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Salinity impacts crop growth and productivity and lowers the activities of rhizosphere microbiota. The identification and utilization of habitat-specific salinity-adapted plant growth-promoting rhizobacteria (PGPR) are considered alternative strategies to improve the growth and yields of crops in salinity-affected coastal agricultural fields. In this study, we characterize strain L1I39T, the first Aquabacter species with PGPR traits isolated from a salt-tolerant pokkali rice cultivated in brackish environments. L1I39T is positive for 1-aminocyclopropane-1-carboxylate deaminase activity and nitrogen fixation and can promote pokkali rice growth by supplying fixed nitrogen under a nitrogen-deficient seawater condition. Importantly, enhanced plant growth and efficient root colonization were evident in L1I39T-inoculated plants grown under 20% seawater but not in zero-seawater conditions, identifying brackish conditions as a key local environmental factor critical for L1I39T-pokkali rice symbiosis. Detailed physiological studies revealed that L1I39T is well-adapted to brackish environments. In-depth genome analysis of L1I39T identified multiple gene systems contributing to its plant-associated lifestyle and brackish adaptations. The 16S rRNA-based metagenomic study identified L1I39T as an important rare PGPR taxon. Based on the polyphasic taxonomy analysis, we established strain L1I39T as a novel Aquabacter species and proposed Aquabacter pokkalii sp nov. Overall, this study provides a better understanding of a marine-adapted PGPR strain L1I39T that may perform a substantial role in host growth and health in nitrogen-poor brackish environments.
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Fijación del Nitrógeno , Oryza , Filogenia , Raíces de Plantas , Oryza/microbiología , Oryza/genética , Oryza/crecimiento & desarrollo , Raíces de Plantas/microbiología , Raíces de Plantas/crecimiento & desarrollo , Rizosfera , Salinidad , Adaptación Fisiológica/genética , Simbiosis , ARN Ribosómico 16S/genéticaRESUMEN
Silver has long been recognized for its potent antimicrobial properties, but achieving a slow and longer-term delivery of silver ions presents significant challenges. Previous efforts to control silver ion dosages have struggled to sustain release for extended periods in biomimetic environments, especially in the presence of complex proteins. This challenge is underscored by the absence of technology for sustaining antimicrobial activity, especially in the context of orthopedic implants where long-term efficacy, extending beyond 7 days, is essential. In this study, the tunable, slow, and longer-term release of silver ions from the two-dimensional (2D) nanocapillaries of graphene oxide (GO) laminates incorporated with silver ions (Ag-GO) for antimicrobial applications are successfully demonstrated. To closely mimic a physiologically relevant serum-based environment, a novel in vitro study model using 100% fetal bovine serum (FBS) is introduced as the test medium for microbiology, biocompatibility, and bioactivity studies. To emulate fluid circulation in a physiological environment, the in vitro studies are challenged with serum exchange protocols on different days. The findings show that the Ag-GO coating can sustainably release silver ions at a minimum dosage of 10 µg cm-2 day-1, providing an effective and sustained antimicrobial barrier for over ten days.
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Textile effluent carries a range of dyes that may be recalcitrant and resistant to biodegradation. A unique consortium of the Fimbristylis dichotoma and Saccharomyces cerevisiae is exploited for the biodegradation of an azo dye Rubine GFL and actual textile effluent. This consortium enhances the rate of biodegradation of Rubine GFL and actual textile effluent with an excellent rate of biodegradation of 92% for Rubine GFL and 68% for actual textile effluent when compared to the individual one within 96 h. Speedy decolorization of Rubine GFL and actual textile effluent was observed due to the induction of oxido-reductive enzymes of the FD-SC consortium. Along with the significant reduction in the values of COD, BOD, ADMI, TSS, and TDS with 70, 64, 65, 41, and 52%, respectively, in experimental sets treated with FD-SC consortium. The biodegradation of Rubine GFL was confirmed with UV-Vis spectroscopy at the preliminary level, and then, metabolites formed after degradation were detected and identified by FTIR, HPLC, and GC-MS techniques. Also, decolorization of the dye was observed in the sections of the root cortex of Fimbristylis dichotoma. The toxicity of dye and metabolites formed after degradation was assessed by seed germination and bacterial count assay, where increased germination % and bacterial count from 31×107CFUs to 92 × 107 CFUs reflect the nontoxic nature of metabolites. Furthermore, the nontoxic nature of metabolites was confirmed by fish toxicity on Cirrhinus mrigala showed normal structures of fish gills and liver in the groups treated with FD-SC consortium proving the better tactic for biodegradation of dyes and textile effluent.
