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Kaida Jiang,1 Lingjiang Li,2 Xueyi Wang,3 Maosheng Fang,4 Jianfei Shi,5 Qiuyun Cao,6 Jincai He,7 Jinan Wang,8 Weihao Tan,8 Cuili Hu8 1Psychiatry Department, Shanghai Mental Health Center, Shanghai, 2Psychiatry Department,The Second Xiangya Hospital, Central South University, Changsha, 3Psychiatry Department, First affiliated Hospital of Hebei Medical University, Shijiazhuang, 4Psychiatry Department, Wuhan Mental Health Center, Wuhan, 5Psychiatry Department, Hangzhou the 7th Hospital, Hangzhou, 6Psychology Department, Nanjing Drum Tower Hospital, Nanjing, 7Neurology Department, First affiliated Hospital of Wenzhou Medical University, Wenzhou, 8Medical Affairs Department, Xi’an Janssen Pharmaceutical Ltd., Beijing, People’s Republic of China Background: Significant anxiety symptoms are associated with poor clinical course and outcome in major depressive disorder (MDD). This single-arm, open-label study aimed to evaluate the efficacy and tolerability of escitalopram treatment in patients with MDD and anxiety symptoms. Methods: Adult patients with MDD and anxiety symptoms (Montgomery–Asberg Depression Rating Scale [MADRS] ≥22 and Hamilton Anxiety Rating Scale [HAM-A] ≥14) were enrolled and received escitalopram (10–20 mg/day) treatment for 24 weeks. Symptom status was assessed by MADRS, 17-item-Hamilton Depression Rating Scale, HAM-A, and Clinical Global Impression Scale at baseline and the following visits. Quality of life was assessed by Short Form-12, and safety was evaluated by adverse events, laboratory investigations, vital signs, and physical findings. Results: Overall, 200 of 318 (66.2%) enrolled patients completed the 24-week treatment. The remission (MADRS ≤10 and HAM-A ≤7) rate in the full analysis set (N=285) was 73.3% (95% confidence interval: 67.80, 78.38) at week 24. Mean (± standard deviation) MADRS total score was 33.4 (±7.13) and HAM-A score was 27.6 (±7.26) at baseline, which reduced to 6.6 (±10.18) and 6.0 (±8.39), respectively, at week 24. Patients with higher baseline depression and anxiety level took longer to achieve similar remission rates. Overall, 80 of the 302 (26.5%) patients included in the safety set reported at least 1 treatment-emergent adverse event (TEAE). Most frequently reported TEAEs (>2%) were headache (4.0%), nasopharyngitis (3.6%), nausea (3.0%), and dizziness (2.6%). Serious TEAEs were reported by 1.3% patients; no deaths were reported. Conclusion: Escitalopram 10–20 mg/day was effective and well-tolerated in the long-term treatment of MDD with anxiety symptoms in adult Chinese population. Keywords: anxiety, Chinese, escitalopram, long term, major depressive disorder

BackgroundAngelman syndrome (AS) is a neurodevelopmental disorder caused by a lack of expression of the maternally inherited UBE3A gene on chromosome 15. Individuals with AS due to a UBE3A mutation are more likely to have siblings who also have AS compared with those with AS due to other cytogenetic/molecular mechanisms, but it is unknown whether the developmental outcome of siblings who have AS is similar.MethodsThrough an ongoing AS Natural History Study, we identified seven pairs of siblings with AS due to a UBE3A mutation. We compared the neurodevelopment of the first-born and second-born siblings with AS participants who have a UBE3A mutation and have either typically developing siblings or no siblings.ResultsSecond-born AS participants due to a UBE3A mutation were more likely to be diagnosed at an earlier age. With the exception of higher expressive language scores among the second-born participants, no other differences were observed in the developmental and adaptive functioning skills across the different groups.ConclusionsThe presence of an older sibling with the same neurodevelopmental disorder is associated with an earlier age of diagnosis and may be associated with an improvement in expressive language skills; the developmental outcome of siblings with AS due to a UBE3A mutation is otherwise comparable.

This study aimed to explore the isomer-specific, sex-specific, and joint associations of PFAS and red blood cell indices. We used data of 1,238 adults from the Isomers of C8 Health Project in China. Associations of PFAS isomers and red blood cell indices were explored using multiple linear regression models, Bayesian Kernel Machine Regression models and subgroup analysis across sex. We found that serum concentration of linear (n-) and branched (Br-) isomers of perfluorooctane sulfonate (PFOS) and perfluorohexanesulfonic acid (PFHxS) were significantly associated with red blood cell indices in single-pollutant models, with stronger associations observed for n-PFHxS than Br-PFHxS, in women than in men. For instance, the estimated percentage change in hemoglobin concentration for n-PFHxS (3.65%; 95% CI: 2.95%, 4.34%) was larger than that for Br-PFHxS (0.96%; 95% CI: 0.52%, 1.40%). The estimated percentage change in red blood cell count for n-PFHxS in women (2.55%; 95% CI: 1.81%, 3.28%) was significantly higher than that in men (0.12%; 95% CI: -1.04%, 1.29%) ( P inter < 0.001). Similarly, sex-specific positive association of PFAS mixture and outcomes was observed. Therefore, the structure, susceptive population, and joint effect of PFAS isomers should be taken into consideration when evaluating the health risk of chemicals.

Background: Residency programs are required to incorporate simulation into their training program. Ideally, simulation provides a safe environment for a trainee to be exposed to both common and challenging clinical scenarios. The purpose of this review is to detail the current state of the most commonly used laparoscopic, endoscopic, and robotic surgery simulation programs in general surgery residency education, including resources required for successful implementation and benchmarks for evaluation., Materials and Methods: Members of the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) Resident and Fellow Task Force (RAFT) Committee performed a literature review using PubMed and training websites. Information regarding the components of the most commonly used laparoscopic, endoscopic, and/or robotic simulation curriculum, including both formal and informal benchmarks for evaluating training competence, were collected., Results: Laparoscopic simulation revolves around the Fundamentals of Laparoscopic Surgery (FLS). Proficiency-based as well as virtual simulation have been utilized for FLS training curricula. Challenges include less direct translation to the technical complexities that can arise in laparoscopic surgery. Endoscopic simulation focuses on the Fundamentals of Endoscopic Surgery. There are virtual reality simulation platforms that can be used for skills assessment and training. Challenges include simulator types and access, as well as structured mentoring and feedback. Robotic simulation training curricula have not been standardized. Simulation includes one primary technology, which can be prohibitive based on cost and requirements for onboarding., Conclusions: While surgical simulation seems to be a fundamental and integrated part of surgical training, it requires a significant number of resources, which can be daunting for residency training programs. Regardless of the barriers outlined, the need for surgical simulation in laparoscopy, endoscopy, and robotics at surgical education training programs is clear., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Little is known about the prevalence of dermatoses in "skin-well" geriatric Singaporeans. We aim to identify the prevalence of dermatoses and their associations within the geriatric population in Singapore, and to understand the distribution of dermatological encounters presenting to primary care physicians, and the resultant referral behaviour., Methods: A joint quantitative-qualitative study was performed across 8 months. Patients aged 65 years and above who visited a local polyclinic for management of non-dermatological chronic diseases were recruited. They were administered questionnaires, and underwent full skin examinations. Online surveys were disseminated to polyclinic physicians under the same healthcare cluster., Results: 201 patients and 53 physicians were recruited. The most common dermatoses identified in patients were benign tumours and cysts (97.5%), and asteatosis (81.6%). For every 1-year increase in age, the odds of having asteatosis increased by 13.5% (95% CI 3.4-24.7%, p = 0.008), and urticarial disorders by 14.6% (95% CI 0.3-30.9%, p = 0.045). Patients who used any form of topical preparations on a daily basis had higher odds of having eczema and inflammatory dermatoses (OR 2.51, 95% CI 1.38 to 4.56, p = 0.003). Physicians reported dermatological conditions involving 20% of all clinical encounters. Eczema represented the most commonly reported dermatosis within the first visit. 50% of dermatology referrals were done solely at the patient's own request., Conclusion: The prevalence of dermatoses in the elderly in Singapore is high, especially asteatosis. Prompt recognition by the primary healthcare provider potentially prevents future morbidity. Outreach education for both primary care physicians and the general public will be key., Ethics Approval: National Healthcare group (NHG) Domain Specific Review Board (DSRB), Singapore, under Trial Registration Number 2020/00239, dated 11 August 2020., (© 2024. The Author(s).)

