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Objective: Music strongly modulates our autonomic nervous system. This modulation is evident in musicians' beat-to-beat heart (RR) intervals, a marker of heart rate variability (HRV), and can be related to music features and structures. We present a novel approach to modeling musicians' RR interval variations, analyzing detailed components within a music piece to extract continuous music features and annotations of musicians' performance decisions., Methods: A professional ensemble (violinist, cellist, and pianist) performs Schubert's Trio No. 2, Op. 100, Andante con moto nine times during rehearsals. RR interval series are collected from each musician using wireless ECG sensors. Linear mixed models are used to predict their RR intervals based on music features (tempo, loudness, note density), interpretive choices (Interpretation Map), and a starting factor., Results: The models explain approximately half of the variability of the RR interval series for all musicians, with R-squared = 0.606 (violinist), 0.494 (cellist), and 0.540 (pianist). The features with the strongest predictive values were loudness, climax, moment of concern, and starting factor., Conclusions: The method revealed the relative effects of different music features on autonomic response. For the first time, we show a strong link between an interpretation map and RR interval changes. Modeling autonomic response to music stimuli is important for developing medical and non-medical interventions. Our models can serve as a framework for estimating performers' physiological reactions using only music information that could also apply to listeners., 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., (Copyright © 2024 Soliński, Reed and Chew.)

Upper limb weakness following stroke poses a significant global psychosocial and economic burden. Non-invasive brain stimulation (NIBS) is a potential adjunctive treatment in rehabilitation. However, traditional approaches to rebalance interhemispheric inhibition may not be effective for all patients. The supportive role of the contralesional hemisphere in recovery of upper limb motor function has been supported by animal and clinical studies, particularly for those with severe strokes. This review aims to provide an overview of the facilitation role of the contralesional hemisphere for post-stroke motor recovery. While more studies are required to predict responses and inform the choice of NIBS approach, contralesional facilitation may offer new hope for patients in whom traditional rehabilitation and NIBS approaches have failed.

Purpose: To investigate the spatial distribution of reticular pseudodrusen (RPD) in eyes with age-related macular degeneration (AMD) and their correlation with functional measures, retinal thickness, and changes over time., Design: Longitudinal, cohort study., Participants: Thirty-five participants with RPD and spectrum of AMD severity (including no AMD)., Methods: Multimodal imaging was graded by a reading center, including evaluation of color fundus imaging to assess AMD severity scores. Reticular pseudodrusen presence on OCT volumes was confirmed on en face imaging and the RPD extent was contoured on infrared images. One study eye per participant underwent rod-mediated dark adaptation, measuring rod intercept time (RIT) at 5° and, if needed, 12° superior to the fovea., Main Outcome Measures: The primary outcome was RIT and OCT thickness measures which were correlated with RPD area., Results: A total of 51 eyes had ≥ 1 visit with RPD detected (mean follow-up, 2.19 ± 2.04 years; range, 0-5 years), totaling 169 eye-based visits with RPD. Of the 51 eyes with RPD, 5 (9.8%) developed geographic atrophy and 17 (33.3%) progressed to neovascular AMD. Larger RPD areas were detected more frequently in AMD severity scores 6-7. Reticular pseudodrusen area within an eye generally increased over time. The lesion distribution showed a predilection for the superior retina, especially the outer superior subfield of the ETDRS grid, with the central subfield having least involvement. Reticular pseudodrusen area was inversely correlated with central subfield thickness and positively correlated with RIT at 5° (P = 0.001; r 2  = 0.01) and 12° (P = 0.004; r 2  = 0.01). Rod-mediated dark adaptation at 5° reached the test ceiling in > 85% of visits, irrespective of RPD lesion presence/absence at the test location. Retinal thickness decreased monotonically, with the central subfield demonstrating the greatest percentage change over 5 years (Δ = -5.47%)., Conclusions: In AMD, RPD involve predominantly the superior retina but can involve all ETDRS subfields and evolve over time. Eyes with RPD exhibit structural and functional impairments that can be measured beyond the boundaries of the RPD lesions, suggesting changes associated with RPD are associated with both local changes and a more widespread process., Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2024. Published by Elsevier Inc.)

Neurotomy interrupts the stretch reflex and can be used for the treatment of spasticity. We hypothesized that neurotomy with nerve repair reduces spasticity while preserving motor function due to the preferential recovery of efferent over afferent fibres. This study reports the 1-year outcomes of neurotomy and immediate repair of the musculocutaneous nerve in the proximal arm for treatment of elbow flexor spasticity, comparing these to outcomes in the literature for neurectomy without nerve repair. A total of 10 adult patients with spasticity of the elbow flexors from stroke or traumatic brain injury who had undergone neurotomy and immediate repair of the musculocutaneous nerve were prospectively studied. The results suggest that this procedure effectively reduces elbow flexor spasticity, improves elbow resting position, active elbow extension and is useful for achieving patient goals with effects lasting at least 12 months. Level of evidence: IV (therapeutic)., 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.

Objective: To evaluate the clinical efficacy and cost-effectiveness of telemonitored self-directed rehabilitation (TR) compared with hospital-based rehabilitation (HBR) for patients with total knee arthroplasty (TKA)., Design: In this randomized, non-inferiority clinical trial, 114 patients with primary TKA who were able to walk independently preoperatively were randomized to receive HBR (n = 58) or TR (n = 56). HBR comprised at least five physical therapy sessions over 10 weeks. TR comprised a therapist-led onboarding session, followed by a 10-week unsupervised home-based exercise program, with asynchronous monitoring of rehabilitation outcomes using a telemonitoring system. The primary outcome was fast-paced gait speed at 12 weeks, with a non-inferiority margin of 0.10 m/s. For economic analysis, quality-adjusted-life-years (QALY) was the primary economic outcome (non-inferiority margin, 0.027 points)., Results: In Bayesian analyses, TR had >95% posterior probability of being non-inferior to HBR in gait speed (week-12 adjusted TR-HBR difference, 0.02 m/s; 95%CrI, -0.05 to 0.10 m/s; week-24 difference, 0.01 m/s; 95%CrI, -0.07 to 0.10 m/s) and QALY (0.006 points; 95%CrI, -0.006 to 0.018 points). When evaluated from a societal perspective, TR was associated with lower mean intervention cost (adjusted TR-HBR difference, -S$227; 95%CrI, -112 to -330) after 24 weeks, with 82% probability of being cost-effective compared with HBR at a willingness to pay of S$0/unit of effect for the QALYs., Conclusions: In patients with uncomplicated TKAs and relatively good preoperative physical function, home-based, self-directed TR was non-inferior to and more cost-effective than HBR over a 24-week follow-up period. TR should be considered for this patient subgroup., (Copyright © 2023 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Background: Breast cancer is the most common female malignancy worldwide and a major cause of morbidity and mortality. Exercise during adjuvant treatment improves function and relieves symptoms in breast cancer survivors. However, it is unclear if an unsupervised exercise programme may be as effective as a supervised multimodal group. We investigated the feasibility and efficacy of a centre-based multidimensional rehabilitation (MDR) programme for breast cancer survivors undergoing adjuvant treatment and compared it to an unsupervised home-based exercise (HE) programme., Methods: Participants were self-allocated to either MDR or HE group. MDR participants underwent 24 supervised exercise classes and 10 education classes over 12 weeks. HE participants were instructed on a home exercise regime. Outcome measures, including the 6-min walk test (6MWT) and Frenchay Activities Index (FAI), FACT-Cognitive Function scale, and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30, were conducted at baseline (W0), post-intervention (W12) and 6-months post-intervention (M6). Variance between time points and the 2 groups were analysed using a linear mixed model (unstructured covariance matrix) and adjusted with Bonferroni., Result: Twenty-five participants attended at least half of the MDR interventions, while 21 completed the HE interventions. The former showed significant improvement in 6MWT, from 406.88 m (W0) to 443.34 m (W12) to 452.81 m (M6), while the improvement in the HE group was not significant (407.67 m (W0) to 433.14 m (W12) to 430.96 m (M6)). Both groups showed a significant improvement in FAI, with earlier significant improvement noted at W12 in the MDR group (22.71 (W0) to 27.65 (W12) to 28.81 (M6)) compared to the HE group (23.16 (W0) to 26.47 (W12) to 29.85 (M6)). Dropout rate was 16% in the MDR group and 34% in HE group. Overall satisfaction with the MDR programme was high., Conclusion: Both MDR and HE programmes were feasible. MDR was superior in improving endurance and earlier return to instrumental activities for those who completed at least half of the sessions. Future studies could explore use of technology to improve adherence to exercise., Trial Registration: The study was registered with ClinicalTrial.gov on 01/04/2022 with the registration number NCT05306808., (© 2024. The Author(s).)

