Covert actions of epidural stimulation on spinal locomotor circuits.

Spinal circuitry produces the rhythm and patterning of locomotion. However, both descending and sensory inputs are required to initiate and adapt locomotion to the environment. Spinal cord injury (SCI) disrupts descending controls of the spinal cord, producing paralysis. Epidural stimulation (ES) is a promising clinical therapy for motor control recovery and is capable of reactivating the lumbar spinal locomotor networks, yet little is known about the effects of ES on locomotor neurons. Previously, we found that both sensory afferent pathways and serotonin exert mixed excitatory and inhibitory actions on lumbar interneurons involved in the generation of the locomotor rhythm, identified by the transcription factor Shox2. However, after chronic complete SCI, sensory afferent inputs to Shox2 interneurons become almost exclusively excitatory and Shox2 interneurons are supersensitive to serotonin. Here, we investigated the effects of ES on these SCI-induced changes. Inhibitory input from sensory pathways to Shox2 interneurons was maintained and serotonin supersensitivity was not observed in SCI mice that received daily sub-motor threshold ES. Interestingly, the effects of ES were maintained for at least three weeks after the ES was discontinued. In contrast, the effects of ES were not observed in Shox2 interneurons from mice that received ES after the establishment of the SCI-induced changes. Our results demonstrate mechanistic actions of ES at the level of identified spinal locomotor circuit neurons and the effectiveness of early treatment with ES on preservation of spinal locomotor circuitry after SCI, suggesting possible therapeutic benefits prior to the onset of motor rehabilitation.

Association of Language Preference with Therapeutic Care for Hospitalized COVID-19 Patients.

INTRODUCTION: There is a paucity of research investigating disparities in utilization of inpatient therapeutics for COVID-19 by language preference. The primary aim of this study was to assess if the likelihood of treatment with novel COVID-19 therapies differed for patients using a language other than English (LOE) relative to English-speaking patients. METHODS: This was a retrospective observational cohort study of COVID-19 patients hospitalized between March 1, 2020, and June 30, 2022, across 11 hospitals within a single not-for-profit health system. Multivariable relative risks were estimated for the impact of preferred language on the receipt of novel COVID-19 therapies: baricitinib, remdesivir, tocilizumab, and convalescent plasma. RESULTS: This study included 12,510 hospitalized adults with English as the most common preferred language (92.3%) followed by Spanish (3.1%), Somali (1.3%), Russian (0.9%), and Hmong (0.6%). Spanish speakers were more likely to receive any of the novel COVID-19 therapies compared to English speakers (RR 1.45; CI 1.32-1.59). Estimates for Hmong, Somali, Russian, and Other language groups were not statistically significant and closer to the null (aRR range, 0.89-1.12). CONCLUSION: Linguistic patterns in health outcomes expose inherent heterogeneity within racial and ethnic groups. Our study found that Spanish speakers were nearly 1.5 times more likely to receive any of the four novel inpatient COVID-19 therapeutics in comparison to English speakers. Future research is needed to explore the reasons for the heterogeneous findings including temporal influence, cultural factors, informed consent comprehension, and therapeutic hesitancy in all groups.

Microwave Scissors-Based Sutureless Laparoscopic Partial Nephrectomy Versus Conventional Open Partial Nephrectomy in a Porcine Model: Usefulness and Complications.