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Biodegradación Ambiental , Colorantes , Saccharomyces cerevisiae , Contaminantes Químicos del Agua , Colorantes/metabolismo , Colorantes/toxicidad , Saccharomyces cerevisiae/metabolismo , Contaminantes Químicos del Agua/metabolismo , Contaminantes Químicos del Agua/toxicidad , Aguas Residuales/microbiología , Aguas Residuales/química , Consorcios Microbianos , Compuestos Azo/metabolismo , Compuestos Azo/toxicidad , Residuos IndustrialesRESUMEN
INTRODUCTION: Previously published data are conflicting regarding the ability of tenecteplase versus alteplase to produce early recanalization of an intracranial large vessel occlusion. We compared the performance of each thrombolytic in a stroke network. METHODS: We queried our prospectively collected code stroke registry for basilar, internal carotid, or proximal middle cerebral artery occlusion patients treated with intravenous thrombolysis from 11/17/2021-9/16/2023. The primary outcome was early recanalization, defined using angiographic or clinical criteria. Secondary and safety outcomes included 90-day functional independence and symptomatic intracranial hemorrhage. A multivariable regression analysis was performed to determine independent associations with the primary outcome. RESULTS: 233 patients, with mean age 66.9 (16.6) years and median National Institutes of Health Stroke Scale score 15 (10-21), were included. One-hundred twenty-four of 233 (53.2%) patients were treated with alteplase while 109/233 (46.8%) were treated with tenecteplase. Endovascular thrombectomy was performed in 82% of subjects. Early recanalization rates were similar between the groups (alteplase 22.6%, tenecteplase 14.7%; p=0.14), as were rates of 90-day independent neurological function, symptomatic intracranial hemorrhage, and mortality. Patients with an internal carotid artery occlusion or with higher presenting stroke severity were less likely to achieve early recanalization. CONCLUSIONS: Tenecteplase and alteplase have similar rates of early recanalization, 90-day functional independence, and safety outcomes in large vessel occlusion patients. Occlusion site and stroke severity predict response to thrombolysis. Future studies may investigate other factors associated with a positive response to thrombolytics as expanded treatment indications are explored.
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BACKGROUND: PARP (poly(ADP-ribose) polymerase) inhibitors (PARPi) are now standard of care in metastatic castrate-resistant prostate cancer (mCRPC) patients with select mutations in DNA damage repair (DDR) pathways, but patients with ATM- and BRCA2 mutations may respond differently to PARPi. We hypothesized that differences may also exist in response to taxanes, which may inform treatment sequencing decisions. METHODS: mCRPC patients (N = 158) with deleterious ATM or BRCA2 mutations who received taxanes, PARPi, or both were retrospectively identified from 11 US academic centers. Demographic, treatment, and survival data were collected. Kaplan-Meier analyses were performed and Cox hazard ratios (HR) were calculated for progression-free survival (PFS) as well as overall survival (OS), from time of first taxane or PARPi therapy. RESULTS: Fifty-eight patients with ATM mutations and 100 with BRCA2 mutations were identified. Fourty-four (76%) patients with ATM mutations received taxane only or taxane before PARPi, while 14 (24%) received PARPi only or PARPi before taxane. Patients with ATM mutations had longer PFS when taxane was given first versus PARPi given first (HR: 0.74 [95% confidence interval [CI]: 0.37-1.50]; p = 0.40). Similarly, OS was longer in patients with ATM mutations who received taxane first (HR: 0.56 [CI: 0.20-1.54]; p = 0.26). Among patients with BRCA2 mutations, 51 (51%) received taxane first and 49 (49%) received PARPi first. In contrast, patients with BRCA2 mutations had longer PFS when PARPi was given first versus taxane given first (HR: 0.85 [CI: 0.54-1.35]; p = 0.49). Similarly, OS was longer in patients with BRCA2 mutations who received PARPi first (HR: 0.75 [CI: 0.41-1.37]; p = 0.35). CONCLUSIONS: Our retrospective data suggest differential response between ATM and BRCA2 mutated prostate cancers in terms of response to PARPi and to taxane chemotherapy. When considering the sequence of PARPi versus taxane chemotherapy for mCRPC with DDR mutations, ATM, and BRCA2 mutation status may be helpful in guiding choice of initial therapy.
