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The purpose of the study was to examine education doctoral student perspectives on their experience of enrolling in a fully online EdD program during a global pandemic and achieving career advancement during their enrollment through the lens of transformative learning theory. A qualitative study of 12 participants was conducted to examine in what ways the pandemic influenced their decision to enroll in an online doctorate program, in ways their thinking progressed throughout the program, and the factors affecting their decision to take on a career advancement while enrolled in the program. The findings indicate that there were elements of transformative learning that occurred for many of the participants. Faculty teaching in doctorate programs are encouraged to explore how they might foster transformative learning experiences for their students.

Deficits in memory performance have been linked to a wide range of neurological and neuropsychiatric conditions. While many studies have assessed the memory impacts of individual conditions, this study considers a broader perspective by evaluating how memory recall is differentially associated with nine common neuropsychiatric conditions using data drawn from 55 international studies, aggregating 15,883 unique participants aged 15-90. The effects of dementia, mild cognitive impairment, Parkinsons disease, traumatic brain injury, stroke, depression, attention-deficit/hyperactivity disorder (ADHD), schizophrenia, and bipolar disorder on immediate, short-, and long-delay verbal learning and memory (VLM) scores were estimated relative to matched healthy individuals. Random forest models identified age, years of education, and site as important VLM covariates. A Bayesian harmonization approach was used to isolate and remove site effects. Regression estimated the adjusted association of each clinical group with VLM scores. Memory deficits were strongly associated with dementia and schizophrenia (p < 0.001), while neither depression nor ADHD showed consistent associations with VLM scores (p > 0.05). Differences associated with clinical conditions were larger for longer delayed recall duration items. By comparing VLM across clinical conditions, this study provides a foundation for enhanced diagnostic precision and offers new insights into disease management of comorbid disorders.

This essay presents the reflections of four Education Doctorate (EdD) students on the pilot testing strategies used during an online research methods course. Rigorous questionnaire and interview development skills are challenging to acquire. Pilot testing is an under-researched stage of instrument design, yet it is crucial to ensure validity and reliability, reduce bias, and psychologically prepare researchers for data collection. A structured, multi-step pilot testing process led to the collective development of stronger scholar-practitioner identities, the use of innovative synchronous/asynchronous methods during COVID-19 and increased academic rigor. These reflections demonstrate how several types of pilot testing can support the development of rigorous data collection instruments and prepare post-graduate students for the psychological and technical challenges they may encounter in future research.

This essay highlights the value of an applied methodology course in program evaluation in the education doctorate program by exploring several benefits that it offers to enhance a doctoral student's ability to solve complex problems of practice. Observations and recommendations are made based on designing and teaching two cohorts of EdD students in a program evaluation course. Improvement science is referenced throughout to highlight how the two may complement each other, not to place a higher value on one or the other. How and where program evaluation and improvement science appear to have possible areas of overlap, along with a brief overview of the major differences, are discussed. The author maintains that both program evaluation and improvement constitute a tremendous capacity to provide the ideas, tools, and approaches to prepare students to be the change agents they hope to aspire to be in their present and future roles as scholarly practitioners.

INTRODUCTION: Despite numerous investigations into the impact of drugs/probiotics on the gut microbiota composition in Familial Mediterranean Fever (FMF) patients, the question as to whether there exists a significant bacterial diversity(ies) independent of the placebo effect that can be reliably considered in clinical and nutritional trials remains unresolved. METHODS: This study represents the in augural analysis of the placebos influence on the gut microbiota of both healthy individuals and FMF afflicted men, utilizing previously collected data from PhyloChip™ DNA microarray experiments. A total of 15 healthy and 15 FMF male volunteers, aged 18 to 50, participated in this partially randomized placebo trial, which is accessible through the GEO Series accession number GSE111835. RESULTS AND DISCUSSION: Key findings from current investigations include i. the anticipated divergence in gut bacteria resistance to placebo between healthy and FMF individuals, ii. the minor impact of placebo on gut bacterial diversities in healthy individuals, with Enterobacteriaceae diversities identified as placebo-resistant among healthy gut bacteria, and iii. the comprehensive influence of placebo on all bacterial phyla in the gut microbiome of FMF patients, extending to nearly all bacterial genera, except for the resilience of gut Akkermansia muciniphila spp. to placebo in FMF patients. This study underscores the susceptibility of Faecalibacterium, Blautia, and Clostridium genera to placebo. Consequently, this investigation holds significance for the proper design of placebo-controlled trials and establishes a foundation for further exploration of the gut-brain axis. Furthermore, it contributes valuable insights to discussions regarding proposals for probiotic therapies, particularly focusing on Faecalibacterium spp., Blautia spp., and Clostridium spp.