Cardiovascular disease is the leading cause of morbidity and mortality in patients with autoimmune rheumatic diseases. Much of this may be attributed to systemic inflammation resulting in coronary atherosclerosis and myocarditis. Cardiac magnetic resonance imaging is the gold standard for the evaluation of cardiac structure and function, including tissue characterization, which allows for detection of myocardial edema, inflammation, and fibrosis. Advances in parametric mapping and coronary flow reserve measurement techniques have the potential to change the diagnosis, risk stratification, and management of patients with autoimmune rheumatic diseases. We provide an overview of the current evidence and suggest potential future roles for the use of comprehensive cardiac magnetic resonance in patients with autoimmune rheumatic diseases in the field of cardio-rheumatology., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier B.V.)

Vitamin D has important anti-inflammatory, anti-microbial properties and plays a central role in the host immune response. Due to the crucial role of the kidneys in the metabolism of vitamin D, patients with chronic kidney disease (CKD) are prone to vitamin D deficiency. The resultant reduction in the production of calcitriol, the activated form of vitamin D, in patients with CKD is responsible for exacerbating the existing renal impairment and periodontal inflammation. Recent evidence suggests a bidirectional, causal relationship between periodontitis and renal functional status. Both conditions have shared pathophysiological mechanisms including oxidative stress, increases in the systemic inflammatory burden and impaired host response. This review explores the association between vitamin D, CKD and periodontitis. The review summarises the current evidence base for the classical and non-classical vitamin D metabolic pathways, the biological mechanisms linking vitamin D deficiency, CKD and periodontitis, as well as the bidirectional relationship between the two chronic inflammatory conditions. Finally, the paper explores the impact of vitamin D deficiency on CKD, periodontitis, and related co-morbidities.

Topic: To review clinical evidence on systemic factors that might be relevant to update diabetic retinal disease (DRD) staging systems, including prediction of DRD onset, progression, and response to treatment., Clinical Relevance: Systemic factors may improve new staging systems for DRD to better assess risk of disease worsening and predict response to therapy., Methods: The Systemic Health Working Group of the Mary Tyler Moore Vision Initiative reviewed systemic factors individually and in multivariate models for prediction of DRD onset or progression (i.e., prognosis) or response to treatments (prediction)., Results: There was consistent evidence for associations of longer diabetes duration, higher glycosylated hemoglobin (HbA1c), and male sex with DRD onset and progression. There is strong trial evidence for the effect of reducing HbA1c and reducing DRD progression. There is strong evidence that higher blood pressure (BP) is a risk factor for DRD incidence and for progression. Pregnancy has been consistently reported to be associated with worsening of DRD but recent studies reflecting modern care standards are lacking. In studies examining multivariate prognostic models of DRD onset, HbA1c and diabetes duration were consistently retained as significant predictors of DRD onset. There was evidence of associations of BP and sex with DRD onset. In multivariate prognostic models examining DRD progression, retinal measures were consistently found to be a significant predictor of DRD with little evidence of any useful marginal increment in prognostic information with the inclusion of systemic risk factor data apart from retinal image data in multivariate models. For predicting the impact of treatment, although there are small studies that quantify prognostic information based on imaging data alone or systemic factors alone, there are currently no large studies that quantify marginal prognostic information within a multivariate model, including both imaging and systemic factors., Conclusion: With standard imaging techniques and ways of processing images rapidly evolving, an international network of centers is needed to routinely capture systemic health factors simultaneously to retinal images so that gains in prediction increment may be precisely quantified to determine the usefulness of various health factors in the prognosis of DRD and prediction of response to treatment., Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (© 2024 by the American Academy of Ophthalmology.)

Objective. Motor imagery (MI) brain-computer interfaces (BCIs) based on electroencephalogram (EEG) have been developed primarily for stroke rehabilitation, however, due to limited stroke data, current deep learning methods for cross-subject classification rely on healthy data. This study aims to assess the feasibility of applying MI-BCI models pre-trained using data from healthy individuals to detect MI in stroke patients. Approach. We introduce a new transfer learning approach where features from two-class MI data of healthy individuals are used to detect MI in stroke patients. We compare the results of the proposed method with those obtained from analyses within stroke data. Experiments were conducted using Deep ConvNet and state-of-the-art subject-specific machine learning MI classifiers, evaluated on OpenBMI two-class MI-EEG data from healthy subjects and two-class MI versus rest data from stroke patients. Main results. Results of our study indicate that through domain adaptation of a model pre-trained using healthy subjects' data, an average MI detection accuracy of 71.15% (±12.46%) can be achieved across 71 stroke patients. We demonstrate that the accuracy of the pre-trained model increased by 18.15% after transfer learning ( p <0.001). Additionally, the proposed transfer learning method outperforms the subject-specific results achieved by Deep ConvNet and FBCSP, with significant enhancements of 7.64% ( p <0.001) and 5.55% ( p <0.001) in performance, respectively. Notably, the healthy-to-stroke transfer learning approach achieved similar performance to stroke-to-stroke transfer learning, with no significant difference ( p >0.05). Explainable AI analyses using transfer models determined channel relevance patterns that indicate contributions from the bilateral motor, frontal, and parietal regions of the cortex towards MI detection in stroke patients. Significance. Transfer learning from healthy to stroke can enhance the clinical use of BCI algorithms by overcoming the challenge of insufficient clinical data for optimal training., (© 2024 IOP Publishing Ltd.)

Research has shown the effectiveness of motor imagery in patient motor rehabilitation. Transcranial electrical stimulation has also demonstrated to improve patient motor and non-motor performance. However, mixed findings from motor imagery studies that involved transcranial electrical stimulation suggest that current experimental protocols can be further improved towards a unified design for consistent and effective results. This paper aims to review, with some clinical and neuroscientific findings from literature as support, studies of motor imagery coupled with different types of transcranial electrical stimulation and their experiments onhealthy and patient subjects. This review also includes the cognitive domains of working memory, attention, and fatigue, which are important for designing consistent and effective therapy protocols. Finally, we propose a theoretical all-inclusive framework that synergizes the three cognitive domains with motor imagery and transcranial electrical stimulation for patient rehabilitation, which holds promise of benefiting patients suffering from neuromuscular and cognitive disorders.