BACKGROUND: This study aimed to compare the benefits and safety of microwave scissors-based sutureless laparoscopic partial nephrectomy (MSLPN) with those of conventional open partial nephrectomy (cOPN). METHODS: Each kidney in nine pigs underwent MSLPN using microwave scissors (MWS) via transperitoneal laparoscopy or cOPN via retroperitoneal open laparotomy. The kidney's lower and upper poles were resected under temporary hilar-clamping. The renal calyces exposed during renal resections were sealed and transected using MWS in MSLPN and were sutured in cOPN. For MWS, the generator's power output was 60 W. Data on procedure time (PT), ischemic time (IT), blood loss (BL), normal nephron loss (NNL), and extravasation during retrograde pyelogram were compared between the two techniques. RESULTS: The authors successfully performed 22 MSLPNs and 10 cOPNs. Compared with cOPN, MSLPN was associated with significantly lower PT (median, 9.2 vs 13.0 min; p = 0.026), IT (median, 5.9 vs 9.0 min; p < 0.001), BL (median, 14.4 vs 38.3 mL; p = 0.043), and NNL (median, 7.6 vs 9.4 mm; p = 0.004). However, the extravasation rate was higher in the MSLPN group than in the cOPN group (54.5 % [n = 12] vs 30.0 % [n = 3]), albeit without a significant difference (p = 0.265). Pelvic stenosis occurred in one MSLPN procedure that involved deep lower pole resection near the kidney hilum. CONCLUSIONS: The study data show that MSLPN can improve intraoperative outcomes while reducing technical demands for selected patients with non-hilar-localized renal tumors. However, renal calyces, if violated, should be additionally sutured to prevent urine leakage.

Varying the position of phospholipid acyl chain unsaturation modulates hopanoid and sterol ordering.

The cell membrane must balance mechanical stability with fluidity to function as both a barrier and an organizational platform. Key to this balance is the ordering of hydrocarbon chains and the packing of lipids. Many eukaryotes synthesize sterols, which are uniquely capable of modulating the lipid order to decouple membrane stability from fluidity. Ancient sterol analogs known as hopanoids are found in many bacteria and proposed as ancestral ordering lipids. The juxtaposition of sterols and hopanoids in extant organisms prompts us to ask why both pathways persist, especially in light of their convergent ability to order lipids. In this work, simulations, monolayer experiments, and cellular assays show that hopanoids and sterols order unsaturated phospholipids differently based on the position of double bonds in the phospholipid acyl chain. We find that cholesterol and diplopterol's methyl group distributions lead to distinct effects on unsaturated lipids. In Mesoplasma florum, diplopterol's constrained ordering capacity reduces membrane resistance to osmotic stress, unlike cholesterol. These findings suggest that cholesterol's broader lipid-ordering ability may have facilitated the exploration of a more diverse lipidomic landscape in eukaryotic membranes.

Resf1 is a compound G4 quadruplex-associated tumor suppressor for triple negative breast cancer.

Patients with ER-negative breast cancer have the worst prognosis of all breast cancer subtypes, often experiencing rapid recurrence or progression to metastatic disease shortly after diagnosis. Given that metastasis is the primary cause of mortality in most solid tumors, understanding metastatic biology is crucial for effective intervention. Using a mouse systems genetics approach, we previously identified 12 genes associated with metastatic susceptibility. Here, we extend those studies to identify Resf1, a poorly characterized gene, as a novel metastasis susceptibility gene in ER- breast cancer. Resf1 is a large, unstructured protein with an evolutionarily conserved intron-exon structure, but with poor amino acid conservation. CRISPR or gene trap mouse models crossed to the Polyoma Middle-T antigen genetically engineered mouse model (MMTV-PyMT) demonstrated that reduction of Resf1 resulted in a significant increase in tumor growth, a shortened overall survival time, and increased incidence and number of lung metastases, consistent with patient data. Furthermore, an analysis of matched tail and primary tissues revealed loss of the wildtype copy in tumor tissue, consistent with Resf1 being a tumor suppressor. Mechanistic analysis revealed a potential role of Resf1 in transcriptional control through association with compound G4 quadruplexes in expressed sequences, particularly those associated with ribosomal biogenesis. These results suggest that loss of Resf1 enhances tumor progression in ER- breast cancer through multiple alterations in both transcriptional and translational control.

Photodynamic treatment increases the lifespan and oxidative stress resistance of Caenorhabditis elegans.

