Search

BackgroundHand function assessment heavily relies on specific task scenarios, making it challenging to ensure validity and reliability. In addition, the wide range of assessment tools, limited and expensive data recording, and analysis systems further aggravate the issue. However, smartphones provide a promising opportunity to address these challenges. Thus, the built-in, high-efficiency sensors in smartphones can be used as effective tools for hand function assessment. ObjectiveThis review aims to evaluate existing studies on hand function evaluation using smartphones. MethodsAn information specialist searched 8 databases on June 8, 2023. The search criteria included two major concepts: (1) smartphone or mobile phone or mHealth and (2) hand function or function assessment. Searches were limited to human studies in the English language and excluded conference proceedings and trial register records. Two reviewers independently screened all studies, with a third reviewer involved in resolving discrepancies. The included studies were rated according to the Mixed Methods Appraisal Tool. One reviewer extracted data on publication, demographics, hand function types, sensors used for hand function assessment, and statistical or machine learning (ML) methods. Accuracy was checked by another reviewer. The data were synthesized and tabulated based on each of the research questions. ResultsIn total, 46 studies were included. Overall, 11 types of hand dysfunction–related problems were identified, such as Parkinson disease, wrist injury, stroke, and hand injury, and 6 types of hand dysfunctions were found, namely an abnormal range of motion, tremors, bradykinesia, the decline of fine motor skills, hypokinesia, and nonspecific dysfunction related to hand arthritis. Among all built-in smartphone sensors, the accelerometer was the most used, followed by the smartphone camera. Most studies used statistical methods for data processing, whereas ML algorithms were applied for disease detection, disease severity evaluation, disease prediction, and feature aggregation. ConclusionsThis systematic review highlights the potential of smartphone-based hand function assessment. The review suggests that a smartphone is a promising tool for hand function evaluation. ML is a conducive method to classify levels of hand dysfunction. Future research could (1) explore a gold standard for smartphone-based hand function assessment and (2) take advantage of smartphones’ multiple built-in sensors to assess hand function comprehensively, focus on developing ML methods for processing collected smartphone data, and focus on real-time assessment during rehabilitation training. The limitations of the research are 2-fold. First, the nascent nature of smartphone-based hand function assessment led to limited relevant literature, affecting the evidence’s completeness and comprehensiveness. This can hinder supporting viewpoints and drawing conclusions. Second, literature quality varies due to the exploratory nature of the topic, with potential inconsistencies and a lack of high-quality reference studies and meta-analyses.

The main protease (Mpro) of SARS-CoV-2 is an attractive target in anti-COVID-19 therapy for its high conservation and major role in the virus life cycle. The covalent Mpro inhibitor nirmatrelvir (in combination with ritonavir, a pharmacokinetic enhancer) and the non-covalent inhibitor ensitrelvir have shown efficacy in clinical trials and have been approved for therapeutic use. Effective antiviral drugs are needed to fight the pandemic, while non-covalent Mpro inhibitors could be promising alternatives due to their high selectivity and favorable druggability. Numerous non-covalent Mpro inhibitors with desirable properties have been developed based on available crystal structures of Mpro. In this article, we describe medicinal chemistry strategies applied for the discovery and optimization of non-covalent Mpro inhibitors, followed by a general overview and critical analysis of the available information. Prospective viewpoints and insights into current strategies for the development of non-covalent Mpro inhibitors are also discussed.

Abstract The skeleton is a highly innervated organ in which nerve fibers interact with various skeletal cells. Peripheral nerve endings release neurogenic factors and sense skeletal signals, which mediate bone metabolism and skeletal pain. In recent years, bone tissue engineering has increasingly focused on the effects of the nervous system on bone regeneration. Simultaneous regeneration of bone and nerves through the use of materials or by the enhancement of endogenous neurogenic repair signals has been proven to promote functional bone regeneration. Additionally, emerging information on the mechanisms of skeletal interoception and the central nervous system regulation of bone homeostasis provide an opportunity for advancing biomaterials. However, comprehensive reviews of this topic are lacking. Therefore, this review provides an overview of the relationship between nerves and bone regeneration, focusing on tissue engineering applications. We discuss novel regulatory mechanisms and explore innovative approaches based on nerve–bone interactions for bone regeneration. Finally, the challenges and future prospects of this field are briefly discussed.

Abnormalities in pulmonary vasculature or technical issues during lung procurement can lead to an insufficient left atrial (LA) cuff in donors. However, surgeons frequently need to reconfigure these less-than-ideal lungs for transplantation. This case report introduces a novel technique for such reconstruction. The patient was a 35-year-old male diagnosed with pneumoconiosis for over a year. Due to progressive worsening dyspnoea leading to respiratory failure on multiple occasions, he was deemed a candidate for lung transplantation. While obtaining the donor's lung, an inadvertent short cut of the LA cuff around the left inferior pulmonary vein orifice resulted in the residual vein retracting into the pulmonary hilum. To overcome this, we employed the aortic arch for reconstruction, enabling the successful completion of the lung transplantation. On post-transplantation day 2, extracorporeal membrane oxygenation was no longer required. Mechanical ventilation ceased after 13 days, with the subsequent removal of a tracheostomy. The patient spent 35 days in the intensive care unit and 58 days in the hospital. Post-transplantation complications included primary graft dysfunction, acute kidney failure, pneumothorax in the transplanted lung, the clots in the inferior vena cava, and pneumonia. Remarkably, over a year of follow-up (19 months after lung transplantation), the patient reported no adverse events and had successfully returned to work. In this case, the aortic arch is an alternative for reconstructing an insufficient LA cuff.

