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The ability to recognize and name the sounds of alphabet letters is a crucial prerequisite for students as they embark on their journey to learn how to read. Regrettably, some children face significant challenges in this area. In this single-case multiple baseline study, we utilized mnemonic pictures to facilitate the memorization of the grapheme-phoneme correspondence of ten target letters. Our aim was to empower four struggling first-grade students to quickly and confidently retrieve this information. The results reveal that the students significantly benefited from the intervention. Furthermore, the approach was perceived as attractive and helpful by both the four children and their teacher. The study concludes by reflecting on its limitations and discussing potential implications and future avenues of research.

This study examined the impact of journals that focus on supporting individuals with learning disabilities (LDs). We analyzed the visibility of 360 articles that appeared in seven scholarly outlets (ILD, IJRLD, JLD, LDCJ, LDMJ, LDQ, and LDRP) over a one-year period (2022). Using a two-year Google-based Journal Impact Factor (two-year GJIF), the Journal of Learning Disabilities (JLD) was found to have the greatest impact as measured by the number of citations. JLD articles published in 2020-2021 were referenced an average of 9.24 times in 2022, compared to the remaining journals, which were referenced between 1.45 and 6.00 times. However, the variation in citations for different papers was enormous, even within specific journals (e.g., one JLD study reached 61 citations, while others were not even quoted once). It is essential that key findings about how to effectively support individuals with LDs are disseminated as widely as feasible. Only then will it be possible for them to reach their potential and find their place in the mainstream of society.

Abstract Several indices have been devised to quantify a person’s stability from its gait pattern during overground walking. However, clinical interpretation of the indices is difficult because the link between being stable and adopting a mechanically stable gait pattern may not be straightforward. This is particularly true for one of these indices, the margin of stability, for which opposite interpretations are available in the literature. We collected overground walking data in two groups of 20 children, with unilateral cerebral palsy (CP) and typically developing (TD), for two conditions, on flat and on uneven grounds (UG). We postulated that TD children were more stable during gait than children with CP and that both groups were more stable on flat compared to UG. We explored the coherent association between several indices and the two postulates to clarify clinical interpretation. Our results showed that increased margin of stability, increased amplitude of the whole-body angular momentum, decreased duration of single limb support, increased variability (gait kinematics, step length, and step width) were associated with reduced stability for both postulates. However, results for the margin of stability were paradoxical between the sides in the CP group where small margin of stability was indicative of a fall forward strategy on the affected side rather than improved stability. Whole-body angular momentum and duration of single limb support appeared as the most sensitive indices. However, walking speed influenced these and would need to be considered when comparing groups of different walking speed.

The continuous technological development of electronic devices and the introduction of new materials lead to ever greater demands on the fabrication of semiconductor heterostructures and their characterization. This work focuses on optimizing Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS) depth profiles of semiconductor heterostructures aiming at a minimization of measurement-induced profile broadening. As a model system, a state-of-the-art Molecular Beam Epitaxy (MBE) grown multilayer homostructure consisting of n a t Si/ 28 Si bilayers with only 2 nm in thickness is investigated while varying the most relevant sputter parameters. Atomic concentration-depth profiles are determined and an error function based description model is used to quantify layer thicknesses as well as profile broadening. The optimization process leads to an excellent resolution of the multilayer homostructure. The results of this optimization guide to a ToF-SIMS analysis of another MBE grown heterostructure consisting of a strained and highly purified 28 Si layer sandwiched between two Si 0.7 Ge 0.3 layers. The sandwiched 28 Si layer represents a quantum well that has proven to be an excellent host for the implementation of electron-spin qubits. [ABSTRACT FROM AUTHOR]

Introduction Obesity has been causing worldwide concern with the increase in its cases where the population fails to maintain healthy habits. Furthermore, insulin resistance, hyperinsulinemia, and dyslipidemia associated with obesity [...], The beneficial effects of high-fat low-carbohydrate (HFLC) diets on glucose metabolism have been questioned and their effects on liver metabolism are not totally clear. The aim of this work was to investigate the effects of an HFLC diet under different energy conditions on glucose homeostasis, fatty liver development, and hepatic gluconeogenesis using the isolated perfused rat liver. HFLC diet (79% fat, 19% protein, and 2% carbohydrates in Kcal%) was administered to rats for 4 weeks under three conditions: ad libitum (hypercaloric), isocaloric, and hypocaloric (energy reduction of 20%). Fasting blood glucose levels and total fat in the liver were higher in all HFLC diet rats. Oral glucose tolerance was impaired in isocaloric and hypercaloric groups, although insulin sensitivity was not altered. HFLC diet also caused marked liver metabolic alterations: higher gluconeogenesis rate from lactate and a reduced capacity to metabolize alanine, the latter effect being more intense in the hypocaloric condition. Thus, even when HFLC diets are used for weight loss, our data imply that they can potentially cause harmful consequences for the liver. Key words: alternative diet, hepatic fat, lactate gluconeogenesis, alanine gluconeogenesis, ureagenesis