Background: Differentiating tumefactive demyelinating lesions (TDL) from neoplasms of the central nervous system continues to be a diagnostic dilemma in many cases., Objective: Our study aimed to examine and contrast the clinical and radiological characteristics of TDL, high-grade gliomas (HGG) and primary CNS lymphoma (CNSL)., Method: This was a retrospective review of 66 patients (23 TDL, 31 HGG and 12 CNSL). Clinical and laboratory data were obtained. MRI brain at presentation were analyzed by two independent, blinded neuroradiologists., Results: Patients with TDLs were younger and predominantly female. Sensorimotor deficits and ataxia were more common amongst TDL whereas headaches and altered mental status were associated with HGG and CNSL. Compared to HGG and CNSL, MRI characteristics supporting TDL included relatively smaller size, lack of or mild mass effect, incomplete peripheral rim enhancement, absence of central enhancement or restricted diffusion, lack of cortical involvement, and presence of remote white matter lesions on the index scan. Paradoxically, some TDLs may present atypically or radiologically mimic CNS lymphomas., Conclusion: Careful evaluation of clinical and radiological features helps in differentiating TDLs at first presentation from CNS neoplasms., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Functional recovery and return to work (RTW) after stroke are important rehabilitation goals that have significant impact on quality of life. Comparisons of functional outcomes and RTW between ischemic stroke (IS) and hemorrhagic stroke (HS), especially among young adults with stroke, have either been limited or yielded inconsistent results. We aimed to assess functional outcomes and ability to RTW in young adults with IS and HS, specifically primary spontaneous intracranial hemorrhage (SICH)., Methods: Young adults with IS or SICH aged 18-50-years-old were included. Outcome measures were modified Rankins score (mRS) on discharge and 3-months and RTW at 3-months after stroke. Good functional outcome was defined as an mRS of 0-2., Results: We included 459 patients (71.5% male) with a mean age of 43.3 ± 5.7 years, comprising 49.2% IS and 50.8% SICH. Patients with SICH were more likely to have unfavourable shifts in ordinal mRS on discharge (OR 7.52, CI 5.18-10.87, p < 0.001) and at 3-months (OR 6.41, CI 4.17-9.80, p < 0.001). Patients with IS more likely achieved good functional outcomes (80.2% vs. 51.8%, p < 0.001) and were able to RTW at 3-months (54.4% vs. 36.3%, p = 0.004). Among all stroke patients with good functional outcomes, one-third did not RTW at 3-months. Patients with longer length of hospitalisation and higher National Institutes of Health Stroke Scale (NIHSS) score on admission, especially in the domain categories of level of consciousness, vision, motor function, language and neglect, were less likely to RTW at 3-months., Conclusion: Patients with IS were more likely to RTW when compared to SICH patients. Many young stroke patients did not RTW despite good functional outcomes. Further research should therefore address differences in prognosis and identify predictors that influence ability to RTW after stroke in the young adult population., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Postpartum depression (PPD) is a public health problem that is associated with detrimental effects on the wellbeing of the mother, child and family. Early detection for PPD at the primary health level provides an opportunity for intervention. We aim to examine: (1) the prevalence rate of PPD in the primary care population, (2) acceptance and attendance rates of intervention for women who screened positive for PPD, (3) sociodemographic and maternal risk factors of PPD, and (4) the impact of PPD on breastfeeding. We implemented a mother-child dyadic screening program using the modified Patient Health Questionnaire-2 during routine well-child visits at 2 or 3 months postpartum between July 2019 and December 2021. We performed multivariable logistic regression to identify independent risk factors for PPD and described using adjusted odds ratio (OR) with corresponding 95 % confidence intervals. Among 5561 mothers, the prevalence rate of probable PPD was 2.4 %. About half (54.4 %) of mothers who screened positive accepted intervention and of these, about two-thirds accepted onward referrals to tertiary care and community mental health service, with higher attendance at the latter. In the final adjusted model, mothers who had probable PPD were more likely to be older than age 35 years (OR 1.88, 95 % CI 1.05-3.45; p < 0.05) and not breastfeeding (OR 1.9, 95 % CI 1.06-3.38; p < 0.05). Overall, our findings highlight the importance of early PPD screening and management in primary care. These findings can help inform maternal mental health service development and utilization, thereby optimizing maternal and infant outcomes., Competing Interests: Declaration of Competing Interest All the authors declare no conflict of interests., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Topic: Several patient-reported outcome measures (PROMs) are available to measure health-related quality of life (HRQoL) in patients with late-stage clinical diabetic retinal diseases (DRDs). However, an understanding of the psychometric properties of PROMs is needed to assess how they could relate to severity levels of a revised DRD grading system. This narrative review assessed the available generic-, vision-, and DRD-related PROMs used in DRD research and highlights areas for improvement., Clinical Relevance: Diabetic retinal disease is a common complication of diabetes and can lead to sight-threatening complications with a devastating effect on HRQoL., Methods: The Quality of Life working group is one of 6 working groups organized for the DRD Staging System Update Effort, a project of the Juvenile Diabetes Research Foundation Mary Tyler Moore Vision Initiative. PubMed, Cochrane Library, Embase, and Google Scholar databases were searched using core keywords to retrieve ophthalmology-related review articles, randomized clinical trials, and prospective, observational, and cross-sectional studies in the English language. A detailed review of 12 PROMs (4 QoL questionnaires and 8 utilities) that met a minimum level of evidence (LOE) was conducted. The relevance of each PROM to DRD disease stage and Biomarker Qualification guidelines ( Biomarkers, EndpointS, and other Tools ) categories was also defined., Results: The National Eye Institute 25-item Visual Function Questionnaire (NEI VFQ-25), Impact of vision impairment-computerized adaptive testing, and Diabetic Retinopathy and Macular Edema Computerized Adaptive Testing System had a LOE of II in detecting change due to late-stage DRD (diabetic macular edema), although several areas for improvement (e.g., psychometrics and generalizability) were identified. Other PROMs, particularly the utilities, had a LOE of III due to cross-sectional evidence in late-stage clinical DRD. Although the NEI VFQ-25 has been the most widely used PROM in late-stage DRD, more work is required to improve its multidimensional structure and other psychometric limitations. No PROM was deemed relevant for subclinical or early/mid-DRD., Conclusion: This narrative review found that the most commonly used PROM is NEI VFQ-25, but none meets the ideal psychometric, responsiveness, and clinical setting digital administration requirements that could be included in an updated DRD staging system for diagnosis and monitoring of DRD progression., Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (© 2023 Published by Elsevier Inc. on behalf of the American Academy of Ophthalmology.)