Abstract Objective Locomotion is an automated voluntary movement sustained by coordinated neural synchronization across a distributed brain network. The cerebral cortex is central for adapting the locomotion pattern to the environment and alterations of cortical network dynamics can lead to gait impairments. Gait problems are a common symptom with a still unclear pathophysiology and represent an unmet therapeutical need in Parkinson's disease. Little is known about the cortical network dynamics of locomotor control in these patients. Methods We studied the cortical basis of parkinsonian gait by combining metabolic brain imaging with high‐density EEG recordings and kinematic measurements performed at rest and during unperturbed overground walking. Results We found significant changes in functional connectivity between frontal, sensorimotor, and visuomotor cortical areas during walking as compared to resting. Specifically, hypokinetic gait was associated with poor information flow from the supplementary motor area (SMA) to precuneus and from calcarine to lingual gyrus, as well as high information flow from calcarine to cuneus. Interpretation Our findings support a role for visuomotor integration processes in PD‐related hypokinetic gait and suggest that reinforcing visual information may act as a compensatory strategy to allow SMA‐mediated feedforward locomotor control in PD.

Background and Purpose The management of acute ischemic stroke (AIS) due to distal medium vessel occlusion (DMVO) remains uncertain, particularly in comparing the effectiveness of intravenous thrombolysis (IVT) plus mechanical thrombectomy (MT) versus IVT alone. This study aimed to evaluate the safety and efficacy in DMVO patients treated with either MT-IVT or IVT alone. Methods This multinational study analyzed data from 37 centers across North America, Asia, and Europe. Patients with AIS due to DMVO were included, with data collected from September 2017 to July 2023. The primary outcome was functional independence, with secondary outcomes including mortality and safety measures such as types of intracerebral hemorrhage. Results The study involved 1,057 patients before matching, and 640 patients post-matching. Functional outcomes at 90 days showed no significant difference between groups in achieving good functional recovery (modified Rankin Scale 0–1 and 0–2), with adjusted odds ratios (OR) of 1.21 (95% confidence interval [CI] 0.81 to 1.79; P=0.35) and 1.00 (95% CI 0.66 to 1.51; P>0.99), respectively. Mortality rates at 90 days were similar between the two groups (OR 0.75, 95% CI 0.44 to 1.29; P=0.30). The incidence of symptomatic intracerebral hemorrhage was comparable, but any type of intracranial hemorrhage was significantly higher in the MT-IVT group (OR 0.43, 95% CI 0.29 to 0.63; P

Non-alcoholic fatty liver disease (NAFLD) has emerged as a significant global health issue. The condition is closely linked to metabolic dysfunctions such as obesity and type 2 diabetes. The gut–liver axis, a bidirectional communication pathway between the liver and the gut, plays a crucial role in the pathogenesis of NAFLD. This review delves into the mechanisms underlying the gut–liver axis, exploring the influence of gut microbiota, intestinal permeability, and inflammatory pathways. This review also explores the potential therapeutic strategies centered on modulating gut microbiota such as fecal microbiota transplantation; phage therapy; and the use of specific probiotics, prebiotics, and postbiotics in managing NAFLD. By understanding these interactions, we can better comprehend the development and advancement of NAFLD and identify potential therapeutic targets.

Abstract We discuss the flat space limit of AdS using the momentum space representation of CFT correlators. The flat space limit involves sending the AdS radius and the dimensions of operators dual to massive fields to infinity while also scaling appropriately the sources of the dual operators. In this limit, d-dimensional CFT correlators become (d + 1)-dimensional scattering amplitudes. We exemplify our discussion with the computation of the flat-space limit of the CFT 3-point function of a conserved current, a non-conserved charged vector operator and its conjugate. The flat-space limit should yield the scattering amplitude of an Abelian gauge field with two massive vector fields. This scattering amplitude computes the electromagnetic form factors of the electromagnetic current in a spin-1 state, and these form factors encode the electromagnetic properties of the massive vector field (charge, magnetic moment and quadruple moment). In terms of the CFT, the flat-space limit amounts to zooming in the infrared region of the triple-K integrals that determine the 3-point function, while also scaling to infinity the order of (some of) the Bessel functions that feature in the triple-K integrals. In this limit the triple-K integral becomes proportional to the energy-preserving delta function, and the flat space limit correctly yields the corresponding flat space scattering amplitude in complete detail.