Photodynamic therapy is a noninvasive treatment in which specific photosensitizers and light are used to produce high amounts of reactive oxygen species (ROS), which can be employed for targeted tissue destruction in cancer treatment or antimicrobial therapy. However, it remains unknown whether lower amounts of ROS produced by mild photodynamic therapy increase lifespan and stress resistance at the organism level. Here, we introduce a novel photodynamic treatment (PDTr) that uses 20 µM hypericin, a photosensitizer that originates from Hypericum perforatum, and orange light (590 nm, 5.4 W/m2, 1 min) to induce intracellular ROS formation (ROS), thereby resulting in lifespan extension and improved stress resistance in C. elegans. The PDTr-induced increase in longevity was abrogated by N-acetyl cysteine, suggesting the hormetic response was driven by prooxidative mechanisms. PDTr activated the translocation of SKN-1/NRF-2 and DAF-16/FOXO, leading to elevated expression of downstream oxidative stress-responsive genes, including ctl-1, gst-4, and sod-3. In summary, our findings suggest a novel PDTr method that extends the lifespan of C. elegans under both normal and oxidative stress conditions through the activation of SKN-1 and DAF-16 via the involvement of many antioxidant genes.

A practical approach to nutritional intervention for people with chronic kidney disease in Vietnam.

BACKGROUND AND OBJECTIVES: A comprehensive nutritional management is necessary for favourable outcomes in patients with chronic kidney disease (CKD). We aimed to assess the changes in nutritional status and disease progression with nutritional management where renal replacement therapy (RRT) was not in place. METHODS AND STUDY DESIGN: A quasi-experiment intervention was conducted on 70 CKD patients at stages 3-5 from July to December 2022. Participants were excluded if they underwent RRT, including dialy-sis (hemodialysis or peritoneal dialysis), or kidney transplantation. The nutritional regimen covered nutrition-al counseling, samples of the dietary menu, and supplement products. We evaluated nutritional status using Subjective Global Assessment (SGA) scale and sub-clinical blood test at T0 (hospital admission) and T1 (two weeks after the admission or 24 hours before the discharge). RESULTS: After the intervention, the number of patients classified as malnutrition or at risk of malnourished reduced significantly (65.7% to 54.3% and 25.7% and 5.7%, respectively). The serum concentration of urea, creatinine and parathyroid hormone decreased remarkably, especially in patients receiving nutritional management. In the intervention group, the dietary pattern provided increased intakes of calcium and iron at T1, while phosphorus, sodium and potassium decreased after follow-up. Nausea/vomiting, loss of appetite, tiredness and sleep disorders were improved in the intervention compared to the control group. CONCLUSIONS: Nutritional therapy enhanced the nutritional sta-tus, and quality of dietary and renal function in CKD patients without RRT. Applying nutrition education and treatment at an early stage can slow CKD progression, which should be applicable elsewhere in Vietnam.

Impact of Modifications from Potassium Hydroxide on Porous Semi-IPN Hydrogel Properties and Its Application in Cultivation.

This study synthesized and modified a semi-interpenetrating polymer network hydrogel from polyacrylamide, N,N'-dimethylacrylamide, and maleic acid in a potassium hydroxide solution. The chemical composition, interior morphology, thermal properties, mechanical characteristics, and swelling behaviors of the initial hydrogel (SH) and modified hydrogel (SB) in water, salt solutions, and buffer solutions were investigated. Hydrogels were used as phosphate fertilizer (PF) carriers and applied in farming techniques by evaluating their impact on soil properties and the growth of mustard greens. Fourier-transform infrared spectra confirmed the chemical composition of SH, SB, and PF-adsorbed hydrogels. Scanning electron microscopy images revealed that modification increased the largest pore size from 817 to 1513 µm for SH and SB hydrogels, respectively. After modification, the hydrogels had positive changes in the swelling ratio, swelling kinetics, thermal properties, mechanical and rheological properties, PF absorption, and PF release. The modification also increased the maximum amount of PF loaded into the hydrogel from 710.8 mg/g to 770.9 mg/g, while the maximum % release of PF slightly increased from 84.42% to 85.80%. In addition, to evaluate the PF release mechanism and the factors that influence this process, four kinetic models were applied to confirm the best-fit model, which included zero-order, first-order, Higuchi, and Korsmeyer-Peppas. In addition, after six cycles of absorption and release in the soil, the hydrogels retained their original shapes, causing no alkalinization or acidification. At the same time, the moisture content was higher as SB was used. Finally, modifying the hydrogel increased the mustard greens' lifespan from 20 to 32 days. These results showed the potential applications of modified semi-IPN hydrogel materials in cultivation.