Background and Objective: The purpose of this study was to describe statewide perinatal quality improvement (QI) activities, specifically implementation of Alliance for Innovation on Maternal Health (AIM) patient safety bundles and use of teamwork and communication tools in obstetric units in Oklahoma and Texas., Methods: In January-February 2020, we conducted a survey of AIM-enrolled hospitals in Oklahoma (n = 35) and Texas (n = 120) to gather data on obstetric unit organization and QI processes. Data were linked to hospital characteristics information from the 2019 American Hospital Association survey and hospitals' maternity levels of care from state agencies. We generated descriptive statistics for each state and created an index to summarize adoption of QI processes. We fitted linear regression models to examine how this index varied by hospital characteristics and self-reported ratings for patient safety and AIM bundle implementation., Results: Most obstetric units had standardized clinical processes for obstetric hemorrhage (94% Oklahoma; 97% Texas), massive transfusion (94% Oklahoma; 97% Texas), and severe hypertension in pregnancy (97% Oklahoma; 80% Texas); regularly conducted simulation drills for obstetric emergencies (89% Oklahoma; 92% Texas); had multidisciplinary QI committees (61% Oklahoma; 83% Texas); and conducted debriefs after major obstetric complications (45% Oklahoma; 86% Texas). Few obstetric units offered recent staff training on teamwork and communication to their staff (6% Oklahoma; 22% Texas); those who did were more likely to employ specific strategies to facilitate communication, escalate concerns, and manage staff conflicts. Overall, adoption of QI processes was significantly higher in hospitals in urban than rural areas, teaching than nonteaching, offering higher levels of maternity care, with more staff per shift, and greater delivery volume (all P < .05). The QI adoption index scores were strongly associated with respondents' ratings for patient safety and implementation of maternal safety bundles (both P < .001)., Conclusions: Adoption of QI processes varies across obstetric units in Oklahoma and Texas, with implications for implementing future perinatal QI initiatives. Notably, findings highlight the need to reinforce support for rural obstetric units, which often face greater barriers to implementing patient safety and QI processes than urban units., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

An increasing body of evidence points to the involvement of the cerebellum in cognition. Specifically, previous studies have shown that the superior and inferior portions of the cerebellum are involved in different verbal working memory (WM) mechanisms as part of two separate cerebro-cerebellar loops for articulatory rehearsal and phonological storage mechanisms. In comparison, our understanding of the involvement of the cerebellum in visual WM remains limited. We have previously shown that performance in verbal WM is disrupted by single-pulse transcranial magnetic stimulation (TMS) of the right superior cerebellum. The present study aimed to expand on this notion by exploring whether the inferior cerebellum is similarly involved in visual WM. Here, we used fMRI-guided, double-pulse TMS to probe the necessity of left superior and left inferior cerebellum in visual WM. We first conducted an fMRI localizer using the Sternberg visual WM task, which yielded targets in left superior and inferior cerebellum. Subsequently, TMS stimulation of these regions at the end of the encoding phase resulted in decreased accuracy in the visual WM task. Differences in the visual WM deficits caused by stimulation of superior and inferior left cerebellum raise the possibility that these regions are involved in different stages of visual WM., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To identify clinicopathological or radiological factors that may predict a diagnosis of upper urinary tract urothelial cell carcinoma (UTUC) to inform which patients can proceed directly to radical nephroureterectomy (RNU) without the delay for diagnostic ureteroscopy (URS)., Patients and Methods: All consecutive patients investigated for suspected UTUC in a high-volume UK centre between 2011 and 2017 were identified through retrospective analysis of surgical logbooks and a prospectively maintained pathology database. Details on clinical presentation, radiological findings, and URS/RNU histopathology results were evaluated. Multivariate regression analysis was performed to evaluate predictors of a final diagnosis of UTUC., Results: In all, 260 patients were investigated, of whom 230 (89.2%) underwent URS. RNU was performed in 131 patients (50.4%), of whom 25 (9.6%) proceeded directly without URS - all of whom had a final histopathological diagnosis of UTUC - and 15 (11.5%) underwent RNU after URS despite no conclusive histopathological confirmation of UTUC. Major surgery was avoided in 77 patients (33.5%) where a benign or alternative diagnosis was made on URS, and 14 patients (6.1%) underwent nephron-sparing surgery. Overall, 178 patients (68.5%) had a final diagnosis of UTUC confirmed on URS/RNU histopathology. On multivariate logistic regression analysis, a presenting complaint of visible haematuria (hazard ratio [HR] 5.17, confidence interval [CI] 1.91-14.0; P = 0.001), a solid lesion reported on imaging (HR 37.8, CI = 11.7-122.1; P < 0.001) and a history of smoking (HR 3.07, CI 1.35-6.97; P = 0.007), were predictive of a final diagnosis of UTUC. From this cohort, 51 (96.2%) of 53 smokers who presented with visible haematuria and who had a solid lesion on computed tomography urogram had UTUC on final histopathology., Conclusion: We identified specific factors which may assist clinicians in selecting which patients may reliably proceed to RNU without the delay of diagnostic URS. These findings may inform a prospective multicentre analysis including additional variables such as urinary cytology., (© 2022 BJU International.)

Primary cardiac involvement in systemic sclerosis (SSc) is an important cause of morbidity and mortality. Abnormalities of cardiac structure and function can be detected on routine cardiopulmonary screening that is the standard of care for SSc monitoring. Cardiovascular magnetic resonance-extracellular volume (indicating diffuse fibrosis) and cardiac biomarkers may identify at-risk patients who would benefit from further evaluation including screening for atrial and ventricular arrhythmias with implantable loop recorders. The role of algorithm-based cardiac evaluation both before and after therapeutic initiation is one of the many unmet needs for SSc clinical care., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: Nephroureterectomy(NU) remains the gold-standard surgical option for the management of upper urinary tract urothelial carcinoma(UTUC). Controversy exists regarding the optimal excision technique of the lower ureter. We sought to compare post-UTUC bladder tumour recurrence across the Scottish Renal Cancer Consortium(SRCC)., Methods: Patients who underwent NU for UTUC across the SRCC 2012-2019 were identified. The impact of lower-end surgical technique along with T-stage, N-stage, tumour location and focality, positive surgical margin, pre-NU ureteroscopy, upper-end technique and adjuvant mitomycin C administration were assessed by Kaplan-Meier and Cox-regression. The primary outcome was intra-vesical recurrence-free survival (B-RFS)., Results: In 402 patients, the median follow-up was 29 months. The lower ureter was managed by open transvesical excision in 90 individuals, transurethral and laparoscopic dissection in 76, laparoscopic or open extra-vesical excision in 31 and 42 respectively, and transurethral dissection and pluck in 163. 114(28.4%) patients had a bladder recurrence during follow-up. There was no difference in B-RFS between lower-end techniques by Kaplan-Meier (p = 0.94). When all factors were taken into account by adjusted Cox-regression, preceding ureteroscopy (HR 2.65, p = 0.001), lower ureteric tumour location (HR 2.16, p = 0.02), previous bladder cancer (HR 1.75, p = 0.01) and male gender (HR 1.61, p = 0.03) were associated with B-RFS., Conclusion: These data suggest in appropriately selected patients, lower ureteric management technique does not affect B-RFS. Along with lower ureteric tumour location, male gender and previous bladder cancer, preceding ureteroscopy was associated with a higher recurrence rate following NU, and the indication for this should be carefully considered., (© 2023. The Author(s).)

Patients with systemic sclerosis and systemic lupus erythematosus serologies present a unique challenge to the clinician when hypertension is detected in the outpatient setting. Treatment choices for non-renal crisis hypertension are different for systemic sclerosis versus systemic lupus erythematosus. Urgent laboratory studies and, in the presence of certain symptoms, imaging assessment are indicated in systemic sclerosis and systemic lupus erythematosus overlap patients with systemic hypertension. Long-term assessment of systemic hypertension may be enhanced by advances in non-contrast imaging that serve as valuable biomarkers for progressive vasculopathy. In this review, the diagnostic approach to systemic sclerosis and systemic lupus erythematosus overlap patients presenting with hypertension is discussed., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

Sleep shortage is a major concern in modern life and induces various psycho-physical disorders, including skin problems. In cosmeceutics, females are aware that sleep deprivation worsens their facial skin tone. Here, we measured the effects of sleep deprivation on facial skin yellowness and examined yellow chromophores, such as bilirubin and carotenoids, in blood serum as potential causes of yellowness. Total sleep deprivation (0 h sleep overnight, N = 28) and repeated partial sleep deprivation (4 h sleep for 5 consecutive days, N = 10) induced significant increases in facial skin yellowness. The higher yellowness was sustained even after both sleep deprivation types stopped. However, circulating levels of yellow chromophores were unchanged in the total sleep deprivation study. Neither circulating interleukin-6 nor urinary biopyrrin levels were affected by total sleep deprivation, suggesting that apparent oxidative stress in the body was not detected in the present total deprivation protocol. Facial redness was affected by neither total nor repeated partial sleep deprivation. Therefore, blood circulation may play a limited role in elevated yellowness. In conclusion, facial skin yellowness was indeed increased by sleep deprivation in our clinical studies. Local in situ skin-derived factors, rather than systemic chromophore change, may contribute to the sleep deprivation-induced elevation of facial skin yellowness.