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Inhibidores de Poli(ADP-Ribosa) Polimerasas , Neoplasias de la Próstata Resistentes a la Castración , Masculino , Humanos , Inhibidores de Poli(ADP-Ribosa) Polimerasas/farmacología , Inhibidores de Poli(ADP-Ribosa) Polimerasas/uso terapéutico , Estudios Retrospectivos , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/genética , Neoplasias de la Próstata Resistentes a la Castración/patología , Resultado del Tratamiento , Taxoides/uso terapéutico , Proteína BRCA2/genética , Proteínas de la Ataxia Telangiectasia Mutada/genéticaRESUMEN
BACKGROUND: To date, single-agent immune checkpoint inhibitor (CPI) therapy has proven to be ineffective against biomarker-unselected extrapulmonary poorly differentiated neuroendocrine carcinomas (EP-PDNECs). The efficacy of CPI in combination with chemotherapy remains under investigation. METHODS: Patients with advanced, progressive EP-PDNECs were enrolled in a two-part study of pembrolizumab-based therapy. In Part A, patients received pembrolizumab alone. In Part B, patients received pembrolizumab plus chemotherapy. PRIMARY ENDPOINT: objective response rate (ORR). Secondary endpoints: safety, progression-free survival (PFS) and overall survival (OS). Tumours were profiled for programmed death-ligand 1 expression, microsatellite-high/mismatch repair deficient status, mutational burden (TMB), genomic correlates. Tumour growth rate was evaluated. RESULTS: Part A (N = 14): ORR (pembrolizumab alone) 7% (95% CI, 0.2-33.9%), median PFS 1.8 months (95% CI, 1.7-21.4), median OS 7.8 months (95% CI, 3.1-not reached); 14% of patients (N = 2) had grade 3/4 treatment-related adverse events (TRAEs). Part B (N = 22): ORR (pembrolizumab plus chemotherapy) 5% (95% CI, 0-22.8%), median PFS 2.0 months (95% CI, 1.9-3.4), median OS 4.8 months (95% CI, 4.1-8.2); 45% of patients (N = 10) had grade 3/4 TRAEs. The two patients with objective response had high-TMB tumours. DISCUSSION: Treatment with pembrolizumab alone and pembrolizumab plus chemotherapy was ineffective in advanced, progressive EP-PDNECs. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT03136055.
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Carcinoma Neuroendocrino , Tumores Neuroendocrinos , Humanos , Anticuerpos Monoclonales Humanizados/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carcinoma Neuroendocrino/tratamiento farmacológico , Carcinoma Neuroendocrino/genética , Tumores Neuroendocrinos/tratamiento farmacológico , Supervivencia sin ProgresiónRESUMEN
BACKGROUND: Free oxygen radicals have been implicated in the pathogenesis of bronchopulmonary dysplasia (BPD) in preterm infants. Superoxide dismutase (SOD) is a naturally occurring enzyme which provides a defense against such oxidant injury. Providing supplementary SOD has been tested in clinical trials to prevent BPD in preterm infants. OBJECTIVES: To determine the efficacy and safety of SOD in the prevention and treatment of BPD on mortality and other complications of prematurity in infants at risk for, or having BPD. SEARCH METHODS: We searched CENTRAL, PubMed, Embase, and three trials registers on 22 September 2022 together with reference checking, citation searching and contact with study authors to identify additional studies. SELECTION CRITERIA: Randomized, quasi-randomized and cluster-randomized controlled trials (RCTs) where the participants were preterm infants who had developed, or were at risk of developing BPD, and who were randomly allocated to receive either SOD (in any form, by any route, any dose, anytime) or placebo, or no treatment. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were BPD defined as an oxygen requirement at 28 days, BPD defined as oxygen at 36 weeks' postmenstrual age, neonatal mortality, mortality prior to discharge, and BPD or death at 36 weeks' postmenstrual age. We reported risk ratio (RR) and risk difference (RD) with 95% confidence intervals (CIs) for the dichotomous outcomes. We used GRADE to assess certainty of evidence for each outcome. MAIN RESULTS: We included three RCTs (380 infants) on SOD administration in preterm infants at risk for BPD, and no studies in preterm infants with evolving BPD / early respiratory insufficiency. The evidence is very uncertain about the effect of SOD on BPD defined as an oxygen requirement at 28 days (RR 1.09, 95% CI 0.94 to 1.26; RD 0.06, 95% CI -0.05 to 0.16, 1 study, 302 infants; I2 for RR and RD not