Improving nitrogen content in soil and lemon balm (Melissa officinalis L.) yield by purple nonsulfur bacteria Rhodopseudomonas palustris in two consecutive seasons.

The study was conducted to assess the effects of nitrogen (N)-fixing purple nonsulfur bacteria (PNSB) Rhodopseudomonas palustris TLS06, VNW02, VNW64, and VNS89 on soil fertility, N uptake, essential oil (EO) content, growth, and yield of lemon balm. The experiment followed a completely randomized block design with 9 treatments and 3 replications. The treatments consisted of (i) applying 100% N as the recommended fertilizer rate (RFR), (ii) applying 85% N as RFR, (iii) applying 70% N as RFR, (iv) applying 55% N as RFR, (v) the treatment ii combined with N-PNSB, (vi) the treatment iii combined with N-PNSB, (vii) the treatment iv combined with N-PNSB, (viii) 0% as RFR combined with N-PNSB, and (ix) 0% N as RFR. The results showed that applying N-PNSB increased the plant height, and the number of primary branches in both seasons. In addition, the treatment without N fertilizer combined with N-PNSB increased stem leaf biomass by 41.2 and 50.3% in both seasons as compared with the treatment without neither N fertilizer nor N-PNSB. For soil properties, among treatments without N fertilizer, the treatment with N-PNSB increased concentrations of NH4+, soluble P, and exchangeable K+ by 41.3, 41.4, and 26.8%, respectively, as compared with the treatment without N-PNSB at the end of the second season. Applying 85% N as RFR combined with N-PNSB had a greater yield by 5.78-11.8% as compared with the treatment with 100% N as RFR, and a greater EO content by 23% as compared with the treatment with 85% N as RFR.

SMARCD1 is a "Goldilocks" metastasis modifier.

Breast cancer is the most frequently diagnosed cancer worldwide, constituting around 15% of all diagnosed cancers in 2023. The predominant cause of breast cancer-related mortality is metastasis to distant essential organs, and a lack of metastasis-targeted therapies perpetuates dismal outcomes for late-stage patients. However, through our use of meiotic genetics to study inherited transcriptional network regulation, we have identified a new class of "Goldilocks" genes that are promising candidates for the development of metastasis-targeted therapeutics. Building upon previous work that implicated the CCR4-NOT RNA deadenylase complex in metastasis, we now demonstrate that the RNA-binding proteins (RNA-BPs) NANOS1, PUM2, and CPSF4 also regulate metastatic potential. Using cell lines, 3D culture, mouse models, and clinical data, we pinpoint Smarcd1 mRNA as a key target of all three RNA-BPs. Strikingly, both high and low expression of Smarcd1 is associated with positive clinical outcomes, while intermediate expression significantly reduces the probability of survival. Applying the theory of "essential genes" from evolution, we identify an additional 50 genes that span several cellular processes and must be maintained within a discrete window of expression for metastasis to occur. In the case of Smarcd1, small perturbations in its expression level significantly reduce metastasis in laboratory mouse models and alter splicing programs relevant to the ER+/HER2-enriched breast cancer subtype. The identification of subtype-specific "Goldilocks" metastasis modifier genes introduces a new class of genes and potential catalogue of novel targets that, when therapeutically "nudged" in either direction, may significantly improve late-stage patient outcomes.

Varying the position of phospholipid acyl chain unsaturation modulates hopanoid and sterol ordering.

The cell membrane must balance mechanical stability with fluidity to function as both a barrier and an organizational platform. Key to this balance is the thermodynamic ordering of lipids. Most Eukaryotes employ sterols, which are uniquely capable of modulating lipid order to decouple membrane stability from fluidity. Ancient sterol analogues known as hopanoids are found in many bacteria and are proposed as ancestral ordering lipids. The juxtaposition of sterols and hopanoids in extant organisms prompts us to ask why both pathways persist, especially in light of their convergent ability to order lipids. We reveal that both hopanoids and sterols order unsaturated phospholipids differently based on the position of double bonds in the phospholipid's acyl chain. We find that cholesterol and diplopterol's methyl group distributions lead to distinct effects on unsaturated lipids. In Mesoplasma florum, diplopterol's constrained ordering capacity reduces membrane resistance to osmotic stress, unlike cholesterol. These findings suggest cholesterol's broader lipid ordering ability may have facilitated the exploration of a more diverse lipidomic landscape in eukaryotic membranes.