In this study, the heat resistant Al–8Ce-xY (x = 0, 1, 2, and 3) alloys as designed and fabricated by gravity casting. The tensile strength of the alloys at room temperature increased with the Y addition from 117.5 to 142.7 MPa, and the tensile strength at 350 °C increased significantly from 40.4 to 57.2 MPa, which is an increase of >40%. Even after heat exposure at 350 °C for 200 h, the alloys still retain the morphology of the eutectic colony and hardness stable. The outstanding performance is primarily attributed to excellent heat stability of eutectic lamellar Al11(Ce,Y)3 phase at 350 °C and its volume fraction increased from 10.45 to 19.15% with Y additions from 0 to 3%. The increasing volume fraction of the eutectic Al11(Ce,Y)3 phase effectively improves the tensile strength of the alloys at ambient and high temperatures. Our work provides a new ternary Al–Ce–Y system which is a marvellous candidate for castable heat resistant Al alloys.

Indolylarylsulfones (IASs) are classical HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs) with a unique scaffold and possess potent antiviral activity. To address the high cytotoxicity and improve safety profiles of IASs, we introduced various sulfonamide groups linked by alkyl diamine chain to explore the entrance channel of non-nucleoside inhibitors binding pocket. 48 compounds were designed and synthesized to evaluate their anti-HIV-1 activities and reverse transcriptase inhibition activities. Especially, compound R10L4 was endowed with significant inhibitory activity towards wild-type HIV-1 (EC50(WT) = 0.007 μmol/L, SI = 30,930) as well as a panel of single-mutant strains exemplified by L100I (EC50 = 0.017 μmol/L, SI = 13,055), E138K (EC50 = 0.017 μmol/L, SI = 13,123) and Y181C (EC50 = 0.045 μmol/L, SI = 4753) which were superior to Nevirapine and Etravirine. Notably, R10L4 was characterized with significantly reduced cytotoxicity (CC50 = 216.51 μmol/L) and showed no remarkable in vivo toxic effects (acute and subacute toxicity). Moreover, the computer-based docking study was also employed to characterize the binding mode between R10L4 and HIV-1 RT. Additionally, R10L4 presented an acceptable pharmacokinetic profile. Collectively, these results deliver precious insights for next optimization and indicate that the sulfonamide IAS derivatives are promising NNRTIs for further development.

BackgroundStudies have shown that mobile apps have the potential to serve as nonpharmacological interventions for dementia care, improving the quality of life of people living with dementia and their informal caregivers. However, little is known about the needs for and privacy aspects of these mobile apps in dementia care. ObjectiveThis review seeks to understand the landscape of existing mobile apps in dementia care for people living with dementia and their caregivers with respect to app features, usability testing, privacy, and security. MethodsACM Digital Library, Cochrane Central Register of Controlled Trials, Compendex, Embase, Inspec, Ovid MEDLINE, PsycINFO, and Scopus were searched. Studies were included if they included people with dementia living in the community, their informal caregivers, or both; focused on apps in dementia care using smartphones or tablet computers; and covered usability evaluation of the app. Records were independently screened, and 2 reviewers extracted the data. The Centre for Evidence-Based Medicine critical appraisal tool and Mixed Methods Appraisal Tool were used to assess the risk of bias in the included studies. Thematic synthesis was used, and the findings were summarized and tabulated based on each research aim. ResultsOverall, 44 studies were included in this review, with 39 (89%) published after 2015. In total, 50 apps were included in the study, with more apps developed for people living with dementia as end users compared with caregivers. Most studies (27/44, 61%) used tablet computers. The most common app feature was cognitive stimulation. This review presented 9 app usability themes: user interface, physical considerations, screen size, interaction challenges, meeting user needs, lack of self-awareness of app needs, stigma, technological inexperience, and technical support. In total, 5 methods (questionnaires, interviews, observations, logging, and focus groups) were used to evaluate usability. There was little focus on the privacy and security aspects, including data transfer and protection, of mobile apps for people living with dementia. ConclusionsThe limitations of this review include 1 reviewer conducting the full-text screening, its restriction to studies published in English, and the exclusion of apps that lacked empirical usability testing. As a result, there may be an incomplete representation of the available apps in the field of dementia care. However, this review highlights significant concerns related to the usability, privacy, and security of existing mobile apps for people living with dementia and their caregivers. The findings of this review provide a valuable framework to guide app developers and researchers in the areas of privacy policy development, app development strategies, and the importance of conducting thorough usability testing for their apps. By considering these factors, future work in this field can be advanced to enhance the quality and effectiveness of dementia care apps. Trial RegistrationPROSPERO CRD42020216141; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=216141 International Registered Report Identifier (IRRID)RR2-10.1159/000514838

Abstract Background People living with dementia often exhibit behavioural and psychological symptoms of dementia that can put their and others’ safety at risk. Existing video surveillance systems in long-term care facilities can be used to monitor such behaviours of risk to alert the staff to prevent potential injuries or death in some cases. However, these behaviours of risk events are heterogeneous and infrequent in comparison to normal events. Moreover, analysing raw videos can also raise privacy concerns. Purpose In this paper, we present two novel privacy-protecting video-based anomaly detection approaches to detect behaviours of risks in people with dementia. Methods We either extracted body pose information as skeletons or used semantic segmentation masks to replace multiple humans in the scene with their semantic boundaries. Our work differs from most existing approaches for video anomaly detection that focus on appearance-based features, which can put the privacy of a person at risk and is also susceptible to pixel-based noise, including illumination and viewing direction. We used anonymized videos of normal activities to train customized spatio-temporal convolutional autoencoders and identify behaviours of risk as anomalies. Results We showed our results on a real-world study conducted in a dementia care unit with patients with dementia, containing approximately 21 h of normal activities data for training and 9 h of data containing normal and behaviours of risk events for testing. We compared our approaches with the original RGB videos and obtained a similar area under the receiver operating characteristic curve performance of 0.807 for the skeleton-based approach and 0.823 for the segmentation mask-based approach. Conclusions This is one of the first studies to incorporate privacy for the detection of behaviours of risks in people with dementia. Our research opens up new avenues to reduce injuries in long-term care homes, improve the quality of life of residents, and design privacy-aware approaches for people living in the community.