Rapid growth has been witnessed in digital technologies, resulting in significant productive changes in communication and information technology-oriented practices in different fields. Hybrid teaching or blended learning has gained progressively widespread acceptance in the educational process, and concerns about teachers' information and communication technology (ICT) competence or digital competence have become prevalent. This study adopts a systematic review to interpret and analyse the relevant research findings, aiming to systematically investigate the existing models and paradigms of ICT competence or digital capacities and to understand further how these models and paradigms are applied specifically within the context of Chinese universities. Based on inclusion and exclusion criteria, 12 out of 801 candidate studies were accessed from Web of Science, Scopus and the China National Knowledge Infrastructure (CNKI) databases. The findings indicate that the Technological Pedagogical Content Knowledge (TPACK) and the National Educational Technology Guides for Teachers in Higher Education (CETG) are frequently used to evaluate college educators' digital proficiency or ICT capability in China. Educators' demographic characteristics, self-efficacy, external factors such as institutional policies and the availability of infrastructure and training collectively influence how digital teaching is integrated within Chinese higher education institutions. By conducting a systematic review of research trends and the critical factors affecting the digital competence of faculty in Chinese universities, this study aims to equip policymakers and educators with a deeper understanding of how to prepare for educational shifts in the digital era and thereby ensure the sustainability of professional development., 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 Ltd.)

Objective: The purpose of this study is to investigate predictors of pressure injury (PrI) outcomes at one year after discharge for Veterans with spinal cord injury (SCI) hospitalized with a Stage 3 or 4 PrI., Design/setting/participants: This is a retrospective medical record review from one VA Health Care System SCI unit. Participants were Veterans with traumatic or non-traumatic SCI admitted with one Stage 3 or 4 pelvic PrI treated medically (e.g. without flap surgery). Logistic models were used to select the significant predictors of PrI healing outcomes., Outcome Measure: One year after discharge wound outcomes (healed vs non-healed) for Veterans with SCI hospitalized with a Stage 3 or 4 PrI., Results: A total of 62 hospitalizations were included for analyses resulting in 33 healed and 29 non-healed PrIs. Three significant predictors of non-healed PrI outcomes included use of pressure mapping during hospitalization, greater PrI depth, and usage of alginate dressings. Two significant predictors of healed PrI outcomes included the use of animal-based tissue and hydrocolloid dressings. Area under curve of this logistic regression model was 79.98%., Conclusion: The clinical decision of having a patient pressure mapped predicts that the PrI may not heal at one year of discharge. Pressure mapping protocol correlated with another variable that could not serve as a predictor by itself, including using powered pressure relief techniques. The three PrI treatment predictors may represent characteristics of the PrI itself, rather than the efficacy of the product. Further investigation on these clinical decision-making factors is warranted to ensure efficient and cost-effective treatment strategies for individuals with SCI hospitalized with PrIs.

Background: Angelman syndrome (AS) is a neurodevelopmental disorder associated with severe global developmental delay. However, the ages at which different developmental skills are achieved in these individuals remain unclear. We seek to determine the probability and the age of acquisition of specific developmental milestones and daily living skills in individuals with AS across the different molecular subtypes, viz. class I deletion, class II deletion, uniparental disomy, imprinting defect, and UBE3A variants., Methods: Caregivers participating in a longitudinal multicenter Angelman Syndrome Natural History Study completed a questionnaire regarding the age at which their children achieved specific developmental milestones and daily living skills. The Cox Proportional Hazard model was applied to analyze differences in the probability of achievement of skills at various ages among five molecular subtypes of AS., Results: Almost all individuals, regardless of molecular subtype, were able to walk with support by five years of age. By age 15, those with a deletion had at least a 50% probability of acquiring 17 out of 30 skills compared to 25 out of 30 skills among those without a deletion. Overall, fine and gross motor skills such as holding and reaching for small objects, sitting, and walking with support were achieved within a fairly narrow range of ages, while toileting, feeding, and hygiene skills tend to have greater variability in the ages at which these skills were achieved. Those without a deletion had a higher probability (25-92%) of achieving daily living skills such as independently toileting and dressing compared to those with a deletion (0-13%). Across all molecular subtypes, there was a low probability of achieving independence in bathing and brushing teeth., Conclusion: Individuals with AS without a deletion are more likely to achieve developmental milestones and daily living skills at an earlier age than those with a deletion. Many individuals with AS are unable to achieve daily living skills necessary for independent self-care., (© 2024. The Author(s).)

The panoramic stereo video has brought a new visual experience for the audience with its immersion and stereo effect. In panoramic stereo video, the face is an important element. However, the face image in panoramic stereo video has varying degrees of deformation. This brings new challenges to face recognition. Therefore, this paper proposes a face recognition model DCM2Net (Deformable Convolution MobileFaceNet) for panoramic stereo video. The model mainly integrates the feature information between channels during feature fusion, redistributes the information between channels in the deeper part of the network, and fully uses the information between different channels for feature extraction. This paper also built a panoramic stereo video live system, using the DCM2Net model to recognize the face in panoramic stereo video, and the recognition results are displayed in the video. After experiments on different datasets, the results show that our model has better results on popular datasets and panoramic datasets., 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 Zhang, Tan, Wei and Tan.)