Childhood trauma (CT) often co-occurs with alcohol use disorder (AUD) and is associated with poor treatment outcome. We could demonstrated that patients with AUD and a history of childhood trauma showed reduced structural connectivity of the amygdala. Here, we additionally aimed to investigate fronto-limbic functional connectivity (FC) in patients with AUD with (AUD-CT) and without (AUD-noCT) CT. Based on findings in CT, we hypothesized reduced FC of the amygdala with the prefrontal cortex in AUD-CT and worse treatment outcome compared to AUD-noCT.Resting state fMRI scans were acquired in abstinent inpatients with AUD and healthy controls (HCs). We compared bilateral amygdala FC between AUD-CT (n = 21), AUD-noCT (n = 22), and HC (n = 27) using seed-based connectivity (SBC) and region-of-interest to region-of-interest (ROI-ROI) analysis. Sociodemographic and alcohol-specific variables (percent days abstinent, PDA) were assessed at treatment admission and three-month follow-up. The Childhood Trauma Questionnaire (CTQ) assessed trauma severity. SBC analysis revealed that AUD-CT showed increased FC of the left and right amygdala with the medial prefrontal cortex and left paracingulate gyrus compared to HC. AUD-CT showed increased ROI-ROI FC of the left with the right amygdala and the right amygdala with the medial prefrontal cortex. Moreover, AUD-CT exhibited a greater reduction of PDA at three-month follow-up compared to AUD-noCT.Increased FC of the amygdala, the medial prefrontal cortex, and paracingulate gyrus in AUD-CT might be a compensatory adaption to the reduced structural connectivity of the amygdala. Those specific alterations of FC in AUD-CT may represent a distinguishable neurobiological subtype of AUD, possibly underlying the complex clinical picture and worse treatment outcome.

Abstract Understanding crystal characteristics down to the atomistic level increasingly emerges as a crucial insight for creating solid state platforms for qubits with reproducible and homogeneous properties. Here, isotope concentration depth profiles in a SiGe/28Si/SiGe heterostructure are analyzed with atom probe tomography (APT) and time‐of‐flight secondary‐ion mass spectrometry down to their respective limits of isotope concentrations and depth resolution. Spin‐echo dephasing times T2echo=128μs and valley energy splittings EVS around 200μeV have been observed for single spin qubits in this quantum well (QW) heterostructure, pointing toward the suppression of qubit decoherence through hyperfine interaction with crystal host nuclear spins or via scattering between valley states. The concentration of nuclear spin‐carrying 29Si is 50 ± 20ppm in the 28Si QW. The resolution limits of APT allow to uncover that both the SiGe/28Si and the 28Si/SiGe interfaces of the QW are shaped by epitaxial growth front segregation signatures on a few monolayer scale. A subsequent thermal treatment, representative of the thermal budget experienced by the heterostructure during qubit device processing, broadens the top SiGe/28Si QW interface by about two monolayers, while the width of the bottom 28Si/SiGe interface remains unchanged. Using a tight‐binding model including SiGe alloy disorder, these experimental results suggest that the combination of the slightly thermally broadened top interface and of a minimal Ge concentration of 0.3% in the QW, resulting from segregation, is instrumental for the observed large EVS=200μeV. Minimal Ge additions