Loss of NAT10 disrupts enhancer organization via p300 mislocalization and suppresses transcription of genes necessary for metastasis progression.

Acetylation of protein and RNA represent a critical event for development and cancer progression. NAT10 is the only known RNA acetylase that catalyzes the N4-actylcytidine (ac4C) modification of RNAs. Here, we show that the loss of NAT10 significantly decreases lung metastasis in allograft and genetically engineered mouse models of breast cancer. NAT10 interacts with a mechanosensitive, metastasis susceptibility protein complex at the nuclear pore. In addition to its canonical role in RNA acetylation, we find that NAT10 interacts with p300 at gene enhancers. NAT10 loss is associated with p300 mislocalization into heterochromatin regions. NAT10 depletion disrupts enhancer organization, leading to alteration of gene transcription necessary for metastatic progression, including reduced myeloid cell-recruiting chemokines that results in a less metastasis-prone tumor microenvironment. Our study uncovers a distinct role of NAT10 in enhancer organization of metastatic tumor cells and suggests its involvement in the tumor-immune crosstalk dictating metastatic outcomes.

Intussusception and Other Adverse Event Surveillance after Pilot Introduction of Rotavirus Vaccine in Nam Dinh and Thua Thien Hue Provinces-Vietnam, 2017-2021.

Rotavin-M1 (POLYVAC) was licensed in Vietnam in 2012. The association of Rotavin-M1 with intussusception, a rare adverse event associated with rotavirus vaccines, and with adverse events following immunization (AEFI) have not been evaluated and monitored under conditions of routine use. From February 2017 to May 2021, we conducted a pilot introduction of Rotavin-M1 into the routine vaccination program in two provinces. Surveillance for intussusception was conducted at six sentinel hospitals. AEFI reports at 30 min and 7 days after vaccination were recorded. Among 443 children <12 months of age admitted for intussusception, most (92.3%) were children ≥ 6 months. Of the 388 children who were age-eligible to receive Rotavin-M1, 116 (29.9%) had received ≥1 dose. No intussusception cases occurred in the 1-21 days after dose 1 and one case occurred on day 21 after dose 2. Among the 45,367 children who received ≥1 dose of Rotavin-M1, 9.5% of children reported at least one AEFI after dose 1 and 7.3% after dose 2. Significantly higher AEFI rates occurred among children given Rotavin-M1 with pentavalent vaccines (Quinvaxem®, ComBE Five®) compared to Rotavin-M1 without pentavalent vaccines. There was no association between intussusception and Rotavin-M1. The vaccine was generally safe when administered alone and when co-administered with other vaccines.

Comparison of off-clamp microwave scissors-based sutureless partial nephrectomy versus on-clamp conventional partial nephrectomy in a canine model.

Objectives: To compare the usefulness and safety of off-clamp microwave scissors-based sutureless partial nephrectomy (MSPN) with on-clamp conventional partial nephrectomy (cPN) in dogs. Methods: We performed off-clamp MSPN using microwave scissors (MWS) in six dogs, and on-clamp cPN in three dogs, in two-stage experiments. The bilateral kidney upper poles were resected via a midline incision under general anesthesia. After 14 days of follow-up, the lower pole resections were performed. The renal calyces exposed during renal resections were sealed and transected using MWS in off-clamp MSPN and were sutured in on-clamp cPN. In the off-clamp MSPN group, the generator's power output of MWS was set as either 50 W or 60 W for each kidney side. We compared the procedure time (PT), ischemic time (IT), blood loss (BL), and normal nephron loss (NNL) between the two techniques using the Mann-Whitney U-test. Results: We successfully performed 24 off-clamp MSPNs and 12 on-clamp cPNs. The off-clamp MSPN was significantly superior to on-clamp cPN in avoiding renal ischemia (median IT, 0 min vs. 8.6 min, p < 0.001) and reducing PT (median PT, 5.8 min vs. 11.5 min, p < 0.001) and NNL (median NNL, 5.3 mm vs. 6.0 mm, p = 0.006) with comparable BL (median BL, 20.9 ml vs. 23.2 ml, p = 0.804). No bleeding and major urine leakage were noted during the reoperations. Conclusions: Off-clamp MSPN outperforms on-clamp cPN in lowering the risks of postoperative renal function impairment in dogs.