Objectives: To evaluate asthma characteristics and treatment patterns, including short-acting β 2 -agonist (SABA) prescriptions, in primary and specialist care in the Singapore cohort of the SABA use IN Asthma (SABINA III) study., Design: Cross-sectional, observational study., Setting: Multicentre study conducted at five sites across Singapore., Methods: In patients with asthma (aged ≥12 years), data on demographics, disease characteristics and asthma treatment prescriptions were collected using electronic case report forms. Patients were classified by investigator-defined asthma severity (guided by 2017 Global Initiative for Asthma recommendations) and practice type (primary/specialist care)., Results: Of the 205 patients analysed (mean (SD) age, 53.6 (16.8) years; female, 62%), 55.9% were enrolled by specialists and 44.1% by primary care physicians. Most study patients (80.5%) had moderate-to-severe asthma (86.0% in specialist care and 74.4% in primary care). In the 12 months before study enrolment, 18.0% of patients experienced ≥1 severe exacerbation. Asthma was well or partly controlled in 78.0% of patients. Overall, 17.1% of all patients were overprescribed SABA (≥3 SABA canisters/year) in the preceding 12 months, and overprescription was greater in specialist versus primary care (26.3% vs 5.6%). Only 2.9% of patients were prescribed SABA monotherapy, while 41.0% received SABA in addition to maintenance therapy. Among the latter, 40.5% were overprescribed SABA. Overall, a higher percentage of patients prescribed ≥3 SABA canisters (vs 0-2 SABA canisters) were assessed as having uncontrolled asthma during the study visit (42.9% vs 17.6%). Maintenance therapy in the form of inhaled corticosteroids (ICS) or ICS/long-acting β 2 agonist fixed-dose combinations were prescribed to 14.1% and 84.9% of patients, respectively, in the 12 months before enrolment., Conclusions: In this Singapore cohort, ~17% of all patients and more than 40% of patients prescribed SABA in addition to maintenance therapy were overprescribed SABA. These findings emphasise the need to align clinical practices with the latest evidence-based treatment recommendations., Trial Registration: NCT03857178., Competing Interests: Competing interests: DHYT has received honorarium from AstraZeneca as well as consultation fees from GSK in the past. TLT has received honorarium from AstraZeneca in the past. CC was an employee of AstraZeneca at the time of manuscript development. MJHIB was an employee of AstraZeneca at the time of the study conduct. WHT, JHK, SSK, GRW and HFL have no conflicts of interest to declare., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Most vertebrates develop distinct females and males, where sex is determined by repeatedly evolved environmental or genetic triggers. Undifferentiated sex chromosomes and large genomes have caused major knowledge gaps in amphibians. Only a single master sex-determining gene, the dmrt1-paralogue (dm-w) of female-heterogametic clawed frogs (Xenopus; ZW♀/ZZ♂), is known across >8740 species of amphibians. In this study, by combining chromosome-scale female and male genomes of a non-model amphibian, the European green toad, Bufo(tes) viridis, with ddRAD- and whole genome pool-sequencing, we reveal a candidate master locus, governing a male-heterogametic system (XX♀/XY♂). Targeted sequencing across multiple taxa uncovered structural X/Y-variation in the 5'-regulatory region of the gene bod1l, where a Y-specific non-coding RNA (ncRNA-Y), only expressed in males, suggests that this locus initiates sex-specific differentiation. Developmental transcriptomes and RNA in-situ hybridization show timely and spatially relevant sex-specific ncRNA-Y and bod1l-gene expression in primordial gonads. This coincided with differential H3K4me-methylation in pre-granulosa/pre-Sertoli cells, pointing to a specific mechanism of amphibian sex determination., (© 2024. The Author(s).)

The aim of this study was to investigate the in-use compatibility of eight commercially available closed system transfer device brands (CSTDs) with a formulated model antibody drug conjugate (ADC). Overall, in-use simulated dosing preparation applying the CSTD systems investigated raised concerns for several product quality attributes. The incompatibilities observed were mainly associated with increased visible and subvisible particles formation as well as significant changes in holdup volumes. Visible and subvisible particles contained heterogeneous mixtures of particle classes, with the majority of subvisible particles associated with silicone oil leaching from CSTD systems during simulated dose preparation upon contact with the ADC formulation. These observations demonstrate that CSTD use may adversely impact product quality and delivered dose which could potentially lead to safety and efficacy concerns during administration. Other product quality attributes measured including turbidity, color, ADC recovery, and purity by size exclusion HPLC, did not show relevant changes. It is therefore strongly recommended to test and screen the compatibility of CSTDs with the respective ADC, in a representative in-use simulated administration setting, during early CMC development, i.e., well before the start of clinical studies, to include information about compatibility and to ensure that the CSTD listed in the manuals of preparation for clinical handling has been thoroughly assessed before human use., (© 2024. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

Background: Pressure injuries (PI) are a significant source of morbidity for individuals with spinal cord injury/disease (SCI/D). They are also associated with significant healthcare resource utilization including prolonged hospitalizations. However, the long-term outcomes in terms of wound recurrence-free survival, hospital readmission rates, and all-cause mortality in this population remain largely unknown., Objective: To examine the clinical characteristics, healthcare utilization and outcomes of SCI Veterans hospitalized at the VA North Texas Health Care System (VANTHCS) SCI inpatient unit with stage 3 and 4 PI, and compare these between those who received a myocutaneous flap surgery (flap patients (FP)) and those treated medically (non-flap patients (NFP))., Methods: A retrospective chart review was conducted of all adult patients admitted to the VANTHCS SCI/D unit with stage 3 or 4 pelvic PI between 1/1/2013 and 12/31/2018. Healthcare utilization and outcome information was extracted for pre-specified time points., Results: 78 patients met criteria (113 hospitalizations; 27 FP; 51 NFP). Average length of stay (LOS) was 122 days; FP had a significantly higher LOS than NFP (P = 0.01). Average number of consults was 24. Estimated cost per hospitalization was $175,198. Readmission rate within 30 days was 12.39%. The mortality rate within 1 year of discharge was 21.57% for NFP, as opposed to 3.70% in the FP group. Only 5.00% of NFP wounds were healed at discharged with sustained healing at 1 year, significantly less than FP wounds (55.26%, P < 0.01)., Conclusions: Despite the high investment in terms of healthcare utilization, outcomes in terms of wound healing are poor. Additionally, nearly 22% of NFP died within one year of discharge. This calls into question the utility of prolonged hospitalizations for PI in the SCI/D population in terms of wound treatment efficacy, healthcare costs, and patient morbidity/mortality.