Abstract We report the long-term results of a randomized trial (GITMO, AML-R2), comparing 1:1 the combination of busulfan and cyclophosphamide (BuCy2, n = 125) and the combination of busulfan and fludarabine (BuFlu, n = 127) as conditioning regimen in acute myeloid leukemia patients (median age 51 years, range 40–65) undergoing allogeneic hematopoietic stem cell transplantation. With a median follow-up of 6 years, significantly better non-relapse mortality (NRM) was confirmed in BuFlu recipients, which is sustained up to 4 years after transplant (10% vs. 20%, p = 0.0388). This difference was higher in patients older than 51 years (11% in BuFlu vs. 27% in BuCy2, p = 0.0262). The cumulative incidence of relapse, which was the first cause of death in the entire study population, did not differ between the two randomized arms. Similarly, the leukemia-free survival (LFS) and overall survival (OS) were not different in the two cohorts, even when stratifying patients per median age. Graft-and relapse-free survival (GRFS) in BuFlu arm vs. the BuCy2 arm was 25% vs. 20% at 4 years and 20% vs. 17% at 10 years. Hence, the benefit gained by NRM reduction is not offsets by an increased relapse. Leukemia relapse remains a major concern, urging the development of new therapeutic approaches.

Abstract Introduction Climate change is contributing to increase the frequency and severity of climate disasters in Mozambique, leading, since 2019, to extensive damage to infrastructure and displacement 1.3 million people. Aim of this study is to evaluate baseline preparedness to vector-borne and water-borne infections among households and internally displaced people exposed to climate disasters in Mozambique. Methods This was a cross-sectional, community-based survey assessing the preparedness to infectious diseases outbreaks among people exposed to climate disasters in six districts in Mozambique. Structured form was delivered via face-to-face between October 15th and November 7th, 2022. Study outcome was defined as a seven-point score of preparedness to infectious disease outbreaks. Multivariable analysis of the score was conducted using Conway-Maxwell-Poisson regression. Results This study included 2,140 households and 11,239 people, with IDPs accounting for 30% of them. Overall, 1,186 (55.4%) households were overcrowded. Median score of preparedness was 3 points (IQR 2–4). At multivariable analyses, districts with low preparedness were Montepuez and Mueda. Higher preparedness was associated with family planning (p

Abstract The prevalence of multidrug resistant (MDR) bacterial infections continues to rise as the development of antibiotics needed to combat these infections remains stagnant. MDR enterococci are a major contributor to this crisis. A potential therapeutic approach for combating MDR enterococci is bacteriophage (phage) therapy, which uses lytic viruses to infect and kill pathogenic bacteria. While phages that lyse some strains of MDR enterococci have been identified, other strains display high levels of resistance and the mechanisms underlying this resistance are poorly defined. Here, we use a CRISPR interference (CRISPRi) screen to identify a genetic locus found on a mobilizable plasmid from Enterococcus faecalis involved in phage resistance. This locus encodes a putative serine recombinase followed by a Type IV restriction enzyme (TIV-RE) that we show restricts the replication of phage phi47 in vancomycin-resistant E. faecalis. We further find that phi47 evolves to overcome restriction by acquiring a missense mutation in a TIV-RE inhibitor protein. We show that this inhibitor, termed type IV restriction inhibiting factor A (tifA), binds and inactivates diverse TIV-REs. Overall, our findings advance our understanding of phage defense in drug-resistant E. faecalis and provide mechanistic insight into how phages evolve to overcome antiphage defense systems.

Abstract Human RAD52 (RAD52) is a DNA-binding protein involved in many DNA repair mechanisms and genomic stability maintenance. In the last few years, this protein was discovered to be a promising novel pharmacological target for anticancer strategies. Although the interest in RAD52 has exponentially grown in the previous decade, most information about its structure and mechanism still needs to be elucidated. Here, we report the 2.2 Å resolution cryo-EM reconstruction of the full-length RAD52 (FL-RAD52) protein. This allows us to describe the hydration shell of the N-terminal region of FL-RAD52, which is structured in an undecamer ring. Water molecules coordinate with protein residues to promote stabilization inside and among the protomers and within the inner DNA binding cleft to drive protein-DNA recognition. Additionally, through a multidisciplinary approach involving SEC-SAXS and computational methods, we comprehensively describe the highly flexible and dynamic organization of the C-terminal portion of FL-RAD52. This work discloses unprecedented structural details on the FL-RAD52, which will be critical for characterizing its mechanism of action and inhibitor development, particularly in the context of novel approaches to synthetic lethality and anticancer drug discovery.

La suspensión de la presencialidad escolar durante el período de confinamiento por motivo de la pandemia por COVID 19 alteró la vida cotidiana de las familias uruguayas y generó desafíos para el acompañamiento educativo de las infancias. Este artículo analiza las experiencias de las familias en este período, haciendo énfasis en la organización de los cuidados y las actividades de acompañamiento y sostén del tránsito escolar de niñas y niños, identificando obstáculos y oportunidades. Se trata de un estudio cualitativo, que utilizó como técnica inicial, un cuestionario autoadministrado que permitió identificar aspectos de las experiencias de las familias tomados como guía para la realización de grupos de discusión. Aquí se comparten los resultados del cuestionario online respondido por un total de 278 referentes familiares de niños y niñas que cursaron de 1ero a 3er año escolar en instituciones públicas durante los años 2020 y 2021. Como principales conclusiones se destaca que las familias participantes perciben como satisfactorio el acompañamiento realizado. Las dificultades halladas se relacionan principalmente con el tipo de propuesta educativa y modo de comunicación establecido con las maestras, las condiciones materiales del hogar (disponibilidad de dispositivos electrónicos, conectividad, espacio físico, etc.), disponibilidad de tiempo, afectiva y cognitiva para enseñar o motivar al aprendizaje de sus hijos e hijas. Rescatando la oportunidad que significó compartir más tiempo con los niños y niñas, se presenta la preocupación por manifestaciones de malestar físico y psíquico ante la situación de distancia de la cotidianeidad escolar y sus exigencias.

