-Myeloablative Two-Step Haploidentical Transplant, Results of a Prospective Trial

Introduction We previously developed a two-step approach that separates the lymphoid and myeloid portions of the graft, allowing a consistent T cell dosing and sparing the stem cells from the effect of cyclophosphamide. The two-step approach demonstrated safety and efficacy in patients treated with a myeloablative conditioning protocol. Here, we extended our 2-step platform to older and less fit patients and explored the effects of using a high dose of T cells on disease relapse and transplant outcomes. Methods Patients received fludarabine 30mg/m 2 IV daily for 3 days, from day -10 to day -8. Two hundred cGy total body irradiation (TBI) was given on day -7. This was increased to 400 cGy TBI in 2 doses after 13 patients had been treated. A fixed dose of 2 x 10 8/kg CD3+ T cells was given on day -6, followed 2 days later by cyclophosphamide 60mg/kg IV daily on day -3 and day -2. Tacrolimus and mycophenolic acid were started on day -1, followed by infusion of CD34-selected stem cells on day 0. Results Thirty-three patients with hematologic malignancies were treated (Table 1). Majority were haploidentical transplants (91%), and the rest were matched related donors. Median age was 68 (range, 33-76) years, with 64% patients &amp;gt;65 years old. Median follow-up was 31 months (range, 0-76 months). Median HCT-comorbidity score was 4 (range, 0-9). Forty-seven percent had high or very high-risk disease risk index. Twenty-seven percent had prior autologous transplant. Overall survival was 75% at 1 year and 50% at 3 years. The cumulative incidence (CI) of non-relapse mortality (NRM) and relapse were 22% and 31% at 3 years. However, the CI of relapse was much lower for patients treated with 400 cGy TBI versus those treated with 200 cGy TBI (6% vs 54%, p = 0.017) (Figure 1), while NRM was similar (25% vs 15%, p = 0.348). This contributed to a very high survival of 69% in patients who received the higher dose of TBI at 3 years, with median OS not reached. The median time to neutrophil and platelet recovery was 11 and 17 days, respectively. The median donor CD3+ T cell chimerism at day +28 was 100% (range, 71% to 100%). The CI of grade II acute graft-versus-host-disease (GVHD) was 23% and 27% at 100 days and 6 months, respectively. The CI of chronic GVHD was 8% at 3 years. There were no grade III or IV acute GVHD, no severe chronic GVHD and no deaths attributable to acute or chronic GVHD. There were 13 deaths in the study, of which 7 died from disease relapse, 3 died from toxicity related to treatment regimen, and 2 died from infection. Conclusions The NMA two-step approach allo-SCT showed a low disease relapse rate and high survival in patients treated with 400 cGy TBI, despite a generally older and more medically compromised patient population.

PEEK surface treatment on surface roughness and bond integrity to composite resin utilizing Er: YAG, Rosebengal activated by PDT, and aluminum trioxide particles

AimsTo evaluate the impact of conditioning protocols, aluminum trioxide (Al2O3), Er:YAG laser (EYL), and Rosebengal (RB), on the surface roughness (Ra) and shear bond strength (SBS) of polyetheretherketone (PEEK) attached to composite restorations. MethodEighty PEEK discs in total were produced and then divided into four groups (n = 20). Group1:Sulfuric acid (SA), Group 2: PDT (RB), Group 3: Al2O3, Group 4 EYL, respectively. The Ra of PEEK discs was evaluated using the surface profilometer. After being luted, the discs were attached to composite resin discs. After that, samples were put to SBS testing on a Universal testing apparatus. A stereo microscope was also used to evaluate the type of breakdown. The data were analyzed using Tukey's test and one-way analysis of variance. ResultsThe SA treated group exhibited the highest Ra. Nevertheless, the RB specimens activated by PDT treatment had the lowest mean Ra score. The group that received the treatment of SA exhibited the highest average score of SBS. In contrast, specimens treated with PDT and activated by RB exhibited the lowest levels of bond fidelity. Cohesive failure emerges as the prevailing kind of fracture within the various groups subjected to testing. ConclusionThe utilization of Al2O3, RB activated by PDT, and EYL shows promise as a viable substitute for Sulfuric acid in enhancing the bond integrity of composite cement and surface roughness in PEEK materials

Identification of clinical factors impacting outcome in patients undergoing autologous hematopoietic cell transplantation after BEAM and TEAM conditioning.

Organ dysfunction, including pulmonary function impairment, plays a key role in the choice of conditioning chemotherapy before autologous hematopoietic stem cell transplantation (auto-HSCT). Replacement of BCNU/carmustine as part of BEAM (BCNU/carmustine, etoposide, cytarabine, and melphalan) conditioning protocol by thiotepa (TEAM) reduces pulmonary toxicity while maintaining efficacy. We retrospectively analyzed the association of clinical characteristics, comorbidities, and organ function with outcomes after conditioning with BEAM or TEAM. Three hundred ninety-six patients undergoing auto-HSCT (n = 333 with BEAM; n = 63 with TEAM) at our institution between 2008 and 2021 were included in this study. In the multivariate analysis, CO-diffusion capacity corrected for hemoglobin (DLCOcSB) ≤ 60% of predicted, progressive disease (PD) before auto-HSCT, Karnofsky performance score (KPS) ≤ 80%, HCT-CI score ≥ 4, and cardiac disease before auto-HSCT were associated with decreased overall survival (OS) in patients treated with BEAM. In contrast, only PD before auto-HSCT was identified in patients treated with TEAM. Patients conditioned with BEAM and DLCOcSB ≤ 60% had higher non-relapse mortality, including pulmonary cause of death. In summary, we have identified clinical and pulmonary risk factors associated with worse outcomes in patients conditioned with BEAM compared to TEAM. Our data suggest TEAM conditioning as a valid alternative for patients with comorbidities, including pulmonary dysfunction and/or poorer performance scores, before auto-HSCT.