Curcuma aromatica Salisb (Cur), a well-known herbal medicine, has a wide spectrum of anti-inflammatory, anticarcinogenic, and antioxidant activities. However, the roles of its active compounds and potential mechanisms in colorectal cancer remain unknown. This research utilized network pharmacology and experimental validation to explore the possible mechanisms by which Cur protects against colorectal cancer. The active compounds of Cur and related genes for colorectal cancer were obtained from public databases. The DrugBank database was used to search for anticolorectal cancer drugs licensed through the FDA and their targets, and a "drug-component-target" relationship network was created using the Cytoscape program. The String database produced the PPI network. The ability of these active ingredients to bind to core targets was confirmed by molecular docking using AutoDock Vina. Cell and animal experiments were then carried out. A total of 274 targets were obtained from Cur, 49 of which were potential therapeutic targets. Four key targets, PTGS2, AKT1, TP53, and estrogen receptor 1 (ESR1), were screened via the PPI network and the FDA drug-target network. Molecular docking results revealed that Cur had strong binding abilities to these targets. In vivo and in vitro experiments demonstrated that Cur suppressed the development of colorectal cancer by regulating its targets (PTGS2, AKT1, TP53, and ESR1), which play crucial roles in promoting apoptosis and suppressing cell proliferation, migration, and invasion. Collectively, Cur protects against colorectal cancer by regulating the AKT1/PTGS2/ESR1 and P53 pathways, which lays the groundwork for further research and clinical applications of Cur in colorectal cancer therapy., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Background: Although the indoor environment has been proposed to be associated with childhood sleep health, to our knowledge no study has investigated the association between home renovation and childhood sleep problems., Methods: The study included 186,470 children aged 6-18 years from the National Chinese Children Health Study (2012-2018). We measured childhood sleeping problems via the Chinese version of the Sleep Disturbance Scale for Children (C-SDSC). Information on home renovation exposure within the recent 2 years was collected via parent report. We estimated associations between home renovation and various sleeping problems, defined using both continuous and categorized (binary) C-SDSC t-scores, using generalized mixed models. We fitted models with city as a random effect variable, and other covariates as fixed effects., Results: Out of the overall participants, 89,732 (48%) were exposed to recent home renovations. Compared to the unexposed group, children exposed to home renovations had higher odds of total sleep disorder (odd ratios [OR] = 1.3; 95% confidence interval [CI] = 1.2, 1.4). Associations varied when we considered different types of home renovation materials. Children exposed to multiple types of home renovation had higher odds of sleeping problems. We observed similar findings when considering continuous C-SDSC t-scores. Additionally, sex and age of children modified the associations of home renovation exposure with some of the sleeping problem subtypes., Conclusions: We found that home renovation was associated with higher odds of having sleeping problems and that they varied when considering the type of renovation, cumulative exposure, sex, and age differences., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Electroencephalogram (EEG) signals are critical in interpreting sensorimotor activities for predicting body movements. However, their efficacy in identifying intralimb movements, such as the dorsiflexion and plantar flexion of the foot, remains suboptimal. This study aims to explore whether various EEG signal quantities can effectively recognize intralimb movements to facilitate the development of Brain-Computer Interface (BCI) devices for foot rehabilitation. This research involved twenty-two healthy, right-handed participants. EEG data were collected using 21 electrodes positioned over the motor cortex, while two electromyography (EMG) electrodes recorded the onset of ankle joint movements. The study focused on analyzing slow cortical potential (SCP) and sensorimotor rhythms (SMR) in alpha and beta bands from the EEG. Five key features-fourth-order Autoregressive feature, variance, waveform length, standard deviation, and permutation entropy-were extracted. A modified Recurrent Neural Network (RNN) including Long Short-term Memory (LSTM) and Gated Recurrent Unit (GRU) algorithms was developed for movement recognition. These were compared against conventional machine learning algorithms, including nonlinear Support Vector Machine (SVM) and k Nearest Neighbourhood (kNN) classifiers. The performance of the proposed models was assessed using two data schemes: within-subject and across-subjects. The findings demonstrated that the GRU and LSTM models significantly outperformed traditional machine learning algorithms in recognizing different EEG signal quantities for intralimb movement. The study indicates that deep learning models, particularly GRU and LSTM, hold superior potential over standard machine learning techniques in identifying intralimb movements using EEG signals. Where the accuracies of LSTM for within and across subjects were 98.87 ± 1.80 % and 87.38 ± 0.86 % respectively. Whereas the accuracy of GRU within and across subjects were 99.18 ± 1.28 % and 86.44 ± 0.69 % respectively. This advancement could significantly benefit the development of BCI devices aimed at foot rehabilitation, suggesting a new avenue for enhancing physical therapy outcomes., 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.)

Background: Personalised care and support planning (CSP) is a person-centred approach for the care of people living with long-term conditions. Patient Activation through Community Empowerment/Engagement for Diabetes Management (PACE-D) adapts the Year of Care Partnerships (YOCP) approach to CSP in the UK for people living with diabetes at Singapore polyclinics. Polyclinics are multi-storey primary care hubs that provide affordable, multidisciplinary, comprehensive, and high-throughput public health care for the multi-ethnic, multilingual Singapore population., Aim: To explore the experience of PACE-D-enrolled people living with diabetes with personalised CSP at Singapore polyclinics., Design & Setting: Qualitative interviews of people living with diabetes who experienced personalised CSP at National University Polyclinics (NUP) in Singapore between July 2020 and November 2021., Method: PACE-D-enrolled people living with diabetes who experienced personalised CSP were purposively sampled. In-depth semi-structured interviews were recorded, transcribed, and analysed using Braun and Clarke's reflexive thematic analysis., Results: Fifty-two patients participated in the study. Four main themes were identified. Theme 1 was the importance of the care-planning letter. Patients reported that the CPL prompted reflection and patient preparation for CSP conversations. Theme 2 was the role of the programme coordinator. PACE-D programme coordinators amplified self-management by playing advocate and confidant beyond administrative duties. Theme 3 was the value of the personalised CSP conversation. CSP providers were perceived as partners in care, with more time to listen compared with usual consultations. Patient engagement was affected by language confidence. Theme 4 was agency in self-management. With adequate time and support, patients increased in confidence and agency both in CSP engagement and diabetes self-management., Conclusion: While language confidence may affect patient engagement, personalised CSP shows promise for strengthening patient engagement and self-management among people living with diabetes at Singapore polyclinics., (Copyright © 2024, The Authors.)

The emissions and exposure limits for airborne PM 0.1 are lacking, with limited scientific data for toxicity. Therefore, we continuously monitored and calculated the number and mass concentrations of airborne PM 0.1 in December 2017, January 2018 and March 2018 during the high pollution period in Guangzhou. We collected PM 0.1 from the same period and analyzed their chemical components. A549, THP-1 and A549/THP-1 co-cultured cells were selected for exposure to PM 0.1 , and evaluated for toxicological responses. Our aims are to 1) measure and analyze the number and mass concentrations, and chemical components of PM 0.1 ; 2) evaluate and compare PM 0.1 toxicity to different airway cells models at different time points. Guangzhou had the highest mass concentration of PM 0.1 in December 2017, while the number concentration was the lowest. Chemical components in PM 0.1 vary significantly at different time periods, and the correlation between the chemical composition or source of PM 0.1 and the mass and number concentration of PM 0.1 was dissimilar. Exposure to PM 0.1 disrupted cell membranes, impaired mitochondrial function, promoted the expression of inflammatory mediators, and interfered with DNA replication in the cell cycle. The damage caused by exposure to PM 0.1 at different times exhibited variations across different types of cells. PM 0.1 in March 2018 stimulated co-cultured cells to secrete more inflammatory mediators, and CMA was significantly related to the expression of them. Our study indicates that it is essential to monitor both the mass and number concentrations of PM 0.1 throughout all seasons annually, as conventional toxicological experiments and the internal components of PM 0.1 may not effectively reveal the health damages caused by elevated number levels of PM 0.1 ., 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 © 2024. Published by Elsevier B.V.)

Background: The genus Clavicornaltica Scherer 1974 consists of very small, soil-dwelling flea beetles in South, Southeast and East Asia. Due to their diminutive size and morphological similarities, very little is known about their ecology and taxonomical diversity. It is likely that further studies will reveal this genus to be much more speciose than the 30 species currently recognised., New Information: A new species of Clavicornaltica from Brunei Darussalam is described, C.mataikanensis Otani et al., sp. nov. This is the second species of this genus recorded from Ulu Temburong National Park., (Sean Otani, Luca Bertoli, Filippo Lucchini, Tom P. G. van den Beuken, Desanne Boin, Lehman Ellis, Holm Friedrich, Brittany Jacquot, Sotiris Kountouras, Sarah Yu Rou Lim, Eleonora Nigro, Syafi’ie Su’eif, Wei Harn Tan, Ulmar Grafe, Daniele Cicuzza, Massimo Delledonne, Iva Njunjić, Menno Schilthuizen.)