Abstract Diatoms are microalgae that live in marine and freshwater environments and are responsible for about 20% of the world’s carbon fixation. Population dynamics of these cells is finely regulated by intricate signal transduction systems, in which oxylipins are thought to play a relevant role. These are oxygenated fatty acids whose biosynthesis is initiated by a lipoxygenase enzyme (LOX) and are widely distributed in all phyla, including diatoms. Here, we present a de novo transcriptome obtained from the RNA-seq performed in the diatom species Pseudo-nitzschia arenysensis, using both a wild-type and a LOX-silenced strain, which will represent a reliable reference for comparative analyses within the Pseudo-nitzschia genus and at a broader taxonomic scale. Moreover, the RNA-seq data can be interrogated to go deeper into the oxylipins metabolic pathways.

Abstract Importance Large-scale estimates of bronchopulmonary dysplasia (BPD) are warranted for adequate prevention and treatment. However, systematic approaches to ascertain rates of BPD are lacking. Objective To conduct a systematic review and meta-analysis to assess the prevalence of BPD in very low birth weight (≤ 1,500 g) or very low gestational age (

Mesolimbic nicotinic acetylcholine receptor (nAChRs) activation is necessary for nicotine reinforcement behavior, but it is unknown whether selective activation of nAChRs in the dopamine (DA) reward pathway is sufficient to support nicotine reinforcement. In this study, we tested the hypothesis that activation of β2-containing (β2*) nAChRs on VTA neurons is sufficient for intravenous nicotine self-administration (SA). We expressed β2 nAChR subunits with enhanced sensitivity to nicotine (referred to as β2Leu9'Ser) in the VTA of male Sprague Dawley (SD) rats, enabling very low concentrations of nicotine to selectively activate β2* nAChRs on transduced neurons. Rats expressing β2Leu9'Ser subunits acquired nicotine SA at 1.5 μg/kg/infusion, a dose too low to support acquisition in control rats. Saline substitution extinguished responding for 1.5 μg/kg/inf, verifying that this dose was reinforcing. β2Leu9'Ser nAChRs also supported acquisition at the typical training dose in rats (30 μg/kg/inf) and reducing the dose to 1.5 μg/kg/inf caused a significant increase in the rate of nicotine SA. Viral expression of β2Leu9'Ser subunits only in VTA DA neurons (via TH-Cre rats) also enabled acquisition of nicotine SA at 1.5 μg/kg/inf, and saline substitution significantly attenuated responding. Next, we examined electrically-evoked DA release in slices from β2Leu9'Ser rats with a history of nicotine SA. Single-pulse evoked DA release and DA uptake rate were reduced in β2Leu9'Ser NAc slices, but relative increases in DA following a train of stimuli were preserved. These results are the first to report that β2* nAChR activation on VTA neurons is sufficient for nicotine reinforcement in rats.

Cognitive states like motor imagery (MI; simulating actions without overtly executing them) share a close correspondence with action execution, and hence, activate the motor system in a similar way. However, as people age, reduction in specific cognitive abilities like motor action simulation and action planning/prediction are commonly experienced. The present study examined the effect of visual–spatial processing for both typical and challenging upper-limb movements using the Hand Laterality Judgment Task (HLJT), in which participants were asked to judge whether the depicted hand is a left or right hand. Several main findings emerged: (1) Compared to younger adults, older adults exhibited slower responses and greater error rates in both Experiment 1 and 2. This suggests that visual–spatial transformations undergo alterations with age; (2) Older adults displayed higher error rates with realistic hands at both back and palm viewpoints of the hands compared to younger adults. However, this pattern did not hold for response times; (3) Participants responded faster to medial hand orientations (i.e., closer to the midline of the body) compared to lateral hand orientations (i.e., farther from the midline of the body) for palm-views in both Experiment 1 and Experiment 2. Given that we observed better performance on medial orientations compared to lateral orientations, this suggests that participants follow the same motor rules and biomechanical constraints of the represented movement. Novel information is provided about differences in individuals’ use of strategies (visual vs. motor imagery) to solve the HLJT for both mannequin and real hands.