applicable), BPD defined as oxygen at 36 weeks' postmenstrual age (RR 0.96, 95% CI 0.72 to 1.29; RD -0.01, 95% CI -0.11 to 0.09, 2 studies, 335 infants; I2 for RR and RD = 0%), neonatal mortality (RR 0.98, 95% CI 0.57 to 1.68; RD -0.00, 95% CI -0.08 to 0.07, 2 studies, 335 infants; I2 for RR and RD = 0%), and mortality prior to discharge (RR 1.20, 95% CI 0.53 to 2.71; RD 0.04, 95% CI -0.14 to 0.23, 2 studies, 78 infants; I2 for RR and RD = 0%). No studies reported BPD or death at 36 weeks' postmenstrual age. The evidence is very uncertain about the effect of SOD on retinopathy of prematurity any stage (RR 0.95, 95% CI 0.78 to 1.15; RD -0.03, 95% CI -0.15 to 0.08, 2 studies, 335 infants; I2for RR = 0%, I2 for RD = 8%), and severe retinopathy of prematurity (ROP) (RR 0.97, 95% CI 0.57 to 1.65; RD -0.01, 95% CI -0.10 to 0.09, 1 study, 244 infants; I2 for RR and RD not applicable). No studies reported moderate to severe neurodevelopmental outcome at 18 to 24 months. Certainty of evidence was very low for all outcomes. We identified no ongoing trials. AUTHORS' CONCLUSIONS: The evidence is very uncertain about the effect of SOD on BPD defined as an oxygen requirement at 28 days, BPD defined as oxygen at 36 weeks' postmenstrual age, neonatal mortality and mortality prior to discharge compared to placebo. No studies reported BPD or death at 36 weeks' postmenstrual age and need for supplemental oxygen. The evidence is very uncertain about the effect of SOD on retinopathy of prematurity any stage and severe retinopathy of prematurity. No studies reported moderate to severe neurodevelopmental outcome at 18 to 24 months. The effects of SOD in preterm infants has not been reported in any trial in the last few decades, considering that the most recent trial on SOD in preterm infants was conducted in 1997/1998, and no new studies are ongoing. In the light of the limited available evidence, new data from preclinical and observational studies are needed to justify the conduction of new RCTs. Observational studies might report how SOD is administered, including indication, dose and association with relevant outcomes such as mortality, BPD and long-term neurodevelopment.
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Displasia Broncopulmonar , Retinopatía de la Prematuridad , Recién Nacido , Lactante , Humanos , Retinopatía de la Prematuridad/prevención & control , Displasia Broncopulmonar/prevención & control , Recien Nacido Prematuro , Oxígeno , Superóxido Dismutasa/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: Life expectancy (LE) differences within and between states by race/ethnicity have not been examined. OBJECTIVE: To estimate LE for selected race/ethnicity groups in states from 1990 to 2019. DESIGN: Cross-sectional time-series analysis. SETTING: United States. PARTICIPANTS: Deidentified death records and Census data were used to construct regression models with smoothed time series of mortality from 1990 to 2019. MEASUREMENTS: LE at birth, by sex and year, for subgroups of people reporting Hispanic, non-Hispanic Black, or non-Hispanic White race/ethnicity. RESULTS: Disparities in LE across states were 8.0 years for females and 12.2 years for males in 1990 and 7.9 years for females and 7.8 years for males in 2019. When race/ethnicity groups were accounted for, disparities across states were 20.7 years for females and 24.5 years for males in 1990, decreasing to 18.5 years for females and 23.7 years for males in 2019. Disparities across states increased within each race/ethnicity group between 1990 and 2019, with the largest increase for non-Hispanic White males and the smallest for Hispanic females. The disparity between race/ethnicity groups within states decreased for most of the 23 states with estimates for all 3 groups but increased for females in 7 states and males in 5 states. LIMITATION: Because of small sample size, LE was not estimated for 37 of 153 state-race/ethnicity groups. CONCLUSION: Disparity in LE across states was greater when race/ethnicity groups were considered. Disparities across all state-race/ethnicity groups in general have decreased over the past 3 decades. Within each race/ethnicity group, disparities across states have increased. Although racial/ethnic disparities decreased in most of the 23 states for which LE was estimated for all 3 groups, they increased for females in 7 states and males in 5 states. PRIMARY FUNDING SOURCE: National Heart, Lung, and Blood Institute.