Heterozygous mutations in COL10A1 lead to metaphyseal chondrodysplasia type Schmid (MCDS), a skeletal disorder characterized by epiphyseal abnormalities. Prior analysis revealed impaired trimerization and intracellular retention of mutant collagen type X alpha 1 chains as cause for elevated endoplasmic reticulum (ER) stress. However, how ER stress translates into structural defects remained unclear. We generated a medaka ( Oryzias latipes ) MCDS model harboring a 5 base pair deletion in col10a1 , which led to a frameshift and disruption of 11 amino acids in the conserved trimerization domain. col10a1 Δ633a heterozygotes recapitulated key features of MCDS and revealed early cell polarity defects as cause for dysregulated matrix secretion and deformed skeletal structures. Carbamazepine, an ER stress-reducing drug, rescued this polarity impairment and alleviated skeletal defects in col10a1 Δ633a heterozygotes. Our data imply cell polarity dysregulation as a potential contributor to MCDS and suggest the col10a1 Δ633a medaka mutant as an attractive MCDS animal model for drug screening., Competing Interests: The authors declare no competing interests., (© 2024 The Author(s).)

Background: During the past decade, the proportion of bariatric surgery performed robotically has been rising. However, the clinical benefits of the robotic approach over laparoscopy are uncertain. One area in need of further investigation is pain control after robotic versus laparoscopic bariatric surgery., Methods: A retrospective cohort study was conducted of bariatric surgery patients undergoing laparoscopic or robotic sleeve gastrectomy at a single institution from October 2019 to August 2022. Inpatient opioid use was measured in morphine milliequivalents. Pain scores were collected by the nursing staff., Results: A total of 368 patients were included: 286 laparoscopic and 82 robotic surgery patients. The groups shared similar demographics. For the entire cohort, the mean age was 42 years, the body mass index was 50 kg/m 2 , and 79% were female. Mean operative time was significantly lower for laparoscopic surgeries (87.5 ± 47.3 minutes vs 109.3 ± 30.3 minutes; P < .01). The median total inpatient morphine milligram equivalents used was similar for both groups: 52.3 (31.5-77.0) for the laparoscopic group versus 40 (24-74.5) for robotic (P = .13). Mean postoperative pain scores (scale out of 10) were not significantly different between groups: 5.2 ± 1.7 (postoperative day 0) and 4.5 ± 1.7 (day 1) for laparoscopic patients versus 5.1 ± 2.0 (day 0) and 4.4 ± 1.8 (day 1) for robotic. The proportion of patients prescribed opioids at discharge was significantly higher for the laparoscopic group (75.2% vs 62.2%; P = .02). Other clinical outcomes, including duration of stay, 30-day readmissions, and visits to the emergency department, were not significantly different., Conclusion: There is no difference in inpatient opioid use or pain scores between patients undergoing laparoscopic and robotic sleeve gastrectomy., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Bariatric surgery is routinely performed using laparoscopic and robotic approaches. Musculoskeletal injuries are prevalent among both robotic and laparoscopic bariatric surgeons. Studies evaluating ergonomic differences between laparoscopic and robotic bariatric surgery are limited. This study aims to analyze the ergonomic, physical, and mental workload differences among surgeons performing robotic and laparoscopic bariatric surgery., Materials and Methods: All primary laparoscopic and robotic bariatric surgeries, Roux-en-Y gastric bypass, and sleeve gastrectomy between May and August 2022 were included in this study. Objective ergonomic analysis was performed by an observer evaluating each surgeon intraoperatively according to the validated Rapid Entire Body Assessment tool, with a higher score indicating more ergonomic strain. After each operation, surgeons subjectively evaluated their physical workload using the body part discomfort scale, and their mental workload using the surgery task load index., Results: Five bariatric surgeons participated in this study. In total, 50 operative cases were observed, 37 laparoscopic and 13 robotic. The median total Rapid Entire Body Assessmentscore as a primary surgeon was significantly higher in laparoscopic (6.0) compared to robotic (3.0) cases (P < 0.01). The laparoscopic and robotic approaches had no significant differences in the surgeons' physical (body part discomfort scale) or mental workload (surgery task load index)., Conclusions: This study identified low-risk ergonomic stress in surgeons performing bariatric surgery robotically compared to medium-risk stress laparoscopically. Since ergonomic stress can exist even without the perception of physical or mental stress, this highlights the importance of external observations to optimize ergonomics for surgeons in the operating room., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: Recurrent deletions involving 17q12 are associated with a variety of clinical phenotypes, including congenital abnormalities of the kidney and urinary tract (CAKUT), maturity onset diabetes of the young, type 5, and neurodevelopmental disorders. Structural and/or functional renal disease is the most common phenotypic feature, although the prenatal renal phenotypes and the postnatal correlates have not been well characterized., Method: We reviewed pre- and postnatal medical records of 26 cases with prenatally or postnatally identified 17q12/HNF1B microdeletions (by chromosomal microarray or targeted gene sequencing), obtained through a multicenter collaboration. We specifically evaluated 17 of these cases (65%) with reported prenatal renal ultrasound findings., Results: Heterogeneous prenatal renal phenotypes were noted, most commonly renal cysts (41%, n = 7/17) and echogenic kidneys (41%), although nonspecific dysplasia, enlarged kidneys, hydronephrosis, pelvic kidney with hydroureter, and lower urinary tract obstruction were also reported. Postnatally, most individuals developed renal cysts (73%, 11/15 live births), and there were no cases of end-stage renal disease during childhood or the follow-up period., Conclusion: Our findings demonstrate that copy number variant analysis to assess for 17q12 microdeletion should be considered for a variety of prenatally detected renal anomalies. It is important to distinguish 17q12 microdeletion from other etiologies of CAKUT as the prognosis for renal function and presence of associated findings are distinct and may influence pregnancy and postnatal management., (© 2023 John Wiley & Sons Ltd.)

Small teleost fishes such as zebrafish and medaka show remarkable regeneration capabilities upon tissue injury or amputation. To elucidate cellular mechanisms of teleost tissue repair and regeneration processes, the Cre/LoxP recombination system for cell lineage tracing is a widely used technique. In this chapter, we describe protocols used for inducible Cre/LoxP recombination-mediated lineage tracing of osteoblast progenitors during medaka fin regeneration as well as during the repair of osteoporosis-like bone lesions in the medaka vertebral column. Our approach can be adapted for lineage tracing of other cell populations in the regenerating teleost fin or in other tissues undergoing repair., (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

The strategies or drugs for preventing and treating Hyperuricemia (HUA) are still lacking. As a traditional Chinese medicine (TCM) with a profound history, Ampelopsis grossedentata has been shown to play diverse biological roles. The purpose of the present study was to evaluate hypouricemic effect of A. grossedentata, and investigate its involved material basis and mechanism. A HUA mice model was established to evaluate the therapeutic effects of A. grossedentata. And then some extracts from A. grossedentata were prepared, isolated and analyzed. Furthermore, network pharmacology, based on the above results, was used to discover potential active ingredients and therapeutic targets, and they were further verified and explored by molecular docking and in vitro experiments. In vivo experiments showed that A. grossedentata exerted hypouricemic effect on mice of HUA. The core active ingredients (quercetin, myricetin and dihydromyricetin etc.) and core targets (PTGS2, XOD and ABCG2 etc.) for A. grossedentata to treat HUA were predicted by network pharmacology. And molecular docking showed that the spontaneous binding activities of above components and targets were marvelous. In vitro experiments further demonstrated that A. grossedentata exerted hypouricemic effect by decreasing the levels of UA, XOD, antioxidant factors, inflammatory factors, GLUT9 and URAT1 in HK-2 cells of HUA. Taken together, this study integrates multi-level interaction network with in vivo/vitro experiments to systematically reveal the material basis and mechanism of A. grossedentata in treating HUA, which provides a scientific basis for further study of A. grossedentata and HUA., 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.)

