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Abstract Advances in artificial intelligence have cultivated a strong interest in developing and validating the clinical utilities of computer-aided diagnostic models. Machine learning for diagnostic neuroimaging has often been applied to detect psychological and neurological disorders, typically on small-scale datasets or data collected in a research setting. With the collection and collation of an ever-growing number of public datasets that researchers can freely access, much work has been done in adapting machine learning models to classify these neuroimages by diseases such as Alzheimer’s, ADHD, autism, bipolar disorder, and so on. These studies often come with the promise of being implemented clinically, but despite intense interest in this topic in the laboratory, limited progress has been made in clinical implementation. In this review, we analyze challenges specific to the clinical implementation of diagnostic AI models for neuroimaging data, looking at the differences between laboratory and clinical settings, the inherent limitations of diagnostic AI, and the different incentives and skill sets between research institutions, technology companies, and hospitals. These complexities need to be recognized in the translation of diagnostic AI for neuroimaging from the laboratory to the clinic.

Abstract Background In recent years, neuroimaging with deep learning (DL) algorithms have made remarkable advances in the diagnosis of neurodegenerative disorders. However, applying DL in different medical domains is usually challenged by lack of labeled data. To address this challenge, transfer learning (TL) has been applied to use state-of-the-art convolution neural networks pre-trained on natural images. Yet, there are differences in characteristics between medical and natural images, also image classification and targeted medical diagnosis tasks. The purpose of this study is to investigate the performance of specialized and TL in the classification of neurodegenerative disorders using 3D volumes of 18F-FDG-PET brain scans. Results Results show that TL models are suboptimal for classification of neurodegenerative disorders, especially when the objective is to separate more than two disorders. Additionally, specialized CNN model provides better interpretations of predicted diagnosis. Conclusions TL can indeed lead to superior performance on binary classification in timely and data efficient manner, yet for detecting more than a single disorder, TL models do not perform well. Additionally, custom 3D model performs comparably to TL models for binary classification, and interestingly perform better for diagnosis of multiple disorders. The results confirm the superiority of the custom 3D-CNN in providing better explainable model compared to TL adopted ones.

Background: Neurotransmitters deficits in Frontotemporal Dementia (FTD) are still poorly understood. Better knowledge of neurotransmitters impairment, especially in prodromal disease stages, might tailor symptomatic treatment approaches. Methods: In the present study, we applied JuSpace toolbox, which allowed for cross-modal correlation of Magnetic Resonance Imaging (MRI)-based measures with nuclear imaging derived estimates covering various neurotransmitter systems including dopaminergic, serotonergic, noradrenergic, GABAergic and glutamatergic neurotransmission.We included 392 mutation carriers (157 GRN, 164 C9orf72, 71 MAPT), together with 276 non-carrier cognitively healthy controls (HC). We tested if the spatial patterns of grey matter volume (GMV) alterations in mutation carriers (relative to HC) are correlated with specific neurotransmitter systems in prodromal (CDR® plus NACC FTLD = 0.5) and in symptomatic (CDR® plus NACC FTLD≥1) FTD. Results: In prodromal stages of C9orf72 disease, voxel-based brain changes were significantly associated with spatial distribution of dopamine and acetylcholine pathways; in prodromal MAPT disease with dopamine and serotonin pathways, while in prodromal GRN disease no significant findings were reported (p

AbstractRecent mechanistic models argue for a key role of rhythm processing in both speech production and speech perception. Patients with the non-fluent variant (NFV) of primary progressive aphasia (PPA) with apraxia of speech (AOS) represent a specific study population in which this link can be examined. Previously, we observed impaired rhythm processing in NFV with AOS. We hypothesized that a shared neurocomputational mechanism structures auditory input (sound and speech) and output (speech production) in time, a “temporal scaffolding” mechanism. Since considerable white matter damage is observed in NFV, we test here whether white matter changes are related to impaired rhythm processing. Forty-seven participants performed a psychoacoustic test battery: 12 patients with NFV and AOS, 11 patients with the semantic variant of PPA, and 24 cognitively intact age- and education-matched controls. Deformation-based morphometry was used to test whether white matter volume correlated to rhythmic abilities. In 34 participants, we also obtained tract-based metrics of the left Aslant tract, which is typically damaged in patients with NFV. Nine out of 12 patients with NFV displayed impaired rhythmic processing. Left frontal white matter atrophy adjacent to the supplementary motor area (SMA) correlated with poorer rhythmic abilities. The structural integrity of the left Aslant tract also correlated with rhythmic abilities. A colocalized and perhaps shared white matter substrate adjacent to the SMA is associated with impaired rhythmic processing and motor speech impairment. Our results support the existence of a temporal scaffolding mechanism structuring perceptual input and speech output.

Abstract Background Blood-based amyloid biomarkers may provide a non-invasive, cost-effective and scalable manner for detecting cerebral amyloidosis in early disease stages. Methods In this prospective cross-sectional study, we quantified plasma Aβ1–42/Aβ1–40 ratios with both routinely available ELISAs and novel SIMOA Amyblood assays, and provided a head-to-head comparison of their performances to detect cerebral amyloidosis in a nondemented elderly cohort (n = 199). Participants were stratified according to amyloid-PET status, and the performance of plasma Aβ1–42/Aβ1–40 to detect cerebral amyloidosis was assessed using receiver operating characteristic analysis. We additionally investigated the correlations of plasma Aβ ratios with amyloid-PET and CSF Alzheimer’s disease biomarkers, as well as platform agreement using Passing-Bablok regression and Bland-Altman analysis for both Aβ isoforms. Results ELISA and SIMOA plasma Aβ1–42/Aβ1–40 detected cerebral amyloidosis with identical accuracy (ELISA: area under curve (AUC) 0.78, 95% CI 0.72–0.84; SIMOA: AUC 0.79, 95% CI 0.73–0.85), and both increased the performance of a basic demographic model including only age and APOE-ε4 genotype (p ≤ 0.02). ELISA and SIMOA had positive predictive values of respectively 41% and 36% in cognitively normal elderly and negative predictive values all exceeding 88%. Plasma Aβ1–42/Aβ1–40 correlated similarly with amyloid-PET for both platforms (Spearman ρ = − 0.32, p