Diabetic wounds always have puzzled patients and caused serious social problems. Due to the lack of local blood vessels, severe hypoxia is generated in the defect area, which is an essential reason for the difficulty of wound healing. We have constructed a photocatalytic oxygen evolution and antibacterial biomimetic repair membrane to solve the problems of wound repair. A scanning electron microscope and transmission electron microscope characterized the biomimetic repair membrane. The oxygen evolution of the biomimetic membrane was tested by an oxygen meter. The excellent antibacterial performance of the biomimetic repair membrane was also verified by co-culture with Staphylococcus aureus and Escherichia coli. It was confirmed that the expression of collagen and HIF1-α in fibroblasts was significantly increased in vitro. And the mitochondrial activity of the vascular and nerve was increased considerably. In vivo, the healing time of diabetes wounds treated with the biomimetic repair membrane was significantly reduced, the collagen and the number of pores were increased considerably, and vascular regeneration was enhanced. The biomimetic repair membrane has an excellent performance in photocatalytic oxygen evolution and antibacterial and can significantly promote the repair of diabetes wounds. This will provide a promising treatment for diabetes wound repair.

With the progress of science and technology, humans’ ability to transform and create has been greatly enhanced, but so have the physical and mental ailments associated with environmental degradation and urbanization. Human survival and health are strongly linked to nature, and there is growing evidence that exposure to nature promotes health and well-being. However, there is currently a lack of synthesis among empirical studies on these aspects for the findings to be sufficient for informing public health strategies and social policy. Here, following basic guidelines for systematic review and meta-analysis, we searched PubMed, Web of Science, ScienceDirect, and Scopus databases in January 2023. The results of our search and analysis show that nature can improve people’s health and well-being from two aspects: physical (reduces CVDs, increases immunity, improves autonomic nervous system function, and improves sleep quality) and psychological (restores attention, improves mood, reduces stress, and improves cognitive development). The ways in which people derive health from nature are varied, and tailored, personalized, symptom-specific exposure can further increase the health benefits. More importantly, it seems that people can gain the health benefits of nature by only being exposed to it for a short time. We incorporate the existing scientific evidence in our review and develop a new heuristic point of view on the necessity of exposure to natural environments for the health of individuals.

A major challenge in brain organoid technologies is the lack of vasculature. In recent years, innovative approaches have been taken to meet this challenge. A 2020 paper published in PLOS Biology exemplifies the approaches used in this booming field.

The developing cerebral cortex of mammals is generated from nascent pyramidal neurons, which radially migrate from their birthplace in the ventral part of the neural tube to the cortical surface. Subtle aberrations in this process may cause significant changes in cortical structure and lead to developmental neurological disorders. During pyramidal neuron migration, we recently showed that the migrating neuron, which bypasses its last preceding neuron, is critical for its proper positioning and contributes to cerebral cortex thickness. Studying this process requires an imaging system with single-cell resolution and a prolonged observation window. Therefore, we built a system to maintain an organotypic brain slice on the stage of a Leica SP5 confocal microscope, which facilitated high-resolution imaging over a 12-hour time-lapse observation period of cellular events during neuron migration. Here, we share our protocol along with guidelines for overcoming difficulties during the setup. This protocol facilitates the observation of, but is not limited to, neurodevelopmental and pathological processes occurring during neuron migration.

Down syndrome (DS) is caused by the trisomy of human chromosome 21 (HSA21). A major challenge in DS research is to identify the HSA21 genes that cause specific symptoms. Down syndrome cell adhesion molecule (DSCAM) is encoded by a HSA21 gene. Previous studies have shown that the protein level of the Drosophila homolog of DSCAM determines the size of presynaptic terminals. However, whether the triplication of DSCAM contributes to presynaptic development in DS remains unknown. Here, we show that DSCAM levels regulate GABAergic synapses formed on neocortical pyramidal neurons (PyNs). In the Ts65Dn mouse model for DS, where DSCAM is overexpressed due to DSCAM triplication, GABAergic innervation of PyNs by basket and chandelier interneurons is increased. Genetic normalization of DSCAM expression rescues the excessive GABAergic innervations and the increased inhibition of PyNs. Conversely, loss of DSCAM impairs GABAergic synapse development and function. These findings demonstrate excessive GABAergic innervation and synaptic transmission in the neocortex of DS mouse models and identify DSCAM overexpression as the cause. They also implicate dysregulated DSCAM levels as a potential pathogenic driver in related neurological disorders.