Multi-modal combination therapy for tumor is expected to have superior therapeutic effect compared with monotherapy. In this study, a super-small bismuth/copper-gallic acid coordination polymer nanoparticle (BCN) protected by polyvinylpyrrolidone is designed, which is co-encapsulated with glucose oxidase (GOX) by phospholipid to obtain nanoprobe BCGN@L. It shows that BCN has an average size of 1.8 ± 0.7 nm, and photothermal conversion of BCGN@L is 31.35% for photothermal imaging and photothermal therapy (PTT). During the treatment process of 4T1 tumor-bearing nude mice, GOX catalyzes glucose in the tumor to generate gluconic acid and hydrogen peroxide (H 2 O 2 ), which reacts with copper ions (Cu 2+ ) to produce toxic hydroxyl radicals (•OH) for chemodynamic therapy (CDT) and new fresh oxygen (O 2 ) to supply to GOX for further catalysis, preventing tumor hypoxia. These reactions increase glucose depletion for starvation therapy , decrease heat shock protein expression, and enhance tumor sensitivity to low-temperature PTT. The in vitro and in vivo results demonstrate that the combination of CDT with other treatments produces excellent tumor growth inhibition. Blood biochemistry and histology analysis suggests that the nanoprobe has negligible toxicity. All the positive results reveal that the nanoprobe can be a promising approach for incorporation into multi-modal anticancer therapy., (© 2023 Wiley-VCH GmbH.)

Background: Microcephaly and chorioretinopathy (MCCRP) is a rare autosomal recessive (AR) disorder characterized by microcephaly, developmental delay, chorioretinopathy, and visual impairment. We characterized the long-term phenotype of an additional patient with MCCRP associated with TUBCGP4 pathogenic variants and analysed previously reported cases in the literature., Materials and Methods: Analysis of clinical and genetic data of a patient with TUBGCP4-related MCCRP followed for more than 19 years and literature search for previously reported patients with TUBCGP4 variants using PubMed, Scopus, and Google Scholar., Results: Molecular diagnosis using exome sequencing demonstrated two TUBCGP4 variants in trans: c.1669C>T (p.Arg557*) and c.1746 G>T (p.Leu582=). Clinical characteristics included microcephaly, microphthalmia, punched-out chorioretinal lesions, vision impairment, nystagmus, Tetralogy of Fallot and neurodevelopmental delay. Another six previously reported cases of TUBCGP4-related MCCRP were identified. Their clinical and genetic characteristics are compared., Conclusions: TUBCGP4-related microcephaly and chorioretinopathy, is a rare autosomal recessive neuro-ophthalmic disorder. Clinical characteristics in our proband have remained stable for two decades. The pathophysiology of this syndrome is not yet fully understood.

Torsion pendulums are widely used for the measurement of small forces. In this study, we investigated the impact of temperature fluctuations on a torsion pendulum using heating devices to modulate the environmental temperature at different specific frequencies. The response coefficient between the temperature variation and the torque of the torsion pendulum was found to vary at different frequencies, with values from 4 × 10-15 N mK-1 at 0.1 mHz to 3 × 10-13 N mK-1 at 10 mHz. A passive thermal-insulation system was used to reduce the torque response within this frequency band, which is dominated by temperature noise. The results demonstrate that this modulation method provides a useful way to independently investigate the noise in a torsion pendulum resulting from environmental temperature fluctuations over a wide frequency band., (© 2023 Author(s). Published under an exclusive license by AIP Publishing.)

Purpose: To evaluate efficacy and safety of gaboxadol for treatment of children with Angelman syndrome (AS)., Method: In this international, double-blind, phase 3 trial, we randomized children 4-12 years old with a molecular diagnosis of AS and a Clinical Global Impression (CGI)-severity score ≥3 to either daily administration of weight-based gaboxadol or matching placebo for 12 weeks. The primary endpoint was the CGI-Improvement-AS (CGI-I-AS) score at week 12. Secondary endpoints included the proportion of participants with CGI-I-AS response of ≤3 (i.e., at least "minimal improvement") and ≤2 (i.e., at least "much improvement") at week 12. Safety and tolerability were monitored throughout the study. Weight based dosing of study drug ranged from 0.125 mg/kg to 0.24 mg/kg depending on weight range., Results: Between August 2019 and November 2020, 104 participants were enrolled: participants 4-12 years old were randomly (1:1) assigned to gaboxadol (n = 47) or placebo (n = 50), and 7 other participants 2─3 years old who received gaboxadol and were assessed for safety only. All gaboxadol-treated participants and 48 of 50 placebo-treated participants completed treatment. There was no significant difference in CGI-I-AS between groups: at week 12, mean CGI-I-AS score was 3.3 (SD, 1.00) and 3.2 (SD, 1.05) in the gaboxadol and placebo groups, respectively, yielding a least squares mean difference of zero (p = 0.83). There were no between-group significant differences with respect to CGI-I-AS responses. Gaboxadol was well tolerated in all age groups of this study., Conclusions: There was no significant difference in CGI-I-AS between gaboxadol and placebo after 12 weeks of study treatment in pediatric AS participants., Clinicaltrials: GOV: NCT04106557., Competing Interests: Declaration of competing interest Christopher Keary: has received compensation from Ovid Therapeutics and Biogen for consulting and research funding from Ovid Therapeutics. Lynne Bird: has received compensation from Ovid Therapeutics, F. Hoffman-LaRoche, Biogen and Ionis for consulting, and research funding from Ovid Therapeutics, F. Hoffman-LaRoche, Biogen and Ionis. Marie-Claire de Wit: has received compensation from Roche, Ionis, GW Pharma for scientific advice committees (all compensation paid to the University Hospital). Shivkumar Hatti: has received compensation from Ovid for scientific advisory board meetings. Gali Heimer: has received compensation from Ovid Therapeutics and Biogen-Ionis for participation in advisory boards. Helen Heussler: had received compensation for conducting research from Ovid therapeutics, Zynerba Pharmaceuticals, GW pharma and Axial Biotherapeutics, and for participation in advisory boards from Zynerba Pharmaceuticals and Axial Biotherapeutics (all paid to the Centre for Clinical Trials in Rare Neurodevelopmental Disorders, Queensland Children's Hospital, Brisbane, Queensland, Australia). Alexander Kolevzon: has received compensation from Ovid Therapeutics, Acadia, Alkermes, Ritrova Therapeutics, Jaguar therapeutics, GW Pharmaceuticals, Neuren Pharmaceuticals, and Scioto Biosciences. Cesar Ochoa-Lubinoff: has received compensation from Ovid Therapeutics for consulting. Wen-Hann Tan: has received research support and/or compensation for consulting from Ovid Therapeutics, F. Hoffman-LaRoche, Biogen, and Ionis. Adera Matthews, Ying Yan, and Maxwell Adams are current or former employees of Ovid Therapeutics and may hold stock or stock options., (© 2023 Published by Elsevier Ltd on behalf of European Paediatric Neurology Society.)