Abstract Introduction The eye offers potential for the diagnosis of Alzheimer’s disease (AD) with retinal imaging techniques being explored to quantify amyloid accumulation and aspects of neurodegeneration. To assess these changes, this proof-of-concept study combined hyperspectral imaging and optical coherence tomography to build a classification model to differentiate between AD patients and controls. Methods In a memory clinic setting, patients with a diagnosis of clinically probable AD (n = 10) or biomarker-proven AD (n = 7) and controls (n = 22) underwent non-invasive retinal imaging with an easy-to-use hyperspectral snapshot camera that collects information from 16 spectral bands (460–620 nm, 10-nm bandwidth) in one capture. The individuals were also imaged using optical coherence tomography for assessing retinal nerve fiber layer thickness (RNFL). Dedicated image preprocessing analysis was followed by machine learning to discriminate between both groups. Results Hyperspectral data and retinal nerve fiber layer thickness data were used in a linear discriminant classification model to discriminate between AD patients and controls. Nested leave-one-out cross-validation resulted in a fair accuracy, providing an area under the receiver operating characteristic curve of 0.74 (95% confidence interval [0.60–0.89]). Inner loop results showed that the inclusion of the RNFL features resulted in an improvement of the area under the receiver operating characteristic curve: for the most informative region assessed, the average area under the receiver operating characteristic curve was 0.70 (95% confidence interval [0.55, 0.86]) and 0.79 (95% confidence interval [0.65, 0.93]), respectively. The robust statistics used in this study reduces the risk of overfitting and partly compensates for the limited sample size. Conclusions This study in a memory-clinic-based cohort supports the potential of hyperspectral imaging and suggests an added value of combining retinal imaging modalities. Standardization and longitudinal data on fully amyloid-phenotyped cohorts are required to elucidate the relationship between retinal structure and cognitive function and to evaluate the robustness of the classification model.

The CoronaVac vaccine is the most used anti-SARS-CoV-2 vaccine worldwide. Previous data indicate that this vaccine produces a lower immune response than RNA vaccines such as BNT162b2. End-stage renal disease (ESRD) patients have an increased rate of COVID-19 and a reduced immune response to vaccinations. Currently, there is little data on this population’s immune response induced by CoronaVac. Methods: This study involved a prospective cohort of ESRD patients in chronic hemodialysis who received a two-dose immunization scheme of either CoronaVac (Sinovac Biotech) or BNT162b2 vaccines (Pfizer-BioNTech). We measured the plasma levels of anti-SARS-CoV-2 IgG antibodies. We determined antibody titers before immunization, 2 and 4 months after two doses, plus 4 months after a booster dose. Results: We evaluated 208 patients in three hemodialysis centers. The mean age was 62.6 ± 15.6 years, of whom 91 were female (41.75%). Eighty-one patients (38.94%) received the BNT162b2 vaccine and 127 (61.06%) received the CoronaVac vaccine. Patients who received the BNT162b2 vaccine had a higher humoral response compared to those who received the CoronaVac vaccine (4 months after the second dose: BNT162b2: 88.89%, CoronaVac: 51.97%, p < 0.001; 4 months after the booster: BNT162b2: 98.77%, CoronaVac: 86.61%, p < 0.001). Conclusions: Our results suggest that the CoronaVac vaccine induced a lower humoral response than the BNT162b2 vaccine in ESRD patients on hemodialysis.

Mutations in the granulin gene (GRN) cause familial frontotemporal dementia. Understanding the structural brain changes in presymptomatic GRN carriers would enforce the use of neuroimaging biomarkers for early diagnosis and monitoring. We studied 100 presymptomatic GRN mutation carriers and 94 noncarriers from the Genetic Frontotemporal dementia initiative (GENFI), with MRI structural images. We analyzed 3T MRI structural images using the FreeSurfer pipeline to calculate the whole brain cortical thickness (CTh) for each subject. We also perform a vertex-wise general linear model to assess differences between groups in the relationship between CTh and diverse covariables as gender, age, the estimated years to onset and education. We also explored differences according to TMEM106B genotype, a possible disease modifier. Whole brain CTh did not differ between carriers and noncarriers. Both groups showed age-related cortical thinning. The group-by-age interaction analysis showed that this age-related cortical thinning was significantly greater in GRN carriers in the left superior frontal cortex. TMEM106B did not significantly influence the age-related cortical thinning. Our results validate and expand previous findings suggesting an increased CTh loss associated with age and estimated proximity to symptoms onset in GRN carriers, even before the disease onset.