Background: Trust is of fundamental importance to the adoption of technologies in health care. The increasing use of telemedicine worldwide makes it important to consider user views and experiences. In particular, we ask how the mediation of a technological platform alters the trust relationship between patient and health care provider., Objective: To date, few qualitative studies have focused on trust in the use of remote health care technologies. This study examined the perspectives of patients and clinical staff who participated in a remote blood pressure monitoring program, focusing on their experiences of trust and uncertainty in the use of technology and how this telehealth intervention may have affected the patient-provider relationship., Methods: A secondary qualitative analysis using inductive thematic analysis was conducted on interview data from 13 patients and 8 staff members who participated in a remote blood pressure monitoring program to elicit themes related to trust., Results: In total, 4 themes were elicited that showed increased trust (patients felt reassured, patients trusted the telehealth program, staff felt that the data were trustworthy, and a better patient-provider partnership based on the mutually trusted data), and 4 themes were elicited that reflected decreased trust (patients' distrust of technology, clinicians' concerns about the limitations of technologically mediated interactions, experiences of uncertainty, and institutional risk)., Conclusions: Managing trust relationships plays an important role in the successful implementation of telemedicine. Ensuring that trust building is incorporated in the design of telehealth interventions can contribute to improved effectiveness and quality of care., (©Evelyn Chew, Sok Huang Teo, Wern Ee Tang, David Wei Liang Ng, Gerald Choon Huat Koh, Valerie Hui Ying Teo. Originally published in JMIR Human Factors (https://humanfactors.jmir.org), 05.01.2023.)

Objectives: Despite the availability of cancer rehabilitation, utilization at our institution was low. We designed the Cancer Rehabilitation Questionnaire (CRQ) to investigate the prevalence of functional impairments amongst cancer survivors and attitudes towards rehabilitation participation. We evaluated the performance of CRQ as a screening tool for detecting clinically important physical dysfunction., Design: A cross-sectional study was performed, recruiting cancer survivors at a university outpatient oncology clinic. Cancer survivors completed the CRQ and European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 Questionnaires. Descriptive statistical analysis and receiver operator characteristics analysis were performed to assess the ability of the CRQ to detect clinically important physical dysfunction, as measured by the EORTC QLQ-C30., Results: Of 204 participants, 87.3% reported impairments in at least 1 CRQ domain. Pain and weakness were most common. The number of positive items correlated with EORTC global health status and functional scales. A cut-off of ≥ 4 on the CRQ predicted clinically important physical dysfunction (sensitivity 61.8%, specificity 75.5%). Of those with impairments, 53.9% were unwilling to participate in rehabilitation. Transportation, need for caregivers, and cost were the main barriers., Conclusion: Our findings will guide resource allocation to overcome barriers to participation. The CRQ can help to stratify cancer survivors requiring further rehabilitation interventions.

Background: All patients who underwent curative resection for colorectal cancer (CRC) are frequently reviewed in tertiary institutions to ensure timely detection of any disease recurrence. There has been no local study that evaluated the feasibility of monitoring their condition in the community as a possible new model of care. This study henceforth seeks to understand CRC patients' views and receptiveness of having their surveillance consultations conducted in a community setting., Methods: We convenience sampled Stage I and II CRC patients who were within five years post-operation in the outpatient clinics. An open-ended questionnaire aimed at elucidating their perception towards cancer surveillance in a community setting was administered. Content analysis was used to group and quantify responses from participants., Results: Twenty-five participants agreed to participate in the study. Only 48% of the participants felt that having phlebotomy procedures in a community or home setting was acceptable. Participants were less willing to be reviewed by a physician who is not their primary surgeon, with only 32% agreeable to seeing a different doctor for surveillance if given a choice. However, most participants were open to having a telephone consultation in place of a physical face-to-face consultation before (72%) and after (76%) going through medical imaging., Conclusions: Participants remained keen to be managed by their primary surgeons and were hesitant towards having their follow-up surveillance consultations in community and primary care settings. Further studies should be conducted to understand whether these perceptions are generalisable, and if more can be done to change public perception towards the role of community and primary care institutions., (© 2022. The Author(s).)

Age-related macular degeneration (AMD) is a complex disease with increasing numbers of individuals being afflicted and treatment modalities limited. There are strong interactions between diet, age, the metabolome, and gut microbiota, and all of these have roles in the pathogenesis of AMD. Communication axes exist between the gut microbiota and the eye, therefore, knowing how the microbiota influences the host metabolism during aging could guide a better understanding of AMD pathogenesis. While considerable experimental evidence exists for a diet-gut-eye axis from murine models of human ocular diseases, human diet-microbiome-metabolome studies are needed to elucidate changes in the gut microbiome at the taxonomic and functional levels that are functionally related to ocular pathology. Such studies will reveal new ways to diminish risk for progression of- or incidence of- AMD. Current data suggest that consuming diets rich in dark fish, fruits, vegetables, and low in glycemic index are most retina-healthful during aging., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Ganciclovir (GCV) is widely used in solid organ and haematopoietic stem cell transplant patients for prophylaxis and treatment of cytomegalovirus. It has long been considered a mutagen and carcinogen. However, the contribution of GCV to cancer incidence and other factors that influence its mutagenicity remains unknown., Methods: This retrospective cohort study analysed genomics data for 121,771 patients who had undergone targeted sequencing compiled by the Genomics Evidence Neoplasia Information Exchange (GENIE) or Foundation Medicine (FM). A statistical approach was developed to identify patients with GCV-associated mutational signature (GCV sig ) from targeted sequenced data of tumour samples. Cell line exposure models were further used to quantify mutation burden and DNA damage caused by GCV and other antiviral and immunosuppressive drugs., Results: Mutational profiles from 22 of 121,771 patient samples in the GENIE and FM cohorts showed evidence of GCV sig . A diverse range of cancers was represented. All patients with detailed clinical history available had previously undergone solid organ transplantation and received GCV and mycophenolate treatment. RAS hotspot mutations associated with GCV sig were present in 9 of the 22 samples, with all samples harbouring multiple GCV-associated protein-altering mutations in cancer driver genes. In vitro testing in cell lines showed that elevated DNA damage response and GCV sig are uniquely associated with GCV but not acyclovir, a structurally similar antiviral. Combination treatment of GCV with the immunosuppressant, mycophenolate mofetil (MMF), increased the misincorporation of GCV in genomic DNA and mutations attributed to GCV sig in cell lines and organoids., Conclusions: In summary, GCV can cause a diverse range of cancers. Its mutagenicity may be potentiated by other therapies, such as mycophenolate, commonly co-prescribed with GCV for post-transplant patients. Further investigation of the optimal use of these drugs could help reduce GCV-associated mutagenesis in post-transplant patients., (© 2022. The Author(s).)