Maria González-Cao,1 Xueting Cai,2 Jilian Wilhelmina Paulina Bracht,3 Xuan Han,2 Yang Yang,2 Carlos Pedraz-Valdunciel,4 Teresa Morán,5 Javier García-Corbacho,6 Andrés Aguilar,1 Reyes Bernabé,7 Pedro De Marchi,8,9 Luciane Sussuchi da Silva,8 Leticia Ferro Leal,8 Rui Manuel Reis,8,10,11 Jordi Codony-Servat,4 Eloisa Jantus-Lewintre,12– 14 Miguel Angel Molina-Vila,4 Peng Cao,2,15 Rafael Rosell1,16 1Translational Cancer Research Unit, Instituto Oncológico Dr Rosell, Dexeus University Hospital, Barcelona, Spain; 2Integrated Traditional Chinese and Western Medicine Department of Affiliated Hospital, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China; 3Amsterdam University Medical Center (UMC), Amsterdam, The Netherlands; 4Laboratory of Oncology, Pangaea Oncology, Quirón Dexeus University Hospital, Barcelona, Spain; 5Medical Oncology Department, Catalan Institute of Oncology (ICO), Germans Trias i Pujol Hospital, Badalona, Spain; 6Medical Oncology Department (Hospital Clinic)/Translational Genomics and Targeted Therapies in Solid Tumors (IDIBAPs), Barcelona, Spain; 7Medical Oncology Department, Hospital Universitario Virgen del Rocío, Sevilla, Spain; 8Molecular Oncology Research Center; Barretos Cancer Hospital, Barretos, Brazil; 9Oncoclinicas, Rio de Janeiro, Brazil; 10Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal; 11ICVS/3b’s – PT Government Associate Laboratory, Braga/Guimarães, Portugal; 12Valencian Community Foundation Principe Felipe Research Center, Laboratory of Molecular Oncology, Valencia, Spain; 13Centro de Investigación Biomédica en Red (CIBERONC), Madrid, Spain; 14Universitat Politècnica de Valencia, Biotechnology Department, Valencia, Spain; 15College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China; 16Laboratory of Molecular Biology, Germans Trias i Pujol Health Sciences Institute and Hospital (IGTP), Badalona, SpainCorrespondence: Rafael Rosell, Laboratory of Molecular Biology, Germans Trias i Pujol Health Sciences Institute and Hospital (IGTP), Camí de les Escoless/n, Badalona, Barcelona, 08916, Spain, Tel +34 930330520, Email rrosell@iconcologia.net Peng Cao, College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, People’s Republic of China, Tel +86 85608666, Email cao_peng@njucm.edu.cnPurpose: High-mobility group box 1 protein (HMGB1) is subject to exportin 1 (XPO1)-dependent nuclear export, and it is involved in functions implicated in resistance to immunotherapy. We investigated whether HMGB1 mRNA expression was associated with response to immune checkpoint inhibitors (ICI) in non-small cell lung cancer (NSCLC).Patients and Methods: RNA was isolated from pretreatment biopsies of patients with advanced NSCLC treated with ICI. Gene expression analysis of several genes, including HMGB1, was conducted using the NanoString Counter analysis system (PanCancer Immune Profiling Panel). Western blotting analysis and cell viability assays in EGFR and KRAS mutant cell lines were carried out. Evaluation of the antitumoral effect of ICI in combination with XPO1 blocker (selinexor) and trametinib was determined in a murine Lewis lung carcinoma model.Results: HMGB1 mRNA levels in NSCLC patients treated with ICI correlated with progression-free survival (PFS) (median PFS 9.0 versus 18.0 months, P=0.008, hazard ratio=0.30 in high versus low HMGB1). After TNF-α stimulation, HMGB1 accumulates in the cytoplasm of PC9 cells, but this accumulation can be prevented by using selinexor or antiretroviral drugs. Erlotinib or osimertinib with selinexor in EGFR-mutant cells and trametinib plus selinexor in KRAS mutant abolish tumor cell proliferation. Selinexor with a PD-1 inhibitor with or without trametinib abrogates the tumor growth in the murine Lewis lung cancer model.Conclusion: An in-depth exploration of the functions of HMGB1 mRNA and protein is expected to uncover new potential targets and provide a basis for treating metastatic NSCLC in combination with ICI.Keywords: HMGB1, immunotherapy, non-small cell lung cancer, Lewis lung cancer murine model, K-Ras mutations

Substantial amounts of organo-pollutants, often persistent and toxic, are generated globally each year, posing a threat to soil, water, groundwater, and air. The pollutants encompass a wide range of substances from various sources, which include solid as well as liquid ones, such as landfill leachates and wastewaters. The compounds include paper and pulp mill byproducts, pharmaceuticals, diverse types of plastics, hydrocarbons, pigments, and dyes, as well as pesticides and insecticides. Fungal bioremediation stands out as a promising technology that uses the metabolic potential of fungi to eliminate or mitigate the impact of pollutants. Notably, species of the genus Pycnoporus exhibit significant capabilities for degrading a broad spectrum of toxic molecules. This degradation is facilitated by released ligninolytic enzymes, especially laccase, and cellular enzymes pertaining to the cytochrome P450 monooxygenase system. The laccase, which is overproduced by the genus Pycnoporus, is quite remarkable for its high redox potential. The objective of this review is to highlight the proficiency of the Pycnoporus genus in the degradation of pollutants in submerged and solid-state fermentation. Recent studies conducted over the past decade consistently highlight the Pycnoporus genus as a robust contender in the realm of white biotechnology.