Background: Studies have previously shown evidence for presymptomatic cortical atrophy in genetic FTD. Whilst initial investigations have also identified early deep grey matter volume loss, little is known about the extent of subcortical involvement, particularly within subregions, and how this differs between genetic groups. Methods: 480 mutation carriers from the Genetic FTD Initiative (GENFI) were included (198 GRN, 202 C9orf72, 80 MAPT), together with 298 non-carrier cognitively normal controls. Cortical and subcortical volumes of interest were generated using automated parcellation methods on volumetric 3 T T1-weighted MRI scans. Mutation carriers were divided into three disease stages based on their global CDR® plus NACC FTLD score: asymptomatic (0), possibly or mildly symptomatic (0.5) and fully symptomatic (1 or more). Results: In all three groups, subcortical involvement was seen at the CDR 0.5 stage prior to phenoconversion, whereas in the C9orf72 and MAPT mutation carriers there was also involvement at the CDR 0 stage. In the C9orf72 expansion carriers the earliest volume changes were in thalamic subnuclei (particularly pulvinar and lateral geniculate, 9–10%) cerebellum (lobules VIIa-Crus II and VIIIb, 2–3%), hippocampus (particularly presubiculum and CA1, 2–3%), amygdala (all subregions, 2–6%) and hypothalamus (superior tuberal region, 1%). In MAPT mutation carriers changes were seen at CDR 0 in the hippocampus (subiculum, presubiculum and tail, 3–4%) and amygdala (accessory basal and superficial nuclei, 2–4%). GRN mutation carriers showed subcortical differences at CDR 0.5 in the presubiculum of the hippocampus (8%). Conclusions: C9orf72 expansion carriers show the earliest and most widespread changes including the thalamus, basal ganglia and medial temporal lobe. By investigating individual subregions, changes can also be seen at CDR 0 in MAPT mutation carriers within the limbic system. Our results suggest that subcortical brain volumes may be used as markers of neurodegeneration even prior to the onset of prodromal symptoms.

The examination of semantic cognition has traditionally identified word concreteness as well as valence as two of the principal dimensions in the representation of conceptual knowledge. More recently, corpus-based vector space models as well as graph-theoretical analysis of large-scale task-related behavioural responses have revolutionized our insight into how the meaning of words is structured. In this fMRI study, we apply representational similarity analysis to investigate the conceptual representation of abstract words. Brain activity patterns were related to a cued-association based graph as well as to a vector-based co-occurrence model of word meaning. Twenty-six subjects (19 females and 7 males) performed an overt repetition task during fMRI. First, we performed a searchlight classification procedure to identify regions where activity is discriminable between abstract and concrete words. These regions were left inferior frontal gyrus, the upper and lower bank of the superior temporal sulcus bilaterally, posterior middle temporal gyrus and left fusiform gyrus. Representational Similarity Analysis demonstrated that for abstract words, the similarity of activity patterns in the cortex surrounding the superior temporal sulcus bilaterally and in the left anterior superior temporal gyrus reflects the similarity in word meaning. These effects were strongest for semantic similarity derived from the cued association-based graph and for affective similarity derived from either of the two models. The latter effect was mainly driven by positive valence words. This research highlights the close neurobiological link between the information structure of abstract and affective word content and the similarity in activity pattern in the lateral and anterior temporal language system.

Abstract Background A subset of patients with the nonfluent variant of primary progressive aphasia (PPA) exhibit concomitant single-word comprehension problems, constituting a ‘mixed variant’ phenotype. This phenotype is rare and currently not fully characterized. The aim of this study was twofold: to assess the prevalence and nature of single-word comprehension problems in the nonfluent variant and to study multimodal imaging characteristics of atrophy, tau, and amyloid burden associated with this mixed phenotype. Methods A consecutive memory-clinic recruited series of 20 PPA patients (12 nonfluent, five semantic, and three logopenic variants) were studied on neurolinguistic and neuropsychological domains relative to 64 cognitively intact healthy older control subjects. The neuroimaging battery included high-resolution volumetric magnetic resonance imaging processed with voxel-based morphometry, and positron emission tomography with the tau-tracer [18F]-THK5351 and amyloid-tracer [11C]-Pittsburgh Compound B. Results Seven out of 12 subjects who had been classified a priori with nonfluent variant PPA showed deficits on conventional single-word comprehension tasks along with speech apraxia and agrammatism, corresponding to a mixed variant phenotype. These mixed variant cases included three females and four males, with a mean age at onset of 65 years (range 44–77 years). Object knowledge and object recognition were additionally affected, although less severely compared with the semantic variant. The mixed variant was characterized by a distributed atrophy pattern in frontal and temporoparietal regions. A more focal pattern of elevated [18F]-THK5351 binding was present in the supplementary motor area, the left premotor cortex, midbrain, and basal ganglia. This pattern was closely similar to that seen in pure nonfluent variant PPA. At the individual patient level, elevated [18F]-THK5351 binding in the supplementary motor area and premotor cortex was present in six out of seven mixed variant cases and in five and four of these cases, respectively, in the thalamus and midbrain. Amyloid biomarker positivity was present in two out of seven mixed variant cases, compared with none of the five pure nonfluent cases. Conclusions A substantial proportion of PPA patients with speech apraxia and agrammatism also have single-word comprehension deficits. At the neurobiological level, the mixed variant shows a high degree of similarity with the pure nonfluent variant of PPA. Trial registration EudraCT, 2014–002976-10. Registered on 13-01-2015.