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Negro o Afroamericano , Etnicidad , Estudios Transversales , Femenino , Hispánicos o Latinos , Humanos , Recién Nacido , Esperanza de Vida , Masculino , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: Virtual and augmented reality (AR) have become popular modalities for training myoelectric prosthesis control with upper-limb amputees. While some systems have shown moderate success, it is unclear how well the complex motor skills learned in an AR simulation transfer to completing the same tasks in physical reality. Limb loading is a possible dimension of motor skill execution that is absent in current AR solutions that may help to increase skill transfer between the virtual and physical domains. METHODS: We implemented an immersive AR environment where individuals could operate a myoelectric virtual prosthesis to accomplish a variety of object relocation manipulations. Intact limb participants were separated into three groups, the load control (CGLD; [Formula: see text]), the AR control (CGAR; [Formula: see text]), and the experimental group (EG; [Formula: see text]). Both the CGAR and EG completed a 5-session prosthesis training protocol in AR while the CGLD performed simple muscle training. The EG attempted manipulations in AR while undergoing limb loading. The CGAR attempted the same manipulations without loading. All participants performed the same manipulations in physical reality while operating a real prosthesis pre- and post-training. The main outcome measure was the change in the number of manipulations completed during the physical reality assessments (i.e. completion rate). Secondary outcomes included movement kinematics and visuomotor behavior. RESULTS: The EG experienced a greater increase in completion rate post-training than both the CGAR and CGLD. This performance increase was accompanied by a shorter motor learning phase, the EG's performance saturating in less sessions of AR training than the CGAR. CONCLUSION: The results demonstrated that limb loading plays an important role in transferring complex motor skills learned in virtual spaces to their physical reality analogs. While participants who did not receive limb loading were able to receive some functional benefit from AR training, participants who received the loading experienced a greater positive change in motor performance with their performance saturating in fewer training sessions.
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Amputados , Realidad Aumentada , Humanos , Amputados/rehabilitación , Extremidad Superior , Destreza Motora , Examen FísicoRESUMEN
Van der Waals (vdW) heterostructures continue to attract intense interest as a route of designing materials with novel properties that cannot be found in nature. Unfortunately, this approach is currently limited to only a few layers that can be stacked on top of each other. Here, we report a bulk vdW material consisting of superconducting 1H TaS2 monolayers interlayered with 1T TaS2 monolayers displaying charge density waves (CDW). This bulk vdW heterostructure is created by phase transition of 1T-TaS2 to 6R at 800 °C in an inert atmosphere. Its superconducting transition (Tc) is found at 2.6 K, exceeding the Tc of the bulk 2H phase. Using first-principles calculations, we argue that the coexistence of superconductivity and CDW within 6R-TaS2 stems from amalgamation of the properties of adjacent 1H and 1T monolayers, where the former dominates the superconducting state and the latter the CDW behavior.
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INTRODUCTION: The Critical Area Perfusion Score (CAPS) predicts functional outcomes in vertebrobasilar thrombectomy patients based on computed tomography perfusion (CTP) hypoperfusion. We compared CAPS to the clinical-radiographic Charlotte Large artery occlusion Endovascular therapy Outcome Score (CLEOS). METHODS: Acute basilar thrombosis patients from January 2017-December 2021 were included in this retrospective analysis from a health system's stroke registry. Inter-rater reliability was assessed for 6 CAPS raters. A logistic regression with CAPS and CLEOS as predictors was performed to predict 90-day modified Rankin Scale (mRS) score 4-6. Area under the curve (AUC) analyses were performed to evaluate prognostic ability. RESULTS: 55 patients, mean age 65.8 (± 13.1) years and median NIHSS score 15.55-24, were included. Light's kappa among 6 raters for favorable versus unfavorable CAPS was 0.633 (95% CI 0.497-0.785). Increased CLEOS was associated with elevated odds of a poor outcome (odds ratio (OR) 1.0010, 95% CI 1.0007-1.0014, p<0.01), though CAPS was not (OR 1.0028, 95% CI 0.9420-1.0676, p=0.93). An overall favorable trend was observed for CLEOS (AUC 0.69, 95% CI 0.54-0.84) versus CAPS (AUC 0.49, 95% CI 0.34-0.64; p=0.051). Among 85.5% of patients with endovascular reperfusion, CLEOS had a statistically higher sensitivity than CAPS at identifying poor 90-day outcomes (71% versus 21%, p=0.003). CONCLUSIONS: CLEOS demonstrated better predictive ability than CAPS for poor outcomes overall and in patients achieving reperfusion after basilar thrombectomy.