Background: Numerous studies show that electroconvulsive therapy (ECT) induces hippocampal neuroplasticity, but findings are inconsistent regarding its clinical relevance. This study aims to investigate ECT-induced plasticity of anterior and posterior hippocampi using mathematical complexity measures in neuroimaging, namely Higuchi's fractal dimension (HFD) for fMRI time series and the fractal dimension of cortical morphology (FD-CM). Furthermore, we explore the potential of these complexity measures to predict ECT treatment response. Methods: Twenty patients with a current depressive episode (16 with major depressive disorder and 4 with bipolar disorder) underwent MRI-scans before and after an ECT-series. Twenty healthy controls matched for age and sex were also scanned twice for comparison purposes. Resting-state fMRI data were processed, and HFD was computed for anterior and posterior hippocampi. Group-by-time effects for HFD in anterior and posterior hippocampi were calculated and correlations between HFD changes and improvement in depression severity were examined. For FD-CM analyses, we preprocessed structural MRI with CAT12′s surface-based methods. We explored group-by-time effects for FD-CM and the predictive value of baseline HFD and FD-CM for treatment outcome. Results: Patients exhibited a significant increase in bilateral hippocampal HFD from baseline to follow-up scans. Right anterior hippocampal HFD increase was associated with reductions in depression severity. We found no group differences and group-by-time effects in FD-CM. After applying a whole-brain regression analysis, we found that baseline FD-CM in the left temporal pole predicted reduction of overall depression severity after ECT. Baseline hippocampal HFD did not predict treatment outcome. Conclusion: This study suggests that HFD and FD-CM are promising imaging markers to investigate ECT-induced neuroplasticity associated with treatment response.

BACKGROUND AND OBJECTIVES: The red flags screening purpose is to ensure that signs and symptoms that raise suspicion of serious diseases are being considered during the assessment, assisting physical therapists in their clinical decision process. Brazilian physical therapists are autonomous and can act as first contact professionals in the management of musculoskeletal disorders, therefore, they need to know how to recognize, screen and refer patients with red flags for better therapeutic management. The objectives of this study were to verify whether Brazilian physical therapists can recognize and manage patients who presented red flags, compare professionals’ skills regarding different academic degree levels and clinical experience and identify which factors can influence the results. METHODS: A cross-sectional and quantitative research was conducted, collected from an online questionnaire. The target audience consisted of Brazilian physical therapists who have clinical experience in the management of patients with musculoskeletal disorders. Participants filled demographic data and made clinical decisions based on six clinical cases created by the authors, based on the literature, and reviewed by three experts. Data were analyzed using descriptive statistics, the Chi-square test of independence and logistic regression. RESULTS: The study analyzed 384 answers from Brazilian physical therapists with clinical experience in musculoskeletal conditions. Brazilian physical therapists, in general, have not shown to be able to properly recognize and manage the clinical cases involving red flags, with 23.2% of the sample performing appropriate management for medical conditions, 53.9% for emergency conditions and 61.8% for medical conditions with associated musculoskeletal dysfunction. More years of clinical experience and post-professional education did not positively influence the outcomes. Higher academic degrees (Doctorate) can influence positively on the management of non-emergency medical conditions. CONCLUSION: Brazilian physical therapists who work with patients with musculoskeletal disorders perform poorly in identifying red flags in hypothetical clinical cases.

Individuals with severe academic challenges constitute one of the most vulnerable groups of our society. Science has to find ways to help arm them against life's challenges and cope with the many risk factors that they are usually confronted with. Team sports like baseball seem to be a suitable means of achieving that goal. In this qualitative study, we interviewed a young man with learning disabilities who played professional baseball for two years. Our participant talked about his life as a student and related how his career in baseball made his academic difficulties appear much less significant. He gave some meaningful insights into what helped him to build a happy and fulfilling life for himself -- not only in spite of his challenges but also because of what his learning disabilities taught him. Support from significant others, a sense of purpose, a fighting spirit ignited by sports, and the success that he experienced on the baseball field were among the most relevant factors. Overall, this study highlights the importance of finding an outlet for young people with learning disabilities where their academic problems fade into the background while their talents are validated.