Falls are one of the leading causes of injury-related deaths among the elderly worldwide. Effective detection of falls can reduce the risk of complications and injuries. Fall detection can be performed using wearable devices or ambient sensors; these methods may struggle with user compliance issues or false alarms. Video cameras provide a passive alternative; however, regular red, green, and blue (RGB) cameras are impacted by changing lighting conditions and privacy concerns. From a machine learning perspective, developing an effective fall detection system is challenging because of the rarity and variability of falls. Many existing fall detection datasets lack important real-world considerations, such as varied lighting, continuous activities of daily living (ADLs), and camera placement. The lack of these considerations makes it difficult to develop predictive models that can operate effectively in the real world. To address these limitations, we introduce a novel multi-modality dataset (MUVIM) that contains four visual modalities: infra-red, depth, RGB and thermal cameras. These modalities offer benefits such as obfuscated facial features and improved performance in low-light conditions. We formulated fall detection as an anomaly detection problem, in which a customized spatio-temporal convolutional autoencoder was trained only on ADLs so that a fall would increase the reconstruction error. Our results showed that infra-red cameras provided the highest level of performance (AUC ROC = 0.94), followed by thermal (AUC ROC = 0.87), depth (AUC ROC = 0.86) and RGB (AUC ROC = 0.83). This research provides a unique opportunity to analyze the utility of camera modalities in detecting falls in a home setting while balancing performance, passiveness, and privacy.

Behavioural symptoms of dementia present a significant risk within Long Term Care (LTC) homes, which face difficulties supporting residents and monitoring their safety with limited staffing resources. Many LTC facilities have installed video surveillance systems in common areas that can help staff to observe residents; however, typically these video streams are not monitored. In this paper, we present the development of a computer vision algorithm to use these video streams to detect episodes of clinically important agitation in people with dementia. Given that episodes of agitation are rare in comparison to normal behaviours, we formulated this as an anomaly detection problem. This involves using the video camera to monitor the scene rather than tracking individuals. We developed a customized spatio-temporal convolution autoencoder that is trained on the normal behaviours and then identified agitation during testing as anomalous behaviour. We present a proof-of-concept using video data collected from a specialized dementia unit and annotated for agitation events. We trained the unsupervised neural network on approximately 24 hours of normal activities and tested on 11 hours of videos containing both normal activities and agitation events, and obtained an area under the curve of the receiver operating characteristic curve of 0.754. This research paves the way for leveraging existing surveillance infrastructure in LTC and other mental health settings to detect agitation or aggression, with the potential for improved health and safety.

Repairing critical bone defects is a complex problem in the clinic. The periosteum rich in nerve plays a vital role in initiating and regulating bone regeneration. However, current studies have paid little attention to repairing nerves in the periosteum to promote bone regeneration. Thus, it is essential to construct bionic periosteum with the targeted injured nerves in the periosteum. We coupled phosphatidylserine (PS) targeted aptamers with repair Schwann cell exosomes to construct exosome@aptamer (EA). Then through PEI, EA was successfully built on the surface of the electrospun fiber, which was PCL@PEI@exosome@aptamer (PPEA). Through SEM, TEM, and other technologies, PPEA was characterized. Experiments prove in vivo and in vitro that it has an excellent repair effect on damaged nerves and regeneration of vascular and bones. In vivo, we confirmed that biomimetic periosteum has an apparent ability to promote nerve and bone regeneration by using Microcomputer tomography, hematoxylin-eosin, Masson, and Immunofluorescence. In vitro, we used Immunofluorescence, Real-Time Quantitative PCR, Alkaline phosphatase staining, and other tests to confirm that it has central nerve, blood vessel, and bone regeneration ability. The PPEA biomimetic periosteum has apparent neurogenic, angiogenic, and osteogenic effects. The PPEA biomimetic periosteum will provide a promising method for treating bone defects.

BackgroundUpper extremity (UE) impairment affects up to 80% of stroke survivors and accounts for most of the rehabilitation after discharge from the hospital release. Compensation, commonly used by stroke survivors during UE rehabilitation, is applied to adapt to the loss of motor function and may impede the rehabilitation process in the long term and lead to new orthopedic problems. Intensive monitoring of compensatory movements is critical for improving the functional outcomes during rehabilitation. ObjectiveThis review analyzes how technology-based methods have been applied to assess and detect compensation during stroke UE rehabilitation. MethodsWe conducted a wide database search. All studies were independently screened by 2 reviewers (XW and YF), with a third reviewer (BY) involved in resolving discrepancies. The final included studies were rated according to their level of clinical evidence based on their correlation with clinical scales (with the same tasks or the same evaluation criteria). One reviewer (XW) extracted data on publication, demographic information, compensation types, sensors used for compensation assessment, compensation measurements, and statistical or artificial intelligence methods. Accuracy was checked by another reviewer (YF). Four research questions were presented. For each question, the data were synthesized and tabulated, and a descriptive summary of the findings was provided. The data were synthesized and tabulated based on each research question. ResultsA total of 72 studies were included in this review. In all, 2 types of compensation were identified: disuse of the affected upper limb and awkward use of the affected upper limb to adjust for limited strength, mobility, and motor control. Various models and quantitative measurements have been proposed to characterize compensation. Body-worn technology (25/72, 35% studies) was the most used sensor technology to assess compensation, followed by marker-based motion capture system (24/72, 33% studies) and marker-free vision sensor technology (16/72, 22% studies). Most studies (56/72, 78% studies) used statistical methods for compensation assessment, whereas heterogeneous machine learning algorithms (15/72, 21% studies) were also applied for automatic detection of compensatory movements and postures. ConclusionsThis systematic review provides insights for future research on technology-based compensation assessment and detection in stroke UE rehabilitation. Technology-based compensation assessment and detection have the capacity to augment rehabilitation independent of the constant care of therapists. The drawbacks of each sensor in compensation assessment and detection are discussed, and future research could focus on methods to overcome these disadvantages. It is advised that open data together with multilabel classification algorithms or deep learning algorithms could benefit from automatic real time compensation detection. It is also recommended that technology-based compensation predictions be explored.