Multi-valued model checking IoT and intelligent systems with commitment protocols in multi-source data environments

In today’s world of connectivity, various domains use different multi-sensor Internet of Things (IoT) and Intelligent Systems (IS) applications. These applications involve extensive interactions between thousands or millions of components in open environments, which challenges verifying their reliability and efficiency. This paper introduces the first investigation in verifying IoT applications and intelligent systems in multi-source data settings with multi-agent commitment protocols in uncertain or inconsistent environments. Specifically, we present original and efficient solutions for modeling and verifying these systems with conditional and unconditional commitment protocols under uncertain or inconsistent settings. We introduce 4v-CTLc and 4v-CTLcc, multi-valued logics of commitment for reasoning about inconsistency over these systems that expand 3v-CTLc and 3v-CTLcc for reasoning about uncertainty. Moreover, we introduce new reduction algorithms for reducing our multi-valued model checking problems to the two-valued ones. To implement these algorithms, we develop two new automatic verification tools. The first tool translates the multi-valued logics to CTL and automatically interacts with the NuSMV model checker. The second tool translates these logics to the two-valued versions, CTLc and CTLcc, and automatically interacts with the MCMAS+ model checker. We apply our verification approaches to a Smart Home, a Smart Hospital and a Smart Mortgage system with multi-source data as case studies using sets of properties, including safety, liveness and reachability. The experimental results obtained by the proposed multi-valued model checking techniques proved these techniques’ high efficiency and applicability to modeling and verifying intelligent and autonomous multi-source data systems.

Prognostic significance of extramedullary disease (EMD) detected on pre-transplant 18F-FDG PET/CT in patients with multiple myeloma: Results of PIPET-M trial

BackgroundIt is difficult to prognosticate the post-Autologous Stem Cell Transplant (ASCT) responses in multiple myeloma (MM) with the currently available prognostication models. 18F-FDGPET/CT has numerous advantages to prognosticate the post-transplant responses by assessing extramedullary disease (EMD) in addition to the extent of active disease. We aimed at identifying the prognostic value of EMD in predicting progression-free survival (PFS) and overall survival (OS). MethodsThis is a single centre prospective study from western India during a study period of 2014–2022 (with a median follow-up of patients of 6 years). All ASCT patients underwent 18F-FDG-PET/CT as part of pre-transplant workup. The conditioning and treatment protocols were not modified based on PET/CT findings. EMD on PET/CT was correlated with pre-transplant biochemical markers and post-ASCT survival/ progression (as defined by revised IMWG criteria). Statistical analysis was done using SPSS ver. 20. ResultsPatients with pre-ASCT EMD had a hazard-ratio for post-transplant all-cause mortality of 5.46 (p-0.045). Pre-transplant β2M and LDH were significantly higher in patients with EMD (p-0.036). The 6-year median OS in patients with and without EMD were 57.1%, and 80.6% respectively. Kaplan-Meier analysis showed poorer OS in patients with EMD χ2 (1–0.496, p-0.481). There was no significant difference in clinical or biochemical EFS among patients with EMD. ConclusionEMD detected on 18F-FDG-PET/CT has a higher hazard for mortality and is significantly correlated with pre-transplant higher β2M and LDH levels. Thus, EMD by pre-transplant 18F-FDG-PET/CT has a significant prognostic role.

Spatiotemporal Variability in N-Nitrosodimethylamine Precursor Levels in a Watershed Impacted by Agricultural Activities and Municipal Wastewater Discharges and Effects of Lime Softening.

The Crow River, a tributary of the Mississippi River in Minnesota, U.S.A., that is impacted by agricultural activities and municipal wastewater discharges, was sampled approximately monthly at 12 locations over 18 months to investigate temporal and spatial variations in N-nitrosodimethylamine (NDMA) precursor levels. NDMA precursors were quantified primarily by measuring NDMA formed under the low chloramine dose uniform formation conditions protocol (NDMAUFC) and occasionally using the high dose formation potential protocol (NDMAFP). Raw water NDMAUFC concentrations (2.2 to 128 ng/L) exhibited substantial temporal variation but relatively little spatial variation. An increase in NDMAUFC was observed for 126 of 169 water samples after lime-softening treatment. A kinetic model indicates that under chloramine-limited UFC test conditions, the increase in NDMAUFC can be attributed to a decrease in competition between precursors and natural organic matter (NOM) for chloramines and reduced interactions of precursors with NOM. NDMAUFC concentrations correlated positively with dissolved nitrogen concentration (ρ = 0.44, p < 0.01) when excluding the spring snowmelt period and negatively correlated with dissolved organic carbon concentration (ρ = -0.47, p < 0.01). Overall, NDMA precursor levels were highly dynamic and strongly affected by lime-softening treatment.