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Arteriopatías Oclusivas , Procedimientos Endovasculares , Accidente Cerebrovascular , Insuficiencia Vertebrobasilar , Humanos , Anciano , Resultado del Tratamiento , Estudios Retrospectivos , Reproducibilidad de los Resultados , Trombectomía/efectos adversos , Trombectomía/métodos , Arteria Basilar/diagnóstico por imagen , Arteriopatías Oclusivas/etiología , Procedimientos Endovasculares/efectos adversos , Procedimientos Endovasculares/métodos , Perfusión , Insuficiencia Vertebrobasilar/diagnóstico por imagen , Insuficiencia Vertebrobasilar/terapia , Insuficiencia Vertebrobasilar/etiologíaRESUMEN
The role of radiation therapy (RT) varies across hematologic malignancies (HM). Radiation oncology (RO) resident comfort with specific aspects of HM patient management is unknown. The International Lymphoma RO Group (ILROG) assessed resident HM training opportunities and interest in an HM away elective. RO residents (PGY2-5) in the Association of Residents in RO (ARRO) database (n = 572) were emailed an anonymous, web-based survey in January 2019 including binary, Likert-type scale (1 = not at all, 5 = extremely, reported as median [interquartile range]), and multiple-choice questions. Of 134 resident respondents (23%), 86 (64%) were PGY4/5 residents and 36 (27%) were in larger programs (≥ 13 residents). Residents reported having specialized HM faculty (112, 84%) and a dedicated HM rotation (95, 71%). Residents reported "moderate" preparedness to advocate for RT in multidisciplinary conferences (3 [2-3]); make HM-related clinical decisions (3 [2-4]); and critique treatment planning (3 [2-4]). They reported feeling "moderately" to "quite" prepared to contour HM cases (3.5 [3-4]) and "quite" prepared to utilize the PET-CT five-point scale (4 [3-5]). Overall, residents reported feeling "moderately" prepared to treat HM patients (3 [2-3]); 24 residents (23%) felt "quite" or "extremely" prepared. Sixty-six residents (49%) were potentially interested in an HM away elective, commonly to increase comfort with treating HM patients (65%). Therefore, HM training is an important component of RO residency, yet a minority of surveyed trainees felt quite or extremely well prepared to treat HM patients. Programs should explore alternative and additional educational opportunities to increase resident comfort with treating HM patients.
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Neoplasias Hematológicas , Internado y Residencia , Linfoma , Oncología por Radiación , Humanos , Oncología por Radiación/educación , Tomografía Computarizada por Tomografía de Emisión de Positrones , Encuestas y Cuestionarios , Neoplasias Hematológicas/radioterapiaRESUMEN
Regulatory T cells (Tregs) modulate alloimmune responses and may facilitate minimization or withdrawal of immunosuppression posttransplant. Current approaches, however, rely on complex ex vivo Treg expansion protocols. Herein, we explore endogenous in vivo Treg expansion through antibody-mediated agonistic stimulation of the tumor necrosis factor receptor superfamily member 25 (TNFRSF25) pathway and its potential to prolong graft survival in a mouse model of islet allotransplantation. C57BL/6 male mice were treated with a single dose of TNFRSF25 agonistic antibodies (4C12 or mPTX-35) or IgG control. Diabetes was induced using streptozotocin. Four days later, flow cytometry was completed to corroborate Treg expansion, and 500 islets (CBA/J male mice) were transplanted. Glycemia was assessed thrice weekly until rejection/endpoint. Early intra-graft Treg infiltration was assessed 36 h posttransplant. TNFRSF25 antibodies enabled pronounced Treg expansion and treated mice had significantly prolonged graft survival compared with controls (p < .001). Additionally, the degree of Treg expansion significantly correlated with graft survival (p < .001). Immunohistochemistry demonstrated marked Treg infiltration in long-term surviving grafts; intra-graft Treg infiltration occurred early posttransplant. In conclusion, a single dose of TNFRSF25 antibodies enabled in vivo Treg expansion, which promotes prolonged graft survival. TNFRSF25-mediated in vivo Treg expansion could contribute to achieving lasting immunological tolerance in organ transplantation.
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Trasplante de Islotes Pancreáticos , Aloinjertos , Animales , Rechazo de Injerto/etiología , Supervivencia de Injerto , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Endogámicos CBA , Linfocitos T ReguladoresRESUMEN
Nitrate is an important nutrient and a key signalling molecule for plant development. A number of transcription factors involved in the response to nitrate and their regulatory mechanisms have been identified. However, little is known about the transcription factors involved in nitrate sensing and their regulatory mechanisms among crop plants. In this study, we identified functions of a nitrate-responsive miR444:MADS-box transcription factor OsMADS27 module and its downstream targets mediating rice root growth and stress responses. Transgenic rice plants expressing miR444 target mimic improved rice root growth. Although miR444 has the potential to target multiple genes, we identified OsMADS27 as the major miR444 target that regulates the expression of nitrate transporters, as well as several key genes including expansins, and those associated with auxin signalling, to promote root growth. In agreement with this, overexpression of miRNA-resistant OsMADS27 improved root development and tolerance to abiotic stresses, while its silencing suppressed root growth. OsMADS27 mediated robust stress tolerance in plants through its ability to bind to the promoters of specific stress regulators, as observed in ChIP-seq analysis. Our results provide evidence of a nitrate-dependent miR444-OsMADS27 signalling cascade involved in the regulation of rice root growth, as well as its surprising role in stress responses.