Abstract Background Biomarkers such as amyloid imaging are increasingly used for diagnosis in the early stages of Alzheimer’s disease. Very few studies have examined this from the perspective of the patient. To date, there is only limited evidence about how patients experience and value disclosure in an early disease stage. Methods Semistructured interviews were carried out with 38 patients with amnestic mild cognitive impairment as part of an investigator-driven diagnostic trial (EudraCT, 2013-004671-12; registered on 20 June 2014) in which participants could opt to know the binary outcome (positive/negative) result of their amyloid positron emission tomography (PET) scan. Verbatim transcripts of the interviews were evaluated using qualitative content analysis and NVivo 11 software. Results Eight of 38 patients received a positive amyloid PET scan result, and the remaining 30 patients received a negative amyloid PET scan result. After disclosure of the result to the patients, we interviewed each patient twice: 2 weeks after disclosure and 6 months after disclosure. Patients had difficulties in repeating the exact words used during disclosure of their amyloid PET scan result by the neurologist; yet, they could recall the core message of the result in their own words. Some patients were confused by the terminology of an amyloid-positive/negative test result. At 6 months, two of eight patients with a positive amyloid PET scan result experienced emotional difficulties (sadness, feeling worried). Three of 30 patients with a negative amyloid PET scan result started to doubt whether they had received the correct result. Patients reported that they experienced advantages after the disclosure, such as information about their health status, the possibility of making practical arrangements, medication, enjoying life more, and a positive impact on relationships. They also reported disadvantages following disclosure, such as having emotional difficulties, feeling worried about when their symptoms might worsen, the risk of a more patronizing attitude by relatives, and the possibility of a wrong diagnosis. Conclusions This exploratory study shows that the majority of patients can accurately recall the information received during disclosure. The experienced advantages and disadvantages reported by our patients depended on the outcome of the result (positive or negative) and the interval of the conducted interview (2 weeks or 6 months after amyloid PET disclosure). Discrepancies were found between patients’ expectations according to the interview prior to amyloid PET disclosure (Vanderschaeghe et al. [Neuroethics. 2017;10:281–97]) and their actual experiences after their amyloid PET disclosure.

Primary progressive aphasia (PPA) is a heterogeneous syndrome with various neuropathological causes for which no medical treatment with proven efficacy exists. Basal forebrain (BF) volume loss has been reported in PPA but its relation to cholinergic depletion is still unclear. The primary objective of this study was to investigate whether cholinergic alterations occur in PPA variants and how this relates to BF volume loss. An academic memory clinic based consecutive series of 11 PPA patients (five with the semantic variant (SV), four with the logopenic variant (LV) and two with the nonfluent variant (NFV)) participated in this cross-sectional in vivo PET imaging study together with 10 healthy control subjects. Acetylcholinesterase (AChE) activity was quantitatively measured in the neo- and allocortex using N-[11C]-Methylpiperidin-4-yl propionate (PMP)-PET with arterial sampling and metabolite correction. Whole brain and BF volumes were quantified using voxel-based morphometry on high-resolution magnetic resonance imaging (MRI) scans. In the PPA group, only LV cases showed decreases in AChE activity levels compared to controls. Surprisingly, a substantial number of SV cases showed significant AChE activity increases compared to controls. BF volume did not correlate with AChE activity levels in PPA. To conclude, in our sample of PPA patients, LV but not SV was associated with cholinergic depletion. BF atrophy in PPA does not imply cholinergic depletion.

Simulations have been carried out for a multi-body launch vehicle configuration using CFD code 'PARAS-3D'. PARAS-3D is a Reynolds Averaged Navier Stokes equations (RANS) solver with k-ε turbulence model. The transonic regime is a critical regime for any launch vehicle configuration because of its typical aerodynamic characteristics such as shock wave disturbances. CFD flow simulations are done at zero degree angle of attack for various strap-on nose cone angle, nose radius and Mach numbers 0.8, 0.9, 0.95, 1.05. For different positions of strap-on obtained through forward and backward shift from its original position, the influence of strap-on on fore body of the core of launch vehicle is investigated. In this article, the results pertaining to the pressure distribution and Mach contour over launch vehicle configuration is presented.

Amyotrophic lateral sclerosis (ALS) has long been considered to be a purely motor disorder. However, it has become apparent that many ALS patients develop cognitive and behavioral manifestations similar to frontotemporal dementia and the term amyotrophic lateral sclerosis-frontotemporal spectrum disorder (ALS-FTSD) is now used in these circumstances. This review is intended to be an overview of the cognitive and behavioral manifestations commonly encountered in ALS patients with the goal of improving case-oriented management in clinical practice. We introduce the principal ALS-FTSD subtypes and comment on their principal clinical manifestations, neuroimaging findings, neuropathological and genetic background, and summarize available therapeutic options. Diagnostic criteria for ALS-FTSD create distinct categories based on the type of neuropsychological manifestations, i.e., changes in behavior, impaired social cognition, executive dysfunction, and language or memory impairment. Cognitive impairment is found in up to 65%, while frank dementia affects about 15% of ALS patients. ALS motor and cognitive manifestations can worsen in parallel, becoming more pronounced when bulbar functions (affecting speech, swallowing, and salivation) are involved. Dementia can precede or develop after the appearance of motor symptoms. ALS-FTSD patients have a worse prognosis and shorter survival rates than patients with ALS or frontotemporal dementia alone. Important negative prognostic factors are behavioral and personality changes. From the clinician’s perspective, there are five major distinguishable ALS-FTSD subtypes: ALS with cognitive impairment, ALS with behavioral impairment, ALS with combined cognitive and behavioral impairment, fully developed frontotemporal dementia in combination with ALS, and comorbid ALS and Alzheimer’s disease. Although the most consistent ALS and ALS-FTSD pathology is a disturbance in transactive response DNA binding protein 43 kDa (TDP-43) metabolism, alterations in microtubule-associated tau protein metabolism have also been observed in ALS-FTSD. Early detection and careful monitoring of cognitive deficits in ALS are crucial for patient and caregiver support and enable personalized management of individual patient needs.