Background: Previous studies have shown that F-53B exposure may be neurotoxic to animals, but there is a lack of epidemiological evidence, and its mechanism needs further investigation., Methods: Serum F-53B concentrations and Wisconsin Card Sorting Test (WCST) were evaluated in 314 growing children from Guangzhou, China, and the association between them were analyzed. To study the developmental neurotoxicity of F-53B, experiments on sucking mice exposed via placental transfer and breast milk was performed. Maternal mice were orally exposed to 4, 40, and 400 μg/L of F-53B from postnatal day 0 (GD0) to postnatal day 21 (PND 21). Several genes and proteins related to neurodevelopment, dopamine anabolism, and synaptic plasticity were examined by qPCR and western blot, respectively, while dopamine contents were detected by ELISA kit in weaning mice., Results: The result showed that F-53B was positively associated with poor WCST performance. For example, with an interquartile range increase in F-53B, the change with 95 % confidence interval (CI) of correct response (CR), and non-perseverative errors (NPE) was -2.47 (95 % CI: -3.89, -1.05, P = 0.001), 2.78 (95 % CI: 0.79, 4.76, P = 0.007), respectively. Compared with the control group, the highest exposure group of weaning mice had a longer escape latency (35.24 s vs. 51.18 s, P = 0.034) and a lesser distance movement (34.81 % vs. 21.02 %, P < 0.001) in the target quadrant, as observed from morris water maze (MWM) test. The protein expression of brain-derived neurotrophic factor (BDNF) and growth associated protein-43 (GAP-43) levels were decreased, as compared to control (0.367-fold, P < 0.001; 0.366-fold, P < 0.001; respectively). We also observed the upregulation of dopamine transporter (DAT) (2.940-fold, P < 0.001) consistent with the trend of dopamine content (1.313-fold, P < 0.001) in the hippocampus., Conclusion: Early life exposure to F-53B is associated with adverse neurobehavioral changes in developing children and weaning mice which may be modulated by dopamine-dependent synaptic plasticity., 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 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: The Sport Anxiety Scale-2 (SAS-2) is a validated measure of sports trait anxiety, with promising psychometric properties. However, its cross-cultural applicability in Chinese samples remains unexplored. Thus, the primary objectives of this study were twofold: to translate the SAS-2 into Chinese and assess the psychometric properties of the Chinese version., Methods: In Study 1, we initiated the translation of the SAS-2 into Chinese. This assessment involved bilingual Chinese students proficient in both English and Chinese. Additionally, we conducted a cross-linguistic measurement invariance analysis. In Study 2, we delved into the psychometric properties of the Chinese SAS-2 using a sample of Chinese student athletes. This examination encompassed an evaluation of its factor structure, convergent and discriminant validity, and measurement invariance across genders., Results: Our findings in Study 1 indicated no significant differences in item scores between the Chinese SAS-2 and the English version, and measurement invariance across languages. In Study 2, we uncovered that the Chinese SAS-2 and its factors exhibited excellent reliability, with Cronbach's alpha values exceeding 0.80. Confirmatory factor analyses upheld the original three-factor model, demonstrating acceptable model fit indices (CFI = 0.96, TLI = 0.93, RMSEA = 0.08). Furthermore, all three factors of the Chinese SAS-2 displayed significant and positive correlations with athlete burnout and State-Trait anxiety. Additionally, this study elucidated the mediating role of Concentration Disruption (Somatic anxiety and Concentration Disruption) in the relationship between the Trait (State) anxiety, and athlete burnout. Moreover, we identified measurement invariance of the Chinese version of the SAS-2 across genders. Finally, female college athletes exhibited significantly higher scores in somatic anxiety and worry compared to their male counterparts., Discussion: In sum, our findings affirm that the Chinese version of the SAS-2 demonstrates robust reliability and correlates effectively with related criteria, thus validating its suitability for use in a Chinese context., 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 © 2023 Zhang, Zhang, Peng, Veloo, Bailey and Tan.)

A new species of stone oak, Lithocarpustapanuliensis Harapan, W.H.Tan, Nurainas & Strijk from South Tapanuli, North Sumatra, Indonesia is described. We provide colour photographs, a distribution map and a new IUCN conservation status assessment for inclusion on the global Red List. The unique cupule morphology, particularly the shape, placement and distinctness of the cupule protuberances, are distinctive from other Lithocarpus species in the region. Ecological interactions (e.g. consumption and nesting) with Tapanuli orangutans were recorded in the field., Competing Interests: The authors have declared that no competing interests exist., (Try Surya Harapan, Wei Harn Tan, Thoriq Alfath Febriamansyah, Nurainas, Syamsuardi, Joeri Sergej Strijk.)

Background: Two polyclinics in Singapore modified systems and trained health professionals to provide person-centred Care and Support Planning (CSP) for people with diabetes within a clinical trial. We aimed to investigate health professionals' perspectives on CSP to inform future developments., Methods: Qualitative research including 23 semi-structured interviews with 13 health professionals and 3 co-ordinators. Interpretive analysis, including considerations of how different understandings, enactments, experiences and evaluative judgements of CSP clustered across health professionals, and potential causal links between them., Results: Both polyclinic teams introduced CSP and sustained it through COVID-19 disruptions. The first examples health professionals gave of CSP 'going well' all involved patients who came prepared, motivated and able to modify behaviours to improve their biomedical markers, but health professionals also said that they only occasionally saw such patients in practice. Health professionals' accounts of how they conducted CSP conversations varied: some interpretations and reported enactments were less clearly aligned with the developers' person-centred aspirations than others. Health professionals brought different communication skill repertoires to their encounters and responded variably to challenges to CSP that arose from: the linguistic and educational diversity of patients in this polyclinic context; the cultural shift that CSP involved; workload pressures; organisational factors that limited relational and informational continuity of care; and policies promoting biomedical measures as key indicators of healthcare quality. While all participants saw potential in CSP, they differed in the extent to which they recognised relational and experiential benefits of CSP (beyond biomedical benefits), and their recommendations for continuing its use beyond the clinical trial were contingent on several considerations. Our analysis shows how narrower and broader interpretive emphases and initial skill repertoires can interact with situational challenges and respectively constrain or extend health professionals' ability to refine their skills with experiential learning, reduce or enhance the potential benefits of CSP, and erode or strengthen motivation to use CSP., Conclusion: Health professionals' interpretations of CSP, along with their communication skills, interact in complex ways with other features of healthcare systems and diverse patient-circumstance scenarios. They warrant careful attention in efforts to implement and evaluate person-centred support for people with long-term conditions., (© 2023. BioMed Central Ltd., part of Springer Nature.)

The bark of Streblus indicus , a Dai medicine in China, has been listed in the Chinese Materia Medica as possessing hemostatic and analgesic properties. Ethnic medicine books record that its bark or leaves for the treatment of mumps and lymphoma. However, according to the literature survey, anti-inflammatory and analgesic studies available for leaves and branches of S. indicus have been seldom reported so far. The current study focuses on the metabolites of S. indicus bark and leaves responsible for anti-inflammatory and analgesic effects on the basis of bioactive-included acetic acid writhing, hot-plate, and xylene-induced ear swelling. The secretion of inflammatory mediators, TNF- α , IL-6, IL-1 β , IL-4, and IL-10, were evaluated for their anti-inflammatory by xylene-induced in mouse ear cells. Histological examination was used to assess the anti-inflammatory and analgesic effects of the branches and leaves of S. indicus , and Western blot analysis determined the mechanism of the methanolic extract of branches and leaves. Different metabolites of S. indicus significantly alleviated analgesic and anti-inflammatory effects, with no discernable differences among them. All metabolites decreased the levels of TNF- α , IL-1 β , and IL-6 and increased the levels of IL-4 and IL-10. The analgesic and anti-inflammatory mechanism of the methanolic extract was related to the NF- k B signaling pathway. These results not only would account for scientific knowledge for the traditional application of S. indicus , but also provide a credible theoretical foundation for the further development of anti-inflammatory and analgesic agents., 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 © 2023 Xie, Huang, Chen, Zhou, Zhou, Yang, Xu, Tan and Liu.)