Developing low-cost nanohybrids of ZnO nanorods and multi-shaped silver nanoparticles for broadband photodetectors.

Photodetectors are essential elements for various applications like fiber optic communication systems, biomedical imaging, and so on. Thus, improving the performance and reducing the material costs of photodetectors would act as a motivation toward the future advancement of those applications. This study introduces the development of a nanohybrid of zinc oxide nanorods (ZnONRs) and multi-shaped silver nanoparticles MAgNPs through a simple solution process; in which ZnONRs are hybridized with MAgNPs to enable visible absorption through the surface plasmon resonance (SPR) effect. The photodetector based on ZnONRs/MAgNPs is responsive to visible light with representative wavelengths of 395, 464, 532 and 640 nm, and it exhibits high responsivity (R), photoconductive gain (G) and detectivity (D). The maximum R is calculated from the fitting curve of the responsivity-power relation with the value of 5.35 × 103 (mA W-1) at 395 nm excitation. The highest G and D reach 8.984 and 3.71 × 1010 Jones at that wavelength. This reveals the promise of our innovative broadband photodetector for practical usage.

Outcomes in patients discharged with extended venous thromboembolism prophylaxis after hospitalization with COVID-19.

BACKGROUND: Venous thromboembolism (VTE) is a known complication of coronavirus disease (COVID-19) in patients requiring hospitalization and intensive care. We examined the association between extended pharmacological VTE prophylaxis and outcomes among patients hospitalized with COVID-19. METHODS: This was a retrospective cohort study of patients with an index positive SARS-CoV-2 polymerase chain reaction (PCR) test at the time of, or during hospitalization. Patients who were prescribed extended pharmacological VTE prophylaxis were compared against patients who were not. Multivariable logistic regression was used to produce odds ratio (OR) estimates and Cox proportional hazard models for hazard ratios (HR) with 95% CI to examine the association between pharmacological VTE prophylaxis and outcomes of interest. Primary outcomes were 30- and 90-day VTE events. Secondary outcomes included 30- and 90-day mortality, 30-day superficial venous thrombosis (SVT), acute myocardial infarction (MI), acute ischemic stroke, critical limb ischemia, clinically significant bleeding, and inpatient readmissions. RESULTS: A total of 1936 patients were included in the study. Among them, 731 (38%) were discharged on extended pharmacological VTE prophylaxis. No significant difference was found in 30- and 90-day VTE events among groups. Patients discharged on extended VTE prophylaxis showed improved survival at 30 (HR: 0.35; 95% CI: 0.21-0.59) and 90 days (HR: 0.36; 95% CI: 0.23-0.55) and reduced inpatient readmission at 30 days (OR: 0.12; 95% CI: 0.04-0.33) when compared to those without. CONCLUSION: Patients discharged on extended VTE prophylaxis after hospitalization due to COVID-19 had similar thrombotic events on follow-up. However, use of extended VTE prophylaxis was associated with improved 30- and 90-day survival and reduced risk of 30-day inpatient readmission.

Prophylactic epinephrine attenuates severe bleeding in lung transplantation patients undergoing transbronchial lung biopsy: Results of the PROPHET randomized trial.