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MicroARNs/genética , Oryza , Regulación de la Expresión Génica de las Plantas , Nitratos/metabolismo , Oryza/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Raíces de Plantas/metabolismo , Plantas Modificadas Genéticamente/genética , Plantas Modificadas Genéticamente/metabolismo , Factores de Transcripción/metabolismoRESUMEN
Biallelic pathogenic variants in phosphopantothenoylcysteine synthetase, PPCS, are a rare cause of a severe early-onset dilated cardiomyopathy with high morbidity and mortality. To date, only five individuals with PPCS-mutations have been reported. Here, we report a female infant who presented in the neonatal period with hypotonia, a necrotizing myopathy with intermittent rhabdomyolysis and other extracardiac manifestations before developing a progressive and ultimately fatal dilated cardiomyopathy. Gene agnostic trio genome sequencing revealed two rare variants in the PPCS [MIM: 609853] in trans, a previously reported pathogenic c.320_334del p. (Pro107_Ala111del) variant, and a c.613-3C>G intronic variant of uncertain significance. Functional studies confirmed the likely pathogenicity of this variant. Our case provides clinical and histopathological evidence for an associated neuromuscular phenotype not previously recognized and expands the evolving phenotypic spectrum of PPCS-related disorders. We also performed a literature search of all previously published cases and summarize the common features.
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Cardiomiopatía Dilatada , Cardiomiopatía Dilatada/genética , Femenino , Humanos , MutaciónRESUMEN
The properties of water at interfaces have long been known to differ from those of bulk water in many distinctive ways. More recently, specific confinement effects different from mere interfacial effects have been discovered upon enclosing water in very narrow cylindrical pores and planar surfaces as offered by nanotubes and slit pores, respectively. Using experimental and theoretical THz spectroscopy, we elucidate nanoconfinement effects on the H-bond network of stratified water lamellae that are hosted within graphene-based two-dimensional pores. Characteristic confinement-induced changes of the THz response are traced back to the level of structural dynamics, notably distinct resonances due to intralayer and interlayer H-bonds at correspondingly low and high intermolecular stretching frequencies and impact of dangling (free) OH bonds at the water-graphene interface that enormously broaden the librational band in sufficiently narrow pores. The interplay of these molecular effects causes characteristic changes of the THz lineshape upon nanoconfining water.
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The solar thermochemical CO2 splitting (CDS) is scrutinized via a redox ZnO/Zn cycle. The second law efficiency analysis is carried out by acquiring the required thermodynamic data from HSC Chemistry software. The main focus of this study is to explore the influence of reduction temperature (Tred), molar flow rate of inert sweep gas (nËinert), and energy required for the gas separation on the solar-to-fuel energy conversion efficiency (ηsolar-to-fuel) of the ZnO/Zn cycle. All the calculations are conducted at a constant gas-to-gas heat recovery effectiveness (εgg) equal to 0.5. nËinert required is recorded to be too high (5050 mol/s) at Tred equal to 1500 K and moderately low (15 mol/s) for Tred equal to 2000 K. The amount of thermal energy required to heat the inert/O2 gas mixture (from CDS temperature to separator-1 temperature) and inert sweep gas (from separator-1 temperature to reduction temperature) has a significant impact on the total thermal energy requirement of the cycle (QËTC). The rise in Tred from 1500 K to 2000 K shows a considerable decline in QËTC from 77417.5 kW to 1161.8 kW, respectively. Consequently, the highest ηsolar-to-fuel (17.0%) is recorded for Tred equal to 2000 K.