According to a recent study, semantic similarity between concrete entities correlates with the similarity of activity patterns in left middle IPS during category naming. We examined the replicability of this effect under passive viewing conditions, the potential role of visuoperceptual similarity, where the effect is situated compared to regions that have been previously implicated in visuospatial attention, and how it compares to effects of object identity and location. Forty-six subjects participated. Subjects passively viewed pictures from two categories, musical instruments and vehicles. Semantic similarity between entities was estimated based on a concept-feature matrix obtained in more than 1,000 subjects. Visuoperceptual similarity was modeled based on the HMAX model, the AlexNet deep convolutional learning model, and thirdly, based on subjective visuoperceptual similarity ratings. Among the IPS regions examined, only left middle IPS showed a semantic similarity effect. The effect was significant in hIP1, hIP2, and hIP3. Visuoperceptual similarity did not correlate with similarity of activity patterns in left middle IPS. The semantic similarity effect in left middle IPS was significantly stronger than in the right middle IPS and also stronger than in the left or right posterior IPS. The semantic similarity effect was similar to that seen in the angular gyrus. Object identity effects were much more widespread across nearly all parietal areas examined. Location effects were relatively specific for posterior IPS and area 7 bilaterally. To conclude, the current findings replicate the semantic similarity effect in left middle IPS under passive viewing conditions, and demonstrate its anatomical specificity within a cytoarchitectonic reference frame. We propose that the semantic similarity effect in left middle IPS reflects the transient uploading of semantic representations in working memory.

Trata-se de uma pesquisa descritiva quantitativa que teve o seguinte objetivo: identificar as taxas de infecção hospitalar relacionadas ao trato vascular em recém-nascidos hospitalizados na Unidade de Terapia Intensiva Neonatal de um Hospital Universitário localizado no estado do Rio de Janeiro no período de 2005 a 2007. A amostra foi constituída todos os recém-nascidos internados em 2005 e 2007. Os resultados indicaram que, embora a taxa de infecções hospitalares em 2007 seja menor que no ano de 2005, a proporção de infecções relacionadas ao trato vascular sofreu um discreto aumento considerando as demais topografias. Embora a educação continuada seja empregada na unidade, acredita-se que fatores como a alta rotatividade de profissionais e o uso de mais cateteres venosos centrais na rotina reduzam sua efetividade. Desta forma, foram elaboradas algumas propostas para a redução das infecções hospitalares na unidade estudada.

The study of research proposes a systematic pattern for optimization and fabrication of a sustainable-cost effective electrochemical sensor made by Bi-CdFe 2 O 4 (BCDF) nanoparticle and graphite powder. The structural examinations of synthesized BCDF materials were analyzed by specific spectral techniques viz.; P-XRD, SEM-EDX, TEM, XPS, FT-IR and DRS techniques. The modified sensor electrode offer a significant electrochemical properties that can improve the material selectivity and sensitivity actions measured by Cyclic Voltammetric (CV) and Electrochemical Impedance Spectral (EIS) plots. We demonstrated a developed highly-purity BCDF-graphite paste electrode for sensing actions on Paracetamol and Lead (Pb 2+ ) ions under 0.1 M KCl. The excellent sensing activity towards Lead ions and Paracetamol confirmed by its redox potential peaks at scan rate of 1-5 V/s with maximum sensitivity of -0.61 V and 0.69 V respectively. The excellent photo-dye-degradation action of BCDF (98.2%) than those of host CDF (81.6%) on Rose Bengal (RB) dye was demonstrated. Its kinetic study reveals that this process follows first order kinetics and rate constants of the host (18.1 × 10 -3 min -1 ) and BCDF (39.2 × 10 -3 min -1 ) were measured. Thus, the synthesized BCDF electrode provides a new perception for developing specific nano-sensor towards detection of toxic metals., (© 2024. The Author(s).)

Background: QbTest is a commercially available, computerised test of attention, impulsivity, and activity designed to assist with the diagnosis of attention deficit hyperactivity disorder (ADHD). Health Innovation East Midlands (formerly East Midlands AHSN), led the implementation of the QbTest on behalf of the 15 Health Innovation Networks across Child and Adolescent Mental Health services (CAMHS) and Paediatric sites in England between April 2020 and March 2023. We evaluate the impact of this programme on diagnostic assessment at participating sites., Methods: A mixed-methods approach was used including: case-note data collected on 10-30 cases per site pre and post QbTest implementation; interviews with healthcare staff working with QbTest; and surveys to explore perspectives of healthcare staff and patients/carers. Case-note data was descriptively analysed to compare time to diagnosis (number of appointments and days) pre/post QbTest implementation. Survey data was analysed descriptively. Qualitative interview data was explored using thematic analysis., Results: Case-note data was provided by 20 sites across England. Comparison of mean values pre- and post-QbTest implementation identified a decrease of 0.37 (11.5%) in number of appointments to reach a diagnostic decision, a 55-day (12.5%) increase in days from initial referral to diagnosis, and a 12-day (10.3%) increase in days to reach a diagnostic decision. Exploratory analyses indicated greater benefit for Paediatric services over CAMHS, in terms of a decrease in days from referral to diagnosis and number of appointments to diagnosis. Interviews with healthcare staff (n=21) revealed that the QbTest was perceived to support a faster, more efficient diagnostic process. Survey data (n=65 healthcare staff, n=22 patients/carers) identified that the QbTest helped patients understand their symptoms and the diagnostic decision.  Although some logistical issues (e.g., room requirements) and patient issues (e.g., sensory sensitivity) were identified, healthcare staff considered that QbTest was easily incorporated into the ADHD assessment pathway., Conclusion: The national implementation of QbTest in ADHD clinics resulted in a small reduction in the number of clinical appointments needed to reach a diagnostic decision, with greatest benefit demonstrated in Paediatric sites. Data were impacted by COVID-19 therefore, further evaluation is warranted., (© 2024. The Author(s).)