Abstract Background The rapid development of technology such as sensors and artificial intelligence in recent years enables monitoring frailty criteria to assess frailty early and accurately from a remote location such as a home. However, research shows technologies being abandoned or rejected by users due to a lack of compatibility and consumer involvement in selecting their assistive technology devices. This study aims to understand older adults’ perceptions and preferences of technologies that can potentially assess frailty at home. Methods This study collected qualitative data through focus group meetings with 15 participants ages 65 and older. Researchers asked participants questions to achieve the goal of understanding their attitudes on the technologies. These questions include (1) the concerns or barriers of installing and using the presented technology in daily life at home, (2) the reasons participants like or dislike a particular technology, (3) what makes a specific technology more acceptable, and (4) participants’ preferences in choosing technologies. Data were transcribed, coded and categorized, and finally synthesized to understand the attitudes towards presented technologies. Results Three focus group sessions were conducted with five participants in each session. In the findings, the attitudes and perspectives of participants on the technologies for assessing frailty were categorized into four themes: (A) general attitude towards using the technologies, (B) conditions for accepting certain technologies, (C) existing living habits or patterns related to using the technologies, and (D) constructive suggestions related to the technologies. Conclusions Participants generally had positive attitudes towards allowing the technologies to be installed and used at their homes. They would accept some technologies if used under certain conditions. However, questions and concerns remain, such as concerns about privacy, functionality, and aesthetics. The study also found that older adults’ living habits or patterns could affect the design and use of technology. Lastly, many valuable suggestions have been made by participants. These perspectives and insights can help improve the design and adoption of home-based frailty assessment technologies among older adults.

Artificial intelligence (AI) has a great impact on our daily living and makes our lives more efficient and productive. Especially during the coronavirus disease (COVID-19) pandemic, AI has played a key role in response to the global health crisis. There has been a boom in AI innovation and its use since the pandemic. However, despite its widespread adoption and great potential, most people have little knowledge of AI concepts and realization of its potential. The objective of this white paper is to communicate the importance of AI and its benefits to society. The report covers AI applications in six different topics from medicine (AI deployment in clinical settings, imaging and diagnostics, and acceleration of drug discovery) to more social aspects (support older adults in long-term care homes, and AI in supporting small and medium enterprises. The report ends with nine steps to consider for moving forward with AI implementation during and post pandemic period. These include legal and ethical data collection and storage, greater data access, multidisciplinary collaboration, and policy reform.

Abstract Background Dementia is a major public health concern associated with significant caregiver demands and there are technologies available to assist with caregiving. However, there is a paucity of information on caregiver needs and preferences for these technologies, particularly from a sex and gender perspective. To address this gap in research, the objectives of this study are to examine (1) the knowledge of technology, (2) perceived usefulness of technology, (3) feature preferences when installing and using technology and (4) sex and gender influences on technology needs and preferences among family caregivers of persons with dementia (PWD) across North America. Methods A secondary analysis was conducted on an existing cross-sectional survey with family caregivers of PWDs. Respondents were recruited through the Alzheimer Society of Canada, the Victorian Order of Nurses and Adult Day Programs and other Canadian health care provision institutes. Descriptive statistics, bivariate and multivariate analyses were used to describe the study sample, uncover differences between male and female caregivers and examine sex and gender influences on caregivers’ technology needs and preferences. Results A total of 381 eligible responses were received over a nine month data collection period. The majority of respondents did not know much about and never used any technologies to assist with caregiving. “Being easy to install”, “easy to learn how to use” and “cost” were identified as the most important features when purchasing and setting up technology, while “reliability” was identified as the most important feature when using technology. Most respondents were willing to pay up to $500 to acquire individual technologies. Controlling for other socio-demographic variables, female respondents were more likely to have some or more knowledge about technology for caregiving while male respondents were more willing to pay higher amounts for these technologies compared to their female counterparts. Conclusions As one of the first studies of its kind, our findings represent a step towards the incorporation of sex and gender considerations such as cost and reliability in technology design and promotion for caregivers. Future efforts are warranted to establish an in-depth understanding of sex and gender influences in relation to other social and environmental factors.

The musculoskeletal system plays a critical role in providing the physical scaffold and movement to the mammalian body. Musculoskeletal disorders severely affect mobility and quality of life and pose a heavy burden to society. This new field of musculoskeletal tissue engineering has great potential as an alternative approach to treating large musculoskeletal defects. Natural and synthetic polymers are widely used in musculoskeletal tissue engineering owing to their good biocompatibility and biodegradability. Even more promising is the use of natural and synthetic polymer composites, as well as the combination of polymers and inorganic materials, to repair musculoskeletal tissue. Therefore, this review summarizes the progress of polymer-based scaffolds for applications of musculoskeletal tissue engineering and briefly discusses the challenges and future perspectives.

Forests have provided support for human health and survival since ancient times. With improved public awareness of health issues and the importance of forest ecological functions, forest therapy has gradually gained momentum. Forest therapies have been applied around the world as preventive and alternative therapies to promote human health. As a safe, side-effect-free, low-cost, preventive, and alternative therapy, forest therapy has been scientifically proven to promote physical and mental health in humans. However, the forest therapy service system is still underdeveloped, and forest therapy has not become a mainstream part of clinical medical treatment methods in most countries worldwide. Therefore, in order to better present the development path and current situation of forest therapy in different countries and provide guidance for how other countries can develop similar interventions and clinical sites to base these activities, this study uses Germany, Japan, and China as examples to systematically tease out how forest therapy has developed and the status of forest therapy services in different countries, as well as the health benefits of forest therapy. Furthermore, the key components and traditional cultural and socioeconomic backgrounds related to forest therapy are discussed. Finally, based on published empirical research, we believe that forest therapy can be a solution to public health problems thanks to its multiple, medically proven health benefits. Forest therapy facilitates the return of people to the forest and nature to achieve health and well-being effects. However, there is a need for more research on the mechanisms (such as the immune system, endocrine system, nervous system, etc.) underlying forest therapy’s effectiveness, which should include strengthened collaborations between disciplines. In addition, the role of forest therapy services in promoting human health needs to be emphasized.