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OBJECTIVES: We sought to optimize functional outcome prediction for large artery occlusion (LAO) patients treated with endovascular thrombectomy (EVT). MATERIALS AND METHODS: Patients presenting with an anterior circulation LAO treated with EVT from November 2016-July 2020 were included from a health system's code stroke registry. Data were separated into training and validation cohorts using a simple random sampling method. Logistic regression analysis was used to identify pre-intervention prognostic factors independently associated with 90-day modified Rankin score 4-6 in the training cohort. The model was tested in the validation cohort and compared to previously reported scales using Area Under Curve (AUC) analyses. RESULTS: 646 total patients were included. The Charlotte Large artery occlusion Endovascular therapy Outcome Score, CLEOS = (5 x Age) + (10 x NIHSS) + Glucose - (150 x Cerebral Blood Volume Index). CLEOS was associated with an increased odds of poor 90-day outcome (per 1-point increase, OR 1.008, 95% CI 1.006-1.010, p < 0.0001) and performed better than Stroke Prognostication using Age and National Institute of Health Stroke Scale - 100 (AUC 0.62, p < 0.0001) and Houston Intra-Arterial Therapy 2 (AUC 0.70, p < 0.0063), with a trend observed versus Pittsburgh Response to Endovascular therapy (AUC 0.72, p = 0.0884), in the combined analysis of the derivation and validation cohorts. CLEOS ≥ 700 was not associated with a lower risk of poor outcome despite excellent endovascular reperfusion. CONCLUSIONS: CLEOS can predict poor 90-day outcomes after thrombectomy and help risk stratify patients based on the degree of revascularization after EVT.
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Arteriopatías Oclusivas , Procedimientos Endovasculares , Accidente Cerebrovascular , Arterias , Procedimientos Endovasculares/efectos adversos , Procedimientos Endovasculares/métodos , Humanos , Pronóstico , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/terapia , Trombectomía/efectos adversos , Trombectomía/métodos , Resultado del TratamientoRESUMEN
Biopolymeric nanoparticulate systems hold favorable carrier properties for active delivery. The enhancement in the research interest in alginate formulations in biomedical and pharmaceutical research, owing to its biodegradable, biocompatible, and bioadhesive characteristics, reiterates its future use as an efficient drug delivery matrix. Alginates, obtained from natural sources, are the colloidal polysaccharide group, which are water-soluble, non-toxic, and non-irritant. These are linear copolymeric blocks of α-(1â4)-linked l-guluronic acid (G) and ß-(1â4)-linked d-mannuronic acid (M) residues. Owing to the monosaccharide sequencing and the enzymatically governed reactions, alginates are well-known as an essential bio-polymer group for multifarious biomedical implementations. Additionally, alginate's bio-adhesive property makes it significant in the pharmaceutical industry. Alginate has shown immense potential in wound healing and drug delivery applications to date because its gel-forming ability maintains the structural resemblance to the extracellular matrices in tissues and can be altered to perform numerous crucial functions. The initial section of this review will deliver a perception of the extraction source and alginate's remarkable properties. Furthermore, we have aspired to discuss the current literature on alginate utilization as a biopolymeric carrier for drug delivery through numerous administration routes. Finally, the latest investigations on alginate composite utilization in wound healing are addressed.
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Alginatos , Polímeros , Alginatos/química , Biopolímeros , Ácido Glucurónico/química , Ácidos Hexurónicos/química , Cicatrización de HeridasRESUMEN
INTRODUCTION: Patients presenting with large ischemic core volumes (LICVs) on computed tomography perfusion (CTP) are at high risk for poor functional outcomes. We sought to identify predictors of outcome in patients with an internal carotid artery (ICA) or middle cerebral artery (MCA) occlusion and LICV. METHODS: A large healthcare system's prospectively collected code stroke registry was utilized for this retrospective analysis of patients presenting within 6 hours with at least 50 ml of CTP reduced relative cerebral blood flow (CBF) < 30%. A multivariable logistic regression model was constructed to identify independent predictors (p < 0.05) of poor discharge outcome (modified Rankin scale score 4-6). RESULTS: Over a 38-month period, we identified 104 patients meeting inclusion criteria, with a mean age of 65.4 ± 16.2 years, median presenting National Institutes of Health Stroke Scale score 20 (IQR 16-24), median ischemic core volume (CBF < 30%) 82 ml (IQR 61-118), and median mismatch volume 80 ml (IQR 56-134). Seventy-five patients (72.1%) had a discharge modified Rankin scale score of 4-6. Sixty-six of 104 (63.5%) patients were treated with endovascular thrombectomy (EVT). In the multivariable regression model, EVT (OR 0.303; 95% CI 0.080-0.985; p = 0.049) and lower blood glucose (per 1-point increase, OR 1.014; 95% CI 1.003-1.030; p = 0.030) were independently protective against poor discharge outcome. CONCLUSIONS: EVT is independently associated with a reduced risk of poor functional outcome in patients presenting within 6 hours with ICA or MCA occlusions and LICV.