Musical prosody is characterized by the acoustic variations that make music expressive. However, few systematic and scalable studies exist on the function it serves or on effective tools to carry out such studies. To address this gap, we introduce a novel approach to capturing information about prosodic functions through a citizen science paradigm. In typical bottom-up approaches to studying musical prosody, acoustic properties in performed music and basic musical structures such as accents and phrases are mapped to prosodic functions, namely segmentation and prominence. In contrast, our top-down, human-centered method puts listener annotations of musical prosodic functions first, to analyze the connection between these functions, the underlying musical structures, and acoustic properties. The method is applied primarily to the exploring of segmentation and prominence in performed solo piano music. These prosodic functions are marked by means of four annotation types-boundaries, regions, note groups, and comments-in the CosmoNote web-based citizen science platform, which presents the music signal or MIDI data and related acoustic features in information layers that can be toggled on and off. Various annotation strategies are discussed and appraised: intuitive vs. analytical; real-time vs. retrospective; and, audio-based vs. visual. The end-to-end process of the data collection is described, from the providing of prosodic examples to the structuring and formatting of the annotation data for analysis, to techniques for preventing precision errors. The aim is to obtain reliable and coherent annotations that can be applied to theoretical and data-driven models of musical prosody. The outcomes include a growing library of prosodic examples with the goal of achieving an annotation convention for studying musical prosody in performed music., 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., (Copyright © 2022 Bedoya, Fyfe and Chew.)

This position paper makes the case for an innovative, multi-disciplinary methodological approach to advance knowledge on the nature and work of music performance, driven by a novel experiential perspective, that also benefits analysis of electrocardiographic sequences. Music performance is considered by many to be one of the most breathtaking feats of human intelligence. It is well accepted that music performance is a creative act, but the nature of its work remains elusive. Taking the view of performance as an act of creative problem solving, ideas in citizen science and data science, optimization, and computational thinking provide means through which to deconstruct the process of music performance in scalable ways. The method tackles music expression's lack of notation-based data by leveraging listeners' perception and experience of the structures elicited by the performer, with implications for data collection and processing. The tools offer ways to parse a musical sequence into coherent structures, to design a performance, and to explore the space of possible interpretations of the musical sequence. These ideas and tools can be applied to other music-like sequences such as electrocardiographic recordings of arrhythmias (abnormal heart rhythms). Leveraging musical thinking and computational approaches to performance analysis, variations in expressions of cardiac arrhythmias can be more finely characterized, with implications for tailoring therapies and stratifying heart rhythm disorders., Competing Interests: The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chew.)

Introduction - Retinal layer segmentation in optical coherence tomography (OCT) images is an important approach for detecting and prognosing disease. Automating segmentation using robust machine learning techniques lead to computationally efficient solutions and significantly reduces the cost of labor-intensive labeling, which is traditionally performed by trained graders at a reading center, sometimes aided by semi-automated algorithms. Although several algorithms have been proposed since the revival of deep learning, eyes with severe pathological conditions continue to challenge fully automated segmentation approaches. There remains an opportunity to leverage the underlying spatial correlations between the retinal surfaces in the segmentation approach. Methods - Some of these proposed traditional methods can be expanded to utilize the three-dimensional spatial context governing the retinal image volumes by replacing the use of 2D filters with 3D filters. Towards this purpose, we propose a spatial-context, continuity and anatomical relationship preserving semantic segmentation algorithm, which utilizes the 3D spatial context from the image volumes with the use of 3D filters. We propose a 3D deep neural network capable of learning the surface positions of the layers in the retinal volumes. Results - We utilize a dataset of OCT images from patients with Age-related Macular Degeneration (AMD) to assess performance of our model and provide both qualitative (including segmentation maps and thickness maps) and quantitative (including error metric comparisons and volumetric comparisons) results, which demonstrate that our proposed method performs favorably even for eyes with pathological changes caused by severe retinal diseases. The Mean Absolute Error (MAE) and Root Mean Squared Error (RMSE) for patients with a wide range of AMD severity scores (0-11) were within 0.84±0.41 and 1.33±0.73 pixels, respectively, which are significantly better than some of the other state-of-the-art algorithms. Conclusion - The results demonstrate the utility of extracting features from the entire OCT volume by treating the volume as a correlated entity and show the benefit of utilizing 3D autoencoder based regression networks for smoothing the approximated retinal layers by inducing shape based regularization constraints., Competing Interests: The authors declare no conflicts of interest.

We report an autosomal recessive, multi-organ tumor predisposition syndrome, caused by bi-allelic loss-of-function germline variants in the base excision repair (BER) gene MBD4. We identified five individuals with bi-allelic MBD4 variants within four families and these individuals had a personal and/or family history of adenomatous colorectal polyposis, acute myeloid leukemia, and uveal melanoma. MBD4 encodes a glycosylase involved in repair of G:T mismatches resulting from deamination of 5'-methylcytosine. The colorectal adenomas from MBD4-deficient individuals showed a mutator phenotype attributable to mutational signature SBS1, consistent with the function of MBD4. MBD4-deficient polyps harbored somatic mutations in similar driver genes to sporadic colorectal tumors, although AMER1 mutations were more common and KRAS mutations less frequent. Our findings expand the role of BER deficiencies in tumor predisposition. Inclusion of MBD4 in genetic testing for polyposis and multi-tumor phenotypes is warranted to improve disease management., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background and Aims: Siblings of colorectal cancer (CRC) patients are at increased risk of developing CRC, but screening rates remain low. Through a randomized behavioral intervention, this study aimed to determine whether patients can advocate screening to their siblings using a tailored educational package., Methods: CRC survivors were recruited and randomized into relaying either tailored materials (intervention group) or existing national screening guidelines (control group) to their siblings. Siblings could respond to the study team if they were interested in learning about CRC screening. Study outcomes were patient advocacy rates (number of patients who had successfully contacted at least 1 eligible sibling) between groups and the proportion of eligible siblings who responded., Results: Between May 2017 and March 2021, 219 CRC patients were randomized to the intervention (n = 110) and control (n = 109) groups. Patient advocacy rates were high and did not differ significantly between groups. However, only 14.3% of eligible siblings (n = 85) responded to the study team. Siblings of patients from the intervention group were more likely to respond (adjusted odds ratio, 1.8; 95% confidence interval, 1.1-3.0; P < .05). Moreover, after controlling for potential confounders, siblings aged ≥60 years were significantly less likely to respond (adjusted odds ratio, .3; 95% confidence interval, .1-.7; P < .01)., Conclusions: CRC patients are willing advocates of screening, and siblings contacted by patients from the intervention group were also more likely to reach out to the study team. However, overall sibling response rates were low despite advocacy, suggesting that patient-led advocacy should at best be used as an adjunct to other, multipronged CRC screening promotion modalities., (Copyright © 2022 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Age-related macular degeneration (AMD) is the leading cause of vision loss. Some patients experience vision loss over a delayed timeframe, others at a rapid pace. Physicians analyze time-of-visit fundus photographs to predict patient risk of developing late-AMD, the most severe form of AMD. Our study hypothesizes that 1) incorporating historical data improves predictive strength of developing late-AMD and 2) state-of-the-art deep-learning techniques extract more predictive image features than clinicians do. We incorporate longitudinal data from the Age-Related Eye Disease Studies and deep-learning extracted image features in survival settings to predict development of late- AMD. To extract image features, we used multi-task learning frameworks to train convolutional neural networks. Our findings show 1) incorporating longitudinal data improves prediction of late-AMD for clinical standard features, but only the current visit is informative when using complex features and 2) "deep-features" are more informative than clinician derived features. We make codes publicly available at https://github.com/bionlplab/AMD&#95;prognosis&#95;amia2021., (©2021 AMIA - All rights reserved.)