This conceptual review explores the full potential of mentoring for diversity initiatives. Using a positive relationships lens, I describe how focusing on average relationships obscures the benefits of high-quality mentoring and how traditional views of mentoring as hierarchical, one-way relationships limit our understanding of its role in advancing social justice. Addressing these limitations, I extend relational mentoring and diversified mentoring theories to introduce the Triple A Model of Social Justice Mentoring. This model holds that the effects of high-quality mentoring extend beyond the relationship to influence social justice outcomes. Both members can learn about diversity and experience relational dynamics that foster allyship, agentic empowerment and authentic identities. Implications for formal mentoring, diverse friendships, mentoring episodes and high-quality connections are discussed., Competing Interests: Declaration of competing interest The author declares no conflict of interest., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Therapeutic clinical relationships and skilled communication are foundational elements of high-quality hospice and palliative care. Both require that we draw on the most valuable, yet limited, resource in our practice: clinician time. As the demand for serious illness care continues to outpace the supply of trained palliative care clinicians, we must consider time-efficiency as a key component of clinical effectiveness. Equally, many skilled interventions, including serious illness communication, can occur during time-efficient encounters, which still preserve compassion and authentic presence. This report invites clinicians to reevaluate the meaning and use of time in modern palliative care practice and offers six strategies to enhance time-efficiency in daily clinical care.

Background: Compassion-focused therapy (CFT) has been attracting attention in mental health practice and research. CFT is effective in reducing a variety of negative mental health symptoms. Positive mental health (PMH) focuses on an individual's functioning, quality of life, and well-being, aiming to achieve fulfilment. A need for PMH has been increasingly recognised such as national policies incorporating recovery-oriented approaches. However, how effective CFT is for PMH outcomes remains to be investigated. This narrative review aimed to identify the literature that reports evidence on CFT used against PMH outcomes., Methods: Our research questions (RQs) were as follows: RQ1. What PMH outcomes are targeted in CFT intervention research? RQ2. Is CFT effective for PMH?" Medline, Embase, and PsycINFO were searched on the Ovid platform. All studies that mentioned "compassion focused therapy" and "compassion-focused therapy" were searched., Results: Sixteen RCTs were included published since 2012. Nine studies were from Europe, four from Asia, two from Northern America, and one from Australia and New Zealand. CFT was used for diverse PMH outcomes, and the effects were overall positive. Self-compassion and compassion were the most frequently evaluated outcomes., Conclusions: The mechanism of action for CFT on PMH needs to be evaluated. CFT can be used as part of personal recovery in mental health. More evidence from non-WEIRD countries including LMICs is needed.

Charcot-Marie-Tooth (CMT) disease is a neuromuscular disorder affecting the peripheral nervous system. The diagnostic yield in demyelinating CMT (CMT1) is typically ∼80-95%, of which at least 60% is due to the PMP22 gene duplication. The remainder of CMT1 is more genetically heterogeneous. We used whole exome and whole genome sequencing data included in the GENESIS database to investigate novel causal genes and mutations in a cohort of ∼2,670 individuals with CMT neuropathy. A recurrent heterozygous missense variant p.Thr1424Met in the recently described CMT gene ITPR3, encoding IP3R3 (inositol 1,4,5-trisphosphate receptor 3) was identified. This previously reported p.Thr1424Met change was present in 33 affected individuals from nine unrelated families from multiple populations, representing an unusual recurrence rate at a mutational hotspot, strengthening the gene-disease relationship (GnomADv4 allele frequency 1.76e-6). Sanger sequencing confirmed the co-segregation of the CMT phenotype with the presence of the mutation in autosomal dominant and de novo inheritance patterns, including a four-generation family with multiple affected second-degree cousins. Probands from all families presented with slow nerve conduction velocities, matching the diagnostic category of CMT1. Remarkably, we observed a uniquely variable clinical phenotype for age at onset and phenotype severity in p.Thr1424Met carrying patients, even within families. Finally, we present data supportive of a dominant-negative effect of the p.Thr1424Met mutation with associated changes in protein expression in patient-derived cells., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Cyathostomins are globally important equine parasites, responsible for both chronic and acute pathogenic effects. The occurrence of mixed infections with numerous cyathostomin species hinders our understanding of parasite epidemiology, host-parasite dynamics, and species pathogenicity. There have been few studies of cyathostomin species occurring in horses in Ireland, where temperate climatic conditions with year-round rainfall provide suitable conditions for infection of grazing animals with bursate nematodes. Here, we amplified and sequenced the ITS-2 region of adult worms harvested at post-mortem from eleven adult horses between August 2018 and June 2020, and recorded species prevalence and abundance of worms recovered from the caecum, right ventral colon and left dorsal colon, using both BLAST and IDTAXA for taxonomic attribution. Phylogenetic relationships and community composition were also recorded and compared with other relevant studies, including a global meta-analysis. Overall, our results agree with previous studies that there does not seem to be a major difference in cyathostomin species occurrence in equids in different geographical regions. We confirmed the results of other workers in relation to the difficulties in discriminating between Cylicostephanus calicatus and Coronocyclus coronatus on the basis of ITS-2 sequences., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Coordinated Specialty Care (CSC) is an evidence-based model for early intervention of first episode psychosis (FEP). Monitoring fidelity to CSC models is essential for proper evaluation of program outcomes and quality improvement. To address variability across CSC programs and fidelity assessment-associated burden, an adapted fidelity scale was developed and implemented statewide in Pennsylvania. This report describes the design and preliminary performance of the adapted scale. The Pennsylvania FEP Fidelity Scale (PA-FEP-FS) assesses adherence to the CSC model by focusing on essential model components of other established fidelity scales, in tandem with program evaluation data. Initial data from fourteen PA-FEP sites from 2018 to 2021 were examined as preliminary validation. Assessment-associated burdens and costs were also estimated. PA-FEP-FS captured essential components of CSC models and proved feasible for implementation across varying program structures, while minimizing burden and cost. Programs utilized annual feedback as CSC benchmarks, evidenced by increased scores over time. PA-FEP-FS provides a model for adapting CSC fidelity scales to meet state- or local-level requirements while reducing assessment burdens and costs that may be associated with existing scales., (© 2023. Society for Prevention Research.)