Background: Critical bone defects are a significant problem in clinics. The periosteum plays a vital role in bone regeneration. A tissue-engineered periosteum (TEP) has received increasing attention as a novel strategy for bone defect repairs. Methods: In this experiment, a biomimetic periosteum was fabricated by using coaxial electrospinning technology with decellularized porcine small intestinal submucosa (SIS) as the shell and polycaprolactone (PCL) as the core. In vitro, the effects of the biomimetic periosteum on Schwann cells, vascular endothelial cells, and bone marrow mesenchymal stem cells were detected by a scratch test, an EdU, a tube-forming test, and an osteogenesis test. In vivo, we used HE staining to evaluate the effect of the biomimetic periosteum on bone regeneration. Results: In vitro experiments showed that the biomimetic periosteum could significantly promote the formation of angiogenesis, osteogenesis, and repaired Schwann cells (SCs). In vivo experiments showed that the biomimetic periosteum could promote the repair of bone defects. Conclusions: The biomimetic periosteum could simulate the structural function of the periosteum and promote bone repair. This strategy may provide a promising method for the clinical treatment of skull bone defects.

Early identification of frailty is crucial to prevent or reverse its progression but faces challenges due to frailty’s insidious onset. Monitoring behavioral changes in real life may offer opportunities for the early identification of frailty before clinical visits. This study presented a sensor-based system that used heterogeneous sensors and cloud technologies to monitor behavioral and physical signs of frailty from home settings. We aimed to validate the concurrent validity of the sensor measurements. The sensor system consisted of multiple types of ambient sensors, a smart speaker, and a smart weight scale. The selection of these sensors was based on behavioral and physical signs associated with frailty. Older adults’ perspectives were also included in the system design. The sensor system prototype was tested in a simulated home lab environment with nine young, healthy participants. Cohen’s Kappa and Bland–Altman Plot were used to evaluate the agreements between the sensor and ground truth measurements. Excellent concurrent validity was achieved for all sensors except for the smart weight scale. The bivariate correlation between the smart and traditional weight scales showed a strong, positive correlation between the two measurements (r = 0.942, n = 24, p < 0.001). Overall, this work showed that the Frailty Toolkit (FT) is reliable for monitoring physical and behavioral signs of frailty in home settings.

A frameshift mutation in Yippee-like (YPEL) 3 was recently found from a rare human disorder with peripheral neurological conditions including hypotonia and areflexia. The YPEL gene family is highly conserved from yeast to human, but its members’ functions are poorly defined. Moreover, the pathogenicity of the human YPEL3 variant is completely unknown. We generated a Drosophila model of human YPEL3 variant and a genetic null allele of Drosophila homolog of YPEL3 (referred to as dYPEL3). Gene-trap analysis suggests that dYPEL3 is predominantly expressed in subsets of neurons, including larval nociceptors. Analysis of chemical nociception induced by allyl-isothiocyanate (AITC), a natural chemical stimulant, revealed reduced nociceptive responses in both dYPEL3 frameshift and null mutants. Subsequent circuit analysis showed reduced activation of second-order neurons (SONs) in the pathway without affecting nociceptor activation upon AITC treatment. Although the gross axonal and dendritic development of nociceptors was unaffected, the synaptic contact between nociceptors and SONs was decreased by the dYPEL3 mutations. Furthermore, expressing dYPEL3 in larval nociceptors rescued the behavioral deficit in dYPEL3 frameshift mutants, suggesting a presynaptic origin of the deficit. Together, these findings suggest that the frameshift mutation results in YPEL3 loss of function and may cause neurological conditions by weakening synaptic connections through presynaptic mechanisms.

Objective. To examine the gender, age, and region of residence in the anthropometric and nutritional profiles of children and adolescents aged 6–18 in Henan Province, China’s third most populous province. Design. This cross-sectional study of the China National Nutrition and Health survey (2010–2013) used a multistage cluster sampling technique. The sample included Chinese schoolchildren and adolescents aged 6 to 18 years (1,660 boys and 1,561 girls). Multiple logistic regression models were used to estimate the associations between sociodemographic correlates and overweight or obesity and stunting. Setting. Nine districts/counties in Henan Province. Participants. 3,221 subjects completed the questionnaire. Sociodemographic information was obtained. Body weight and height were measured. Results. There were statistically significant regional differences in average height and weight for boys in all age groups. Girls followed the same trends except for height when 15–18 years old. The urban-rural residence differences were found in relation to prevalence of stunting and weight status. Subjects in poor rural areas (15.43%) and ordinary rural areas (15.34%) had higher rates of stunting compared to their urban counterparts. Prevalence of overweight or obesity was highest in big city areas (15.71%) and lowest in ordinary rural areas (6.37%). Being a boy (OR = 1.69, 95% CI = 1.314–2.143), living in a big city (OR = 2.10, 95% CI = 1.431–3.073), or in a small-medium city (OR = 2.28, CI = 1.606–3.247), or being in a younger age group was associated with being overweight or obese. In addition, being a boy, living in a big city, or in a small-medium city, or being younger in age meant they were less likely to be stunted. Conclusions. A substantial dual burden of malnutrition among children and adolescents in Henan Province was revealed. The urban-rural differences in nutritional status were found. Stunting was more prevalent in rural areas than in urban. In contrast, while the rising problem of childhood and adolescent obesity still exists in the big city, we also found a great spike in obesity in small-medium cities. Evidence also indicated that boys were more likely to be overweight or obese. Our findings suggest that nutrition education, as well as environmental and policy interventions, is needed to target specific geographic regions.