Background: Dislocation of the knee is a serious and potentially limb-threatening injury. There are three types of dislocation around the knee joint: patellofemoral, tibiofemoral, and tibiofibular. Tibiofemoral dislocation is the variant that is deemed the most serious, with a higher risk of compromise to the popliteal artery and common peroneal nerve. Although simultaneous dislocations of two types have been described, there has been no such description of all three types occurring simultaneously., Case Presentation: We present a case of a 40-year-old hairdresser who suffered a fall off her moped in Spain, and simultaneously dislocated all three articulations around the knee. Diagnosis was achieved with clinical examination, plain films, and computed tomography and magnetic resonance imaging scans. Management consisted of initial surgical debridement and reduction with stabilization of the affected joints., Conclusion: Dislocation of the knee is an uncommon but life changing and potentially limb-threatening injury. It should always be suspected in trauma patients who present with multiligamentous knee injuries. The main concern is of neurovascular compromise to the lower leg, namely, the popliteal artery and common peroneal nerve. The treatment of multiligamentous knee injuries for most patients is surgical treatment with physiotherapy and adequate stabilization of the knee joint. Close monitoring of progress of the knee in terms of persistent laxity, range of movement, and functional status is required for at least 1-year post injury. Current evidence suggests that, despite good functional outcomes for knee dislocations in the short term, the prevalence of post-traumatic osteoarthritis is high in the long term., (© 2021. The Author(s).)

Background: The SINgapore GERiatric intervention study to reduce cognitive decline and physical frailty (SINGER) randomised controlled trial (RCT) uses a multidomain lifestyle interventions approach, shown to be effective by the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) trial, to delay cognitive decline., Objective: To investigate the efficacy and safety of the SINGER multidomain lifestyle interventions in older adults at risk for dementia to delay cognitive decline., Participants: 1200 participants between 60-77 years old, with Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) dementia risk score ≥6, fulfilling at least one of the following LIBRA index for diet, cognitive activity, physical activity and a Montreal Cognitive Assessment (MoCA) score ≥18, ≤27 points, will be recruited across Singapore., Methods: SINGER is a 2-year multi-site RCT consisting of multidomain interventions: dietary advice, exercise, cognitive training, and vascular risk factors management. Participants will be randomised into either the Self-Guided Intervention (SGI; general lifestyle and health information and resources) or Structured Lifestyle Intervention (SLI) group. The SLI comprises diet training (6 group and 3 individual sessions over 12 months); exercise (supervised: 1-hour twice weekly for 6 months, unsupervised: 2-3/week for the rest of the study duration); cognitive sessions (15-30 minutes/session, 3/week for 6 months, together with 10 workshops in 24 months). Vascular management takes place every 3-6 months or otherwise as specified by study physicians. The primary outcome is global cognition measured using the modified Neuropsychological Battery assessing performance in various domains, such as episodic memory, executive function and processing speed. Secondary outcome measures include: domain-specific cognition and function, imaging evidence of brain and retinal changes, incidence and progression of chronic diseases, blood biomarkers, quality of life, mental health and cost-benefit analysis., Conclusions: SINGER is part of the Worldwide-FINGERS international network, which is at the forefront of harmonizing approaches to effective non-pharmacological interventions in delaying cognitive decline in older adults at risk of dementia. By establishing the efficacy of multidomain interventions in preventing cognitive decline, SINGER aims to implement the findings into public health and clinical practices by informing policy makers, and guiding the design of community- and individual-level health promotion initiatives., Competing Interests: X. Xu has nothing to disclose. K. Chew has nothing to disclose. ZX. Wong has nothing to disclose. A. Phua has nothing to disclose. E. Chong has nothing to disclose. C. Teo has nothing to disclose. N. Sathe has nothing to disclose. YC. Chooi has nothing to disclose. W. Chia has nothing to disclose. C. Henry has nothing to disclose. E. Chew has nothing to disclose. MC. Wang has nothing to disclose. AB. Maier has nothing to disclose. N. Kandiah has nothing to disclose. C. Chen reports grants from the National University of Singapore and National Medical Research Council.

Although brain-computer interface (BCI) shows promising prospects to help post-stroke patients recover their motor function, its decoding accuracy is still highly dependent on feature extraction methods. Most current feature extractors in BCI are classification-based methods, yet very few works from literature use metric learning based methods to learn representations for BCI. To circumvent this shortage, we propose a deep metric learning based method, Weighted Convolutional Siamese Network (WCSN) to learn representations from electroencephalogram (EEG) signal. This approach can enhance the decoding accuracy by learning a low dimensional embedding to extract distance-based representations from pair-wise EEG data. To enhance training efficiency and algorithm performance, a temporal-spectral distance weighted sampling method is proposed to select more informative input samples. In addition, an adaptive training strategy is adopted to address the session-to-session non-stationarity by progressively updating the subject-specific model. The proposed method is applied on both upper limb and lower limb neurorehabilitation datasets acquired from 33 stroke patients, with a total of 358 sessions. Results indicate that using k-Nearest Neighbor as the classification algorithm, the proposed method yielded 72.8% and 66.0% accuracies for the two datasets respectively, significantly better than the other state-of-the-arts ( ). Without losing generality, we also evaluated the proposed method on two publicly available datasets acquired from healthy subjects, wherein the proposed algorithm demonstrated superior performance at most cases as well. Our results support, for the first time, the use of a metric learning based feature extractor to learn representations from non-stationary EEG signals for BCI-assisted post-stroke rehabilitation.

Objective: To assess the interchangeability of the Health Assessment Questionnaire disability index (HAQ DI) with the Patient-Reported Outcomes Measurement Information System-Physical Function (PROMIS-PF) in the calculation of minimal disease activity (MDA) in psoriatic arthritis (PsA)., Methods: Comprehensive PsA disease activity was collected concomitantly with the HAQ DI and the PROMIS-PF measures in a PsA cohort. The PROMIS-PF-based MDA definitions were built using the existing cross-walk between the scores: HAQ DI ≤0.5 equivalent to a PROMIS-PF T score of ≥41.3. We assessed agreement between MDA (MDA HAQ DI) and the PROMIS-PF MDA definitions (MDA PROMIS-PF short form 4a and MDA PROMIS-PF bank) at each visit and longitudinally (MDA state changes between consecutive visits) through the kappa statistic. The predictive value of the MDA PROMIS-PF for the MDA HAQ DI was assessed using receiver operator characteristic (ROC) curve analysis., Results: A total of 100 participants contributed 352 observations with up to 5 visits. The mean ± SD age was 52 ± 12 years, 60% were female, and 43% were in MDA at baseline. The kappa statistic for the PROMIS-PF-based MDA reflected excellent agreement with the HAQ DI MDA: κ = 0.94 (95% confidence interval [95% CI] 0.90-0.97) for MDA PROMIS-PF bank, and κ = 0.90 (95% CI 0.80-0.95) for MDA PROMIS-PF4a. Higher longitudinal agreement was seen between the MDA HAQ DI and the MDA PROMIS-PF bank versus the MDA PROMIS-PF4a between consecutive visits: κ values ranged between 0.81 and 0.94 versus a range between 0.72 and 0.84, respectively. The area under the ROC curve for predicting the MDA HAQ DI was 0.97 for the MDA PROMIS-PF bank and 0.95 for the MDA PROMIS-PF4a., Conclusion: Excellent agreement was seen between the HAQ DI and the PROMIS-based MDA definitions both cross-sectionally and longitudinally. The PROMIS-PF bank and PROMIS-PF4a are accurate replacements for the HAQ DI in calculating MDA state in PsA., (© 2021, American College of Rheumatology.)