This study seeks to use examine the utility of recently published, developmentally informed measures of parental active tracking for work on youth health behaviors. Information on parental active tracking and health behaviors were collected in six independent survey studies ( n 's = 157-408). A series of empirical questions regarding parental active tracking were examined. The recently published measures of parental active tracking in high school and college were shown to have sufficient internal consistency, to be well described by single latent factors, to be empirically distinct from helicopter parenting, to be inconsistently linked with youth risk behaviors, and to demonstrate closer linkages with youth substance use when accounting for parental motivations for tracking. The measures of parental active tracking employed provide face valid, psychometrically sound, and empirically supported indices for use examining parental influences during adolescence and young adulthood., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

High levels of psychological distress present a major public health issue among LGBTQ+ youth and adults; however, research has repeatedly identified community connectedness as an important protective factor for mental health in LGBTQ+ populations. The aim of the present study was to examine whether age moderates the association of community connectedness on psychological distress in a community sample of LGBTQ+ people. In the present exploratory study, we analyzed secondary cross-sectional data from a sample of LGBTQ+ youth and adults ( n = 292) in a semi-rural community in the Western United States. Participants completed a measure of community connectedness, the K6, and the PHQ-4. The results of two moderation models showed that the negative association of community connectedness on psychological distress was strongest among youth, weaker among young adults, and nonsignificant among older middle-aged adults and older adults. These results provide further evidence for the potential buffering role of community connectedness on psychological distress for LGBTQ+ youth and young adults.

Context: The COVID-19 pandemic presented unique challenges for health care systems. Overcrowded units, extreme illness severity, uncertain prognoses, and mistrust in providers resulted in a "pressure cooker" where traditional communication strategies were often insufficient., Objectives: Building on well-studied traditional communication interventions, neurobiology principles were used to create a novel communication strategy designed in the COVID-ICU to respond to the unique communication needs of patients within the context of a high mistrust setting., Methods: The hierarchy of communication needs recognizes three specific levels of communication that are essential within high-emotion and low-trust settings. The first level is to establish trust. The second level is to resonate with patients' emotions, helping to reduce arousal and improve empathy. The third level includes the more traditional content of disclosing prognostic information and shared decision-making. When facing communication challenges, clinicians are taught to move back a level and reattune to emotions and/or reestablish trust., Discussion: The COVID pandemic revealed the shortcomings of a primarily cognitive communication style. The hierarchy of communication needs emphasizes trust building, and emotional resonance as prerequisites of effective cognitive discussions, resulting in more effective clinician-patient communication that more fully incorporates cultural humility and better meets the needs of diverse patient populations. Additional research is needed to further develop this strategy and evaluate its impact on patient experience and outcomes., Competing Interests: No competing financial interests exist., (© Daniel Neves Forte et al., 2024; Published by Mary Ann Liebert, Inc.)

Purpose: In light of disparities in breast cancer care and outcomes, we explored whether attention to fertility, genetic, and emotional health concerns, as well as satisfaction with care, differs by race/ethnicity among young breast cancer patients. Methods: The Young and Strong Study was a cluster randomized trial of an intervention for patients and providers at 54 U.S. oncology practices enrolling women diagnosed with breast cancer at ≤45 years of age. Provider attention to fertility, genetics, and emotional health was evaluated by medical record review. The proportions of patients with attention to these concerns were compared by race/ethnicity (Hispanic, non-Hispanic Black [NHB], Asian, non-Hispanic White [NHW], or multiracial/other). Satisfaction with care was assessed with the Patient Satisfaction Questionnaire-18 (PSQ-18) at 3 months, with median scores for each of 7 PSQ-18 subscales (general satisfaction, interpersonal manner, communication, financial, time spent with doctor, accessibility, and technical quality) compared by race/ethnicity. Results: Among 465 patients, median age at diagnosis was 40; 6% were Hispanic, 11% NHB, 4% were Asian, 75% NHW, and 3% multiracial/other. Provider attention to genetics, emotional health, and fertility did not differ by race/ethnicity. Median PSQ-18 scores did not differ by race/ethnicity, with median subscale scores ranging from 3.0 to 4.5 across groups, indicating high levels of satisfaction. Conclusion: Satisfaction with care and provider attention to age-specific concerns were similar across racial/ethnic groups among young patients enrolled in an educational and supportive care intervention study. These data suggest that high-quality, equitable care is feasible. Further care delivery research is warranted in more diverse patient and practice settings. Clinical Trial Registration number: NCT01647607.

Context: The majority of people with serious health-related suffering in low- and middle-income countries lack access to palliative care (PC). Increased access to PC education is greatly needed., Objectives: This paper describes the process to adapt an advanced PC training course for a Chilean context., Methods: A joint team of intercultural PC educators from the US and Chile conducted a series of key informant interviews and a target audience survey to iteratively design a PC training course in Chile., Results: Eight key informant interviews identified a strong need for formal PC education pathways, confirmed the five central learning domains, and helped to identify potential course sub-topics. A target audience survey of 59 PC providers from across Chile confirmed a strong desire to participate in such a course., Conclusion: Our team of intercultural PC educators adapted an advanced PC course to the unique context of Chilean providers., Competing Interests: The authors declare that there is no conflict of interest., (© The Author(s), 2023.)