Summary: Elucidating cell lineages provides crucial understanding of development. Recently developed sequencing-based techniques enhance the scale of lineage tracing but eliminate the spatial information offered by conventional approaches. Multi-spectral labeling techniques, such as Brainbow, have the potential to identify lineage-related cells in situ. Here, we report nuclear Bitbow (nBitbow), a “digital” version of Brainbow that greatly expands the color diversity for scoring cells, and a suite of statistical methods for quantifying the lineage relationship of any two cells. Applying these tools to the Drosophila peripheral nervous system (PNS), we determined lineage relationship between all neuronal pairs. This study demonstrates nBitbow as an efficient tool for in situ lineage mapping, and the complete lineage relationship among larval PNS neurons opens new possibilities for studying how neurons gain specific features and circuit connectivity. : Veling et al. report a multi-color labeling system and statistical methods for mapping cell lineages. They identify the lineage relationship of all neurons in the peripheral nervous system of Drosophila larvae and show the utility of this technique in mapping neurons in the CNS. Keywords: Brainbow, Bitbow, multi-spectral labeling, lineage tracing, statistics, peripheral nervous system, development, Drosophila

As an important part of the ecological infrastructure in urban areas, urban wetland parks have the significant ecological function of relieving the discomfort of people during their outdoor activities. In recent years, the specific structures and ecosystem services of urban wetland parks have been investigated from different perspectives. However, the microclimate and human thermal comfort (HTC) of urban wetland parks have rarely been discussed. In particular, the changing trends of HTC in different seasons and times have not been effectively presented. Accordingly, in this research, a monitoring platform was established in Xixi National Wetland Park, China, to continually monitor its microclimate in the long term. Via a comparison with a control site in the downtown area of Hangzhou, China, the temporal variations of the microclimate and HTC in the urban wetland park are quantified, and suggestions for clothing are also provided. The results of this study demonstrate that urban wetland parks can mitigate the heat island effect and dry island effect in summer. In addition, urban wetland parks can provide ecological services at midday during winter to mitigate the cold island effect. More importantly, urban wetland parks are found to exhibit their best performance in improving HTC during the daytime of the hot season and the midday period of the cold season. Finally, the findings of this study suggest that citizens should take protective measures and enjoy their activities in the morning, evening, or at night, not at midday in hot weather. Moreover, extra layers are suggested to be worn before going to urban wetland parks at night in cold weather, and recreational activities involving accommodation are not recommended. These findings provide not only basic scientific data for the assessment of the management and ecological health value of Xixi National Wetland Park and other urban wetland parks with subtropical monsoon climates, but also a reference for visitor timing and clothing suggestions for recreational activities.

The construction of targeted and activatable materials can largely improve the precision of disease diagnosis and therapy. However, the currently developed systems either target a transmembrane antigen or are activatable to release imaging and/or therapeutic reagents intracellularly. Here, we develop a simple thin-layer glycomaterial through the self-assembly between fluorescent glycoprobes, in which the carbohydrate-targeting reagent and the fluorophore are linked to each other by polyethylene glycol with a suitable chain length, and thin-layer manganese dioxide. The fluorogenic material developed is both capable of targeting a transmembrane glycoprotein receptor and fluorescently activatable by intracellular biothiols. The shell thickness of the material was determined to be important for achieving the biothiol-induced activation of fluorescence. This research might provide insight into the development of precision-enhanced self-assembled materials for disease theranostics.

The on-orbit single-event upset (SEU) rate of nanodevices is closely related to the orbital parameters. In this paper, the on-orbit SEU rate (OOSR) induced by a heavy ion (HI), high-energy proton (HEP) and low-energy proton (LEP) for a 65 nm SRAM device is calculated by using the software SPACE RADIATION under different orbits based on the experimental data. The results indicate that the OOSR induced by the HI, HEP and LEP varies with the orbital parameters. In particular, the orbital height, inclination and shieling thickness are the key parameters that affect the contribution of the LEP to the total OOSR. Our results provide guidance for the selection of nanodevices on different orbits.

Background: Amyloid β (Aβ) deposits and the endoplasmic reticulum stress (ERS) are both well established in the development and progression of Alzheimer's disease (AD). However, the mechanism and role of Aβ-induced ERS in AD-associated pathological progression remain to be elucidated. Methods: The five familial AD (5×FAD) mice and wild-type (WT) mice aged 2, 7, and 12 months were used in the present study. Morris water maze test was used to evaluate their cognitive performance. Immunofluorescence and Western blot analyses were used to examine the dynamic changes of pro-apoptotic (CCAAT/enhancer-binding protein homologous protein [CHOP] and cleaved caspase-12) and anti-apoptotic factors (chaperone glucose-regulated protein [GRP] 78 and endoplasmic reticulum-associated protein degradation-associated ubiquitin ligase synovial apoptosis inhibitor 1 [SYVN1]) in the ERS-associated unfolded protein response (UPR) pathway. Results: Compared with age-matched WT mice, 5×FAD mice showed higher cleaved caspase-3, lower neuron-positive staining at the age of 12 months, but earlier cognitive deficit at the age of 7 months (all P < 0.05). Interestingly, for 2-month-old 5×FAD mice, the related proteins involved in the ERS-associated UPR pathway, including CHOP, cleaved caspase-12, GRP 78, and SYVN1, were significantly increased when compared with those in age-matched WT mice (all P < 0.05). Moreover, ERS occurred mainly in neurons, not in astrocytes. Conclusions: These findings suggest that compared with those of age-matched WT mice, ERS-associated pro-apoptotic and anti-apoptotic proteins are upregulated in 2-month-old 5×FAD mice, consistent with intracellular Aβ aggregation in neurons.