Self-diffusion in amorphous germanium is studied at temperatures between 325 and 370 °C utilizing amorphous isotopically controlled germanium multilayer structures. The isotope multilayer is epitaxially grown on a single crystalline germanium-on-insulator structure by means of molecular beam epitaxy and subsequently amorphized by self-ion implantation. After heat treatment, the diffusional broadening of the isotope structure is measured with time-of-flight secondary ion mass spectrometry. The temperature dependence of self-diffusion is accurately described by the Arrhenius equation with the activation enthalpy Q = (2.21 ± 0.12) eV and pre-exponential factor D0=(2.32−2.10+20.79) cm2 s−1. The activation enthalpy equals the activation enthalpy of solid phase epitaxial recrystallization (SPER). This agreement suggests that self-diffusion in amorphous germanium is similar to SPER, also mainly mediated by local bond rearrangements. Classical molecular dynamics simulations with a modified Stillinger–Weber-type interatomic potential yield results that are consistent with the experimental data and support the proposed atomic mechanism.

BackgroundIncreasing pressure on limited intensive care capacities often requires a subjective assessment of a patient's discharge readiness in the absence of established Admission, Discharge, and Transfer (ADT) guidelines. To avoid suboptimal care transitions, it is important to define clear guidelines for the admission and discharge of intensive care patients and to optimize transfer processes between the intensive care unit (ICU) and lower care levels. To achieve these goals, structured insights into usual ICU discharge and transfer practices are essential. This study aimed to generate these insights by focusing on involved stakeholders, established processes, discharge criteria and tools, relevant performance metrics, and current barriers to a timely and safe discharge.MethodIn 2022, a structured, web-based, anonymous cross-sectional survey was conducted, aimed at practicing ICU physicians, nurses, and bed coordinators. The survey consisted of 29 questions (open, closed, multiple choice, and scales) that were divided into thematic blocks. The study was supported by several national and international societies for intensive care medicine and nursing.ResultsA total of 219 participants from 40 countries (105 from Germany) participated in the survey. An overload of acute care resources with ~90% capacity utilization in the ICU and the general ward (GW) leads to not only premature but also delayed patient transfers due to a lack of available ward and intermediate care (IMC) beds. After multidisciplinary rounds within the intensive care team, the ICU clinician on duty usually makes the final transfer decision, while one-third of the panel coordinates discharge decisions across departmental boundaries. By the end of the COVID-19 pandemic, half of the hospitals had implemented ADT policies. Among these hospitals, nearly one-third of the hospitals had specific transfer criteria established, consisting primarily of vital signs and laboratory data, patient status and autonomy, and organization-specific criteria. Liaison nurses were less common but were ranked right after the required IMC capacities to bridge the care gap between the ICU and normal wards. In this study, 80% of the participants suggested that transfer planning would be easier if there was good transparency regarding the capacity utilization of lower care levels, a standardized transfer process, and improved interdisciplinary communication.ConclusionTo improve care transitions, transfer processes should be managed proactively across departments, and efforts should be made to identify and address care gaps.

BackgroundSepsis, a life-threatening condition caused by the dysregulated host response to infection, is a major global health concern. Understanding the impact of viral or bacterial pathogens in sepsis is crucial for improving patient outcomes. This study aimed to investigate the human cytomegalovirus (HCMV) seropositivity as a risk factor for development of sepsis in patients with COVID-19.MethodsA multicenter observational study enrolled 95 intensive care patients with COVID-19-induced sepsis and 80 post-surgery individuals as controls. HCMV serostatus was determined using an ELISA test. Comprehensive clinical data, including demographics, comorbidities, and 30-day mortality, were collected. Statistical analyses evaluated the association between HCMV seropositivity and COVID-19 induced sepsis.ResultsThe prevalence of HCMV seropositivity did not significantly differ between COVID-19-induced sepsis patients (78%) and controls (71%, p = 0.382) in the entire cohort. However, among patients aged ≤60 years, HCMV seropositivity was significantly higher in COVID-19 sepsis patients compared to controls (86% vs 61%, respectively; p = 0.030). Nevertheless, HCMV serostatus did not affect 30-day survival.DiscussionThese findings confirm the association between HCMV seropositivity and COVID-19 sepsis in non-geriatric patients. However, the lack of an independent effect on 30-day survival can be explained by the cross-reactivity of HCMV specific CD8+ T-cells towards SARS-CoV-2 peptides, which might confer some protection to HCMV seropositive patients. The inclusion of a post-surgery control group strengthens the generalizability of the findings. Further research is needed to elucidate the underlying mechanisms of this association, explore different patient populations, and identify interventions for optimizing patient management.ConclusionThis study validates the association between HCMV seropositivity and severe COVID-19-induced sepsis in non-geriatric patients, contributing to the growing body of evidence on viral pathogens in sepsis. Although HCMV serostatus did not independently influence 30-day survival, future investigations should focus on unraveling the intricate interplay between HCMV, immune responses, and COVID-19. These insights will aid in risk stratification and the development of targeted interventions for viral sepsis.