Activin and Bone Morphogenetic Protein (BMP) signaling plays crucial roles in vertebrate organ formation, including osteo- and angiogenesis, and tissue homeostasis, such as neuronal maintenance. Activin and BMP signaling needs to be precisely controlled by restricted expression of shared receptors, stoichiometric composition of receptor-complexes and presence of regulatory proteins. A R206H mutation in the human (hs) BMP type I receptor hsACVR1, on the other hand, leads to excessive phosphorylation of Sons of mothers against decapentaplegic (SMAD) 1/5/8. This in turn causes increased inflammation and heterotopic ossification in soft tissues of patients suffering from Fibrodysplasia Ossificans Progressiva (FOP). Several animal models have been established to understand the spontaneous and progressive nature of FOP, but often have inherent limitations. The Japanese medaka (Oryzias latipes, ola) has recently emerged as popular model for bone research. To assess whether medaka is suitable as a potential FOP animal model, we determined the expression of Activin receptor type I (ACVR1) orthologs olaAcvr1 and olaAcvr1l with that of Activin type II receptors olaAcvr2ab, olaAcvr2ba and olaAcvr2bb in embryonic and adult medaka tissues by in situ hybridization. Further, we showed that Activin A binding properties are conserved in olaAcvr2, as are the mechanistic features in the GS-Box of both olaAcvr1 and olaAcvr1l. This consequently leads to FOP-typical elevated SMAD signaling when the medaka type I receptors carry the R206H equivalent FOP mutation. Together, this study therefore provides experimental groundwork needed to establish a unique medaka model to investigate mechanisms underlying FOP., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Trumpp et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Sclerosing skeletal dysplasias result from an imbalance between bone formation and resorption. We identified three homozygous, C-terminally truncating AXIN1 variants in seven individuals from four families affected by macrocephaly, cranial hyperostosis, and vertebral endplate sclerosis. Other frequent findings included hip dysplasia, heart malformations, variable developmental delay, and hematological anomalies. In line with AXIN1 being a central component of the β-catenin destruction complex, analyses of primary and genome-edited cells harboring the truncating variants revealed enhanced basal canonical Wnt pathway activity. All three AXIN1-truncating variants resulted in reduced protein levels and impaired AXIN1 polymerization mediated by its C-terminal DIX domain but partially retained Wnt-inhibitory function upon overexpression. Addition of a tankyrase inhibitor attenuated Wnt overactivity in the AXIN1-mutant model systems. Our data suggest that AXIN1 coordinates the action of osteoblasts and osteoclasts and that tankyrase inhibitors can attenuate the effects of AXIN1 hypomorphic variants., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 American Society of Human Genetics. All rights reserved.)

Background: As the gaming industry grows around the world, playing pervasive games is becoming an important mode of entertainment. A pervasive game is one in which the game experience extends into the actual world or where the fictive world of the game merges with the physical world. How pervasive games can adapt to the ever-changing nature of technology and design in current society requires a comprehensive review., Objective: In this systematic review, we aimed to measure and analyze 4 dimensions of pervasive games through development, technology, experience, and evaluation. Moreover, we also aimed to discover and interpret their relationship with game, interaction, experience, and service design., Methods: We first chose 3 well-known databases, Web of Science, Scopus, and EBSCO, and searched from 2013 to April 2022. A strictly thorough Boolean search for research keywords such as "pervasive game," "design," and "interactive" resulted in 394 relevant articles. These articles were identified, screened, and checked for eligibility to find valid and useful articles, which were then categorized and analyzed using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) method., Results: The systematic selection was finally left with 40 valid and valuable articles. After categorization and analysis, all articles were classified according to 4 main themes, which were design and development (11/40, 28%), interaction and technology (15/40, 38%), users and experience (9/40, 23%), and evaluation and service (5/40, 13%). These 4 main areas can be subdivided into several smaller areas., Conclusions: In the 4 areas of game design, interaction design, experience design, and service design, many scholars have studied pervasive games and made contributions. Although the development and technology of pervasive games have evolved with the times, there is still a need to strengthen emerging design concepts within pervasive games., (©Liu Kai, Wee Hoe Tan, Erni Marlina Saari. Originally published in JMIR Serious Games (https://games.jmir.org), 22.08.2023.)

In the current study, we examined adaptive skills and trajectories over time in 257 individuals with Angelman syndrome (AS) using the Vineland Adaptive Behavior Scales, 2nd Edition. Multilevel linear models were used to examine differences between molecular subtypes over time, from one year to 13 years of age, in the adaptive domains of communication, daily living skills, socialization and motor skills. Individuals with non-deletion subtypes typically demonstrated a higher level of adaptive skills compared to those with deletion subtypes. Statistically significant growth was observed in all adaptive domains through at least early adolescence. Individuals with AS should continue to receive developmental services and educational supports through adolescence and into adulthood given the slow rates of growth being observed across adaptive domains., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Angelman syndrome (AS) is a rare neurodevelopmental disorder characterized by the absence of a functional UBE3A gene, which causes developmental, behavioral, and medical challenges. While currently untreatable, comprehensive data could help identify appropriate endpoints assessing meaningful improvements in clinical trials. Herein are reported the results from the FREESIAS study assessing the feasibility and utility of in-clinic and at-home measures of key AS symptoms., Methods: Fifty-five individuals with AS (aged < 5 years: n = 16, 5-12 years: n = 27, ≥ 18 years: n = 12; deletion genotype: n = 40, nondeletion genotype: n = 15) and 20 typically developing children (aged 1-12 years) were enrolled across six USA sites. Several clinical outcome assessments and digital health technologies were tested, together with overnight 19-lead electroencephalography (EEG) and additional polysomnography (PSG) sensors. Participants were assessed at baseline (Clinic Visit 1), 12 months later (Clinic Visit 2), and during intermittent home visits., Results: The participants achieved high completion rates for the clinical outcome assessments (adherence: 89-100% [Clinic Visit 1]; 76-91% [Clinic Visit 2]) and varied feasibility of and adherence to digital health technologies. The coronavirus disease 2019 (COVID-19) pandemic impacted participants' uptake of and/or adherence to some measures. It also potentially impacted the at-home PSG/EEG recordings, which were otherwise feasible. Participants achieved Bayley-III results comparable to the available natural history data, showing similar scores between individuals aged ≥ 18 and 5-12 years. Also, participants without a deletion generally scored higher on most clinical outcome assessments than participants with a deletion. Furthermore, the observed AS EEG phenotype of excess delta-band power was consistent with prior reports., Conclusions: Although feasible clinical outcome assessments and digital health technologies are reported herein, further improved assessments of meaningful AS change are needed. Despite the COVID-19 pandemic, remote assessments facilitated high adherence levels and the results suggested that at-home PSG/EEG might be a feasible alternative to the in-clinic EEG assessments. Taken altogether, the combination of in-clinic/at-home clinical outcome assessments, digital health technologies, and PSG/EEG may improve protocol adherence, reduce patient burden, and optimize study outcomes in AS and other rare disease populations., (© 2023. The Author(s).)