BACKGROUND: Severe hemorrhage is an uncommon yet potentially life-threatening complication of transbronchial lung biopsy. Lung transplantation recipients undergo multiple bronchoscopies with biopsy and are considered to be at an increased risk for bleeding from transbronchial biopsy, independent of traditional risk factors. We aimed to evaluate the efficacy and safety of endobronchial administration of prophylactic topical epinephrine in attenuating transbronchial biopsy-related hemorrhage in lung transplant recipients. METHODS: The Prophylactic Epinephrine for the Prevention of Transbronchial Lung Biopsy-related Bleeding in Lung Transplant Recipients study was a 2-center, randomized, double blind, placebo-controlled clinical trial. Participants undergoing transbronchial lung biopsy were randomized to receive 1:10,000-diluted topical epinephrine vs saline placebo administered prophylactically into the target segmental airway. Bleeding was graded based on a clinical severity scale. The primary efficacy outcome was incidence of severe or very severe hemorrhage. The primary safety outcome was a composite of 3-hours all-cause mortality and an acute cardiovascular event. RESULTS: A total of 66 lung transplantation recipients underwent 100 bronchoscopies during the study period. The primary outcome of severe or very severe hemorrhage occurred in 4 cases (8%) in the prophylactic epinephrine group and in 13 cases (24%) in the control group (p = 0.04). The composite primary safety outcome did not occur in any of the study groups. CONCLUSIONS: In lung transplantation recipients undergoing transbronchial lung biopsy, prophylactic administration of 1:10,000-diluted topical epinephrine into the target segmental airway before biopsy attenuates the incidence of significant endobronchial hemorrhage without conveying a significant cardiovascular risk. (ClinicalTrials.gov identifier: NCT03126968).

Self-organized yolk sac-like organoids allow for scalable generation of multipotent hematopoietic progenitor cells from induced pluripotent stem cells.

Although the differentiation of human induced pluripotent stem cells (hiPSCs) into various types of blood cells has been well established, approaches for clinical-scale production of multipotent hematopoietic progenitor cells (HPCs) remain challenging. We found that hiPSCs cocultured with stromal cells as spheroids (hematopoietic spheroids [Hp-spheroids]) can grow in a stirred bioreactor and develop into yolk sac-like organoids without the addition of exogenous factors. Hp-spheroid-induced organoids recapitulated a yolk sac-characteristic cellular complement and structures as well as the functional ability to generate HPCs with lympho-myeloid potential. Moreover, sequential hemato-vascular ontogenesis could also be observed during organoid formation. We demonstrated that organoid-induced HPCs can be differentiated into erythroid cells, macrophages, and T lymphocytes with current maturation protocols. Notably, the Hp-spheroid system can be performed in an autologous and xeno-free manner, thereby improving the feasibility of bulk production of hiPSC-derived HPCs in clinical, therapeutic contexts.

Evidence of internal structure of the transactional eHealth literacy among Vietnamese youth: An instrument validation study.

Background: The progression into the Digital Age has brought an array of novel skill requirements. Unlike traditional literacy, there are currently few measures that can reliably measure eHealth literacy. The Transactional Model of eHealth Literacy and subsequent Transactional eHealth Literacy Instrument may provide a feasible option for measuring eHealth literacy. Objective: This instrument has yet to be validated, which is the aim of this study. In particular, this article was conducted to validate the TeHLI to see which components of the tool (how many and which components included) would be the best fit statistically and whether the tool applies to groups of different characteristics. Methods: We conducted an online cross-sectional study among 236 Vietnamese young people. A exploratory factor analysis was used to identify the best fit model of the Transactional eHealth Literacy Instrument. A confirmatory factor analysis tested measurement invariance at four levels: configural, metric, scalar, and strict invariance. Only metric invariance was partially invariant, while the rest tested fully invariant. Even with partial metric invariance, there is reason to assume that functional, communicative, critical, and translational eHealth literacy (the four levels according to the transactional model) are consistently measured when deploying the Transactional eHealth Literacy Instrument across groups. Results: The study findings substantiate that the most optimal composition of the TeHLI consists of four factors: functional, communicative, critical, and translational eHealth literacy, with RMSEA = 0.116; CFI = 0.907, and the highest internal consistency (Cronbach's α = 0.91, 0.92, 0.88, and 0.92 for each factor respectively). After using measurement invariance, that gender, education, marital status, age, location, and household economy do not influence the way participants to respond to the TeHLI to the point that would introduce measurement bias. In other word, using TeHLI across population groups should not produce error margins that substantially differ from each other. Conclusions: This study suggests the instrument can be used for comparisons across groups and has the potential to generate high-quality data usable for informing change agents as to whether a particular population is proficient enough to adopt novel eHealth innovations.