With the development of the COVID-19 vaccine in late 2020, the importance of understanding the drivers of vaccine acceptance and vaccine hesitancy is important for the health of American Indian and Alaska Native communities. We conducted a cross-sectional, anonymous survey in October 2021 using established quantitative methods of virtual surveys to reach tribal members living on three reservations in the Great Plains (N = 679). We conducted multivariate analyses using logistic regression to assess the association between independent variables and COVID-19 vaccination status after adjusting for confounding. Respondents were more likely to have received a COVID-19 vaccine if they were older, had a full-time job, had previously received a flu vaccination, reported a higher level of trust in the health care system, had increased access to vaccinations, were able to isolate, or if they held a desire to keep their family safe. This study is one of the first to offer insights into the associations and possible determinants of COVID-19 vaccine uptake among American Indians in the Great Plains and was completed as part of the National Institutes of Health Rapid Acceleration of Diagnostics of Underserved Populations consortium. We identified a set of demographic, socioeconomic, and motivational factors that are associated with COVID-19 vaccination uptake among Great Plains American Indians and Alaska Natives. It is possible that future vaccine uptake may be enhanced through economic development, strengthening health care operations and care quality, and focusing vaccination messaging on family and community impact., (© 2023. W. Montague Cobb-NMA Health Institute.)

The non-filarial and non-communicable disease podoconiosis affects around 4 million people and is characterized by severe leg lymphedema accompanied with painful intermittent acute inflammatory episodes, called acute dermatolymphangioadenitis (ADLA) attacks. Risk factors have been associated with the disease but the mechanisms of pathophysiology remain uncertain. Lymphedema can lead to skin lesions, which can serve as entry points for bacteria that may cause ADLA attacks leading to progression of the lymphedema. However, the microbiome of the skin of affected legs from podoconiosis individuals remains unclear. Thus, we analysed the skin microbiome of podoconiosis legs using next generation sequencing. We revealed a positive correlation between increasing lymphedema severity and non-commensal anaerobic bacteria, especially Anaerococcus provencensis, as well as a negative correlation with the presence of Corynebacterium, a constituent of normal skin flora. Disease symptoms were generally linked to higher microbial diversity and richness, which deviated from the normal composition of the skin. These findings show an association of distinct bacterial taxa with lymphedema stages, highlighting the important role of bacteria for the pathogenesis of podoconiosis and might enable a selection of better treatment regimens to manage ADLA attacks and disease progression., (© 2023. Springer Nature Limited.)

Background: Podoconiosis, a non-infectious disease originating from long-term exposure of bare feet to irritant red clay soil is a lifelong, disabling disease with no specific diagnostic tool, classified into 5 stages based on the severity of leg swelling (lymphoedema). Secondary bacterial infections have been suggested to cause acute dermatolymphangioadenitis (ADLA) attacks and drive disease progression. Although the North West Region of Cameroon has a proven history of podoconiosis endemicity, the bacterial composition of lymphoedema due to this condition has not been studied. Thus, this study investigated the leg bacterial diversity of patients who suffered from the lymphoedema and their susceptibility pattern to selected antibiotics., Methods: A cross-sectional study was carried out in which podoconiosis affected and non-lymphoedema individuals living in the same community were purposively selected. Samples were collected by swabbing the skin between the toes and around the anklebone, then cultured and sub-cultured on nutrient agar to obtain pure isolates. The cultured isolates were then morphologically and biochemically classified using microscopy and analytic profile index test kits, respectively. The disk diffusion technique was used to determine antibiotic susceptibility., Results: Thirty-three participants were recruited, and 249 bacterial isolates were characterized into 29 genera, 60 species; with 30 (50%) being gram positive rods, 19 (31.7%) gram positive cocci, and 11 (18.3%) gram negative rods. Thirteen gram positive rods, fifteen gram positive cocci, and eight gram negative rods of bacterial species were found only in podoconiosis individuals among which Cellulomonas spp / Microbacterium spp. (2.8%), Staphylococcus lentus (3.3%), and Burkholderia cepacia (4.0%) dominated. 90% (90%) of the bacterial isolates were sensitive to doxycycline, whereas ampicillin had a high level of intermediate resistance, and penicillin G had the greatest resistant profile., Conclusion: Our findings show that 94 (37.8%) out of 249 described bacterial isolates were exclusively found in the legs of podoconiosis individuals, and their susceptibility pattern to antibiotics was similar to that of others., (© 2023. The Author(s).)

Purpose: To explore the perspectives on patient and family needs during cancer treatment and survivorship of American Indian (AI) cancer survivors, caregivers, Tribal leaders, and healers., Participants & Setting: 36 AI cancer survivors from three reservations in the Great Plains region., Methodologic Approach: A community-based participatory research design was employed. Postcolonial Indigenous research techniques of talking circles and semistructured interviews were used to gather qualitative data. Data were analyzed using content analysis to identify themes., Findings: The overarching theme of accompaniment was identified. The following themes were intertwined with this theme: (a) the need for home health care, with the subthemes of family support and symptom management; and (b) patient and family education., Implications for Nursing: To provide high-quality cancer care to AI patients in their home communities, oncology clinicians should collaborate with local care providers, relevant organizations, and the Indian Health Service to identify and develop essential services. Future efforts must emphasize culturally responsive interventions in which Tribal community health workers serve as navigators to accompany patients and families during treatment and in survivorship.

Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.