Chronic inflammation promotes the development and progression of atherosclerosis. Despite aggressive risk reduction, patients with coronary artery disease have a significant residual risk of myocardial infarction and cardiovascular death related in part to ongoing inflammation within coronary vasculature. In this review, we summarize the clinical trials that provide evidence for the inflammatory hypothesis of atherogenesis. Additionally, we describe studies suggesting colchicine may be able to reduce residual inflammatory risk via the NLRP3 pathway. Given its tolerable side effect profile, safety, and low cost, colchicine holds promise as an anti-inflammatory agent in primary and secondary prevention of coronary disease., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Authors.)

At present, industrial robotics focuses more on motion control and vision, whereas humanoid service robotics (HSRs) are increasingly being investigated and researched in the field of speech interaction. The problem and quality of human-robot interaction (HRI) has become a widely debated topic in academia. Especially when HSRs are applied in the hospitality industry, some researchers believe that the current HRI model is not well adapted to the complex social environment. HSRs generally lack the ability to accurately recognize human intentions and understand social scenarios. This study proposes a novel interactive framework suitable for HSRs. The proposed framework is grounded on the novel integration of Trevarthen's (2001) companionship theory and neural image captioning (NIC) generation algorithm. By integrating image-to-natural interactivity generation and communicating with the environment to better interact with the stakeholder, thereby changing from interaction to a bionic-companionship. Compared to previous research a novel interactive system is developed based on the bionic-companionship framework. The humanoid service robot was integrated with the system to conduct preliminary tests. The results show that the interactive system based on the bionic-companionship framework can help the service humanoid robot to effectively respond to changes in the interactive environment, for example give different responses to the same character in different scenes., Competing Interests: Esyin Chew & Pengcheng Liu are Academic Editors for PeerJ., (© 2021 Yang et al.)

Two studies investigated the impact of recall timing on eyewitness memory. In Study 1, participants viewed a crime video and then completed the Self-Administered Interview (SAI © ) either immediately, after a 24-h delay, after a 1-week delay, or not at all. All participants completed a final recall questionnaire 2 weeks after they had viewed the stimulus video. Study 2 aimed to determine how long the beneficial impact of the SAI © on witnesses' long-term memory lasts. Participants watched a crime video and then either completed the SAI © or did not engage in an immediate recall attempt. Participants then completed a final recall questionnaire after a delay of 24 h, 1 week, 2 weeks, or 1 month. The results indicated that initial recall should be completed within 24 h of an incident and that under these conditions, the beneficial impact of early recall on long-term memory endures for at least 1 month., (© 2021 The Australian and New Zealand Association of Psychiatry, Psychology and Law.)

Brain-computer interface-assisted motor imagery (MI-BCI) or transcranial direct current stimulation (tDCS) has been proven effective in post-stroke motor function enhancement, yet whether the combination of MI-BCI and tDCS may further benefit the rehabilitation of motor functions remains unknown. This study investigated brain functional activity and connectivity changes after a 2 week MI-BCI and tDCS combined intervention in 19 chronic subcortical stroke patients. Patients were randomized into MI-BCI with tDCS group and MI-BCI only group who underwent 10 sessions of 20 min real or sham tDCS followed by 1 h MI-BCI training with robotic feedback. We derived amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo), and functional connectivity (FC) from resting-state functional magnetic resonance imaging (fMRI) data pre- and post-intervention. At baseline, stroke patients had lower ALFF in the ipsilesional somatomotor network (SMN), lower ReHo in the contralesional insula, and higher ALFF/Reho in the bilateral posterior default mode network (DMN) compared to age-matched healthy controls. After the intervention, the MI-BCI only group showed increased ALFF in contralesional SMN and decreased ALFF/Reho in the posterior DMN. In contrast, no post-intervention changes were detected in the MI-BCI + tDCS group. Furthermore, higher increases in ALFF/ReHo/FC measures were related to better motor function recovery (measured by the Fugl-Meyer Assessment scores) in the MI-BCI group while the opposite association was detected in the MI-BCI + tDCS group. Taken together, our findings suggest that brain functional re-normalization and network-specific compensation were found in the MI-BCI only group but not in the MI-BCI + tDCS group although both groups gained significant motor function improvement post-intervention with no group difference. MI-BCI and tDCS may exert differential or even opposing impact on brain functional reorganization during post-stroke motor rehabilitation; therefore, the integration of the two strategies requires further refinement to improve efficacy and effectiveness., 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., (Copyright © 2021 Hu, Cheng, Ji, Chong, Lu, Huang, Ang, Phua, Chuang, Jiang, Chew, Guan and Zhou.)

Selective targeting of BCL-2 with the BH3-mimetic venetoclax has been a transformative treatment for patients with various leukemias. TP-53 controls apoptosis upstream of where BCL-2 and its prosurvival relatives, such as MCL-1, act. Therefore, targeting these prosurvival proteins could trigger apoptosis across diverse blood cancers, irrespective of TP53 mutation status. Indeed, targeting BCL-2 has produced clinically relevant responses in blood cancers with aberrant TP-53. However, in our study, TP53-mutated or -deficient myeloid and lymphoid leukemias outcompeted isogenic controls with intact TP-53, unless sufficient concentrations of BH3-mimetics targeting BCL-2 or MCL-1 were applied. Strikingly, tumor cells with TP-53 dysfunction escaped and thrived over time if inhibition of BCL-2 or MCL-1 was sublethal, in part because of an increased threshold for BAX/BAK activation in these cells. Our study revealed the key role of TP-53 in shaping long-term responses to BH3-mimetic drugs and reconciled the disparate pattern of initial clinical response to venetoclax, followed by subsequent treatment failure among patients with TP53-mutant chronic lymphocytic leukemia or acute myeloid leukemia. In contrast to BH3-mimetics targeting just BCL-2 or MCL-1 at doses that are individually sublethal, a combined BH3-mimetic approach targeting both prosurvival proteins enhanced lethality and durably suppressed the leukemia burden, regardless of TP53 mutation status. Our findings highlight the importance of using sufficiently lethal treatment strategies to maximize outcomes of patients with TP53-mutant disease. In addition, our findings caution against use of sublethal BH3-mimetic drug regimens that may enhance the risk of disease progression driven by emergent TP53-mutant clones., (© 2021 by The American Society of Hematology.)

Introduction: The aim of this research was to evaluate the impact of a novel tele-rehabilitation system on self-reported functional outcomes compared to usual care during the first three months after stroke., Methods: A parallel, two-arm, evaluator-blinded, randomised controlled trial was conducted. Adults aged ≥40 years who had suffered a stroke within four weeks of the start of the study were recruited from the general community. The intervention group received access to a novel tele-rehabilitation system and programme for three months. The primary outcome measures utilised were the frequency and limitation total scores of the Late-Life Function and Disability Instrument (LLFDI) at three months., Results: A total of 124 individuals were recruited. The mean differences in the LLDFI frequency and limitation total scores at three months comparing the intervention and control groups were -3.30 (95% confidence interval (CI) -7.81 to 1.21) and -6.90 (95% CI -15.02 to 1.22), respectively. Adjusting for the respective baseline covariates and baseline Barthel Index also showed no significant difference between interventions in the LLFDI outcomes., Discussion: The intervention and control groups self-reported similar improvements in functional outcomes. Tele-rehabilitation may be a viable option to provide post-stroke rehabilitation services in Singapore while reducing barriers to continue rehabilitation conventionally after discharge from hospital and encouraging more participation.