As a result of rapid urbanization and urban sprawl, natural ecosystems are shrinking or are fragmented, affecting people’s health and quality of life. Modern people prefer to live in large cities rather than rural areas because of greater convenience and more comfortable living conditions. As a consequence, people are suffering from many psycho-physiological health problems and have a longing for natural environments to escape the concrete jungle. Forest therapy has emerged as a preventive and alternative therapy to cope with stress and enhance people’s health and wellbeing as a result of spending time in a green and healthy environment. Here, we review the activities related to forest therapy in China and discuss the commonalities and differences between the forest therapy types. Furthermore, we summarize the current achievements of forest therapy in basic research and the development of the forest therapy industry. We also describe the challenges that forest therapy has been facing. Finally, we provide suggestions for further development in research and industry.

Nowadays, integrated joint modules are increasingly adopted in manipulators for their advantages of high integration, miniaturization and high repeatability positioning accuracy. The problem of generally low absolute positioning accuracy (namely angle measurement accuracy) must be solved before they can be introduced into the self-driven articulated arm coordinate measuring machine which is under study in our laboratory. In this study, the sources of joint module’s angle error were analyzed and the error model based on harmonic analysis was established. Two integrated joint modules were calibrated on the self-designed calibration platform and the model parameters were deduced, respectively. The angle error was then compensated in the experiments and the results demonstrated that the angle error of the joint modules was reduced by 82.03% on average. The established angle error model can be effectively applied into the self-driven articulated arm coordinated measuring machine.

Articulated arm coordinate measuring machines (AACMMs) have been developed and applied in industrial measurement fields for more than 30 years. Manual operation is typically required during measurement, which introduces uncertain influences, such as fluctuation of measurement force, speed, and acceleration, and leads to poor reliability and reproducibility. In this paper, a novel self-driven joint model is proposed to realize automatic measurement for AACMMs. A self-driven joint is designed by combining the joint of an AACMM with a robotic arm to realize automatic rotation. A self-driven AACMM is designed using three rolling joints and three pitching joints with assigned parameters. A virtual prototype of the self-driven AACMM is established using the Adams software to simulate the driving moment of each joint. The simulation results demonstrate that the designed mechanical structure and selected devices can meet the preset requirements. Additionally, based on the proposed model, a single physical joint is developed and assembled for performance testing. Experimental results demonstrate that the model can achieve a repeatability of 1.39″ (k = 2) when the rotational velocity is less than 1.53 rad/s. Therefore, the proposed design is suitable for use in AACMMs.

Increased expression of Down Syndrome Cell Adhesion Molecule (Dscam) is implicated in the pathogenesis of brain disorders such as Down syndrome (DS) and fragile X syndrome (FXS). Here, we show that the cellular defects caused by dysregulated Dscam levels can be ameliorated by genetic and pharmacological inhibition of Abelson kinase (Abl) both in Dscam-overexpressing neurons and in a Drosophila model of fragile X syndrome. This study offers Abl as a potential therapeutic target for treating brain disorders associated with dysregulated Dscam expression.

Knowledge of the molecular and genetic mechanisms underlying the separation of dendritic and axonal compartments is not only crucial for understanding the assembly of neural circuits, but also for developing strategies to correct defective dendrites or axons in diseases with subcellular precision. Previous studies have uncovered regulators dedicated to either dendritic or axonal growth. Here we investigate a novel regulatory mechanism that differentially directs dendritic and axonal growth within the same neuron in vivo. We find that the dual leucine zipper kinase (DLK) signaling pathway in Drosophila, which consists of Highwire and Wallenda and controls axonal growth, regeneration, and degeneration, is also involved in dendritic growth in vivo. Highwire, an evolutionarily conserved E3 ubiquitin ligase, restrains axonal growth but acts as a positive regulator for dendritic growth in class IV dendritic arborization neurons in the larva. While both the axonal and dendritic functions of highwire require the DLK kinase Wallenda, these two functions diverge through two downstream transcription factors, Fos and Knot, which mediate the axonal and dendritic regulation, respectively. This study not only reveals a previously unknown function of the conserved DLK pathway in controlling dendrite development, but also provides a novel paradigm for understanding how neuronal compartmentalization and the diversity of neuronal morphology are achieved.

BackgroundCross-modal plasticity is characterized as the hypersensitivity of remaining modalities after a sensory function is lost in rodents, which ensures their awareness to environmental changes. Cellular and molecular mechanisms underlying cross-modal sensory plasticity remain unclear. We aim to study the role of different types of neurons in cross-modal plasticity.Methodology/principal findingsIn addition to behavioral tasks in mice, whole-cell recordings at the excitatory and inhibitory neurons, and their two-photon imaging, were conducted in piriform cortex. We produced a mouse model of cross-modal sensory plasticity that olfactory function was upregulated by trimming whiskers to deprive their sensory inputs. In the meantime of olfactory hypersensitivity, pyramidal neurons and excitatory synapses were functionally upregulated, as well as GABAergic cells and inhibitory synapses were downregulated in piriform cortex from the mice of cross-modal sensory plasticity, compared with controls. A crosswire connection between barrel cortex and piriform cortex was established in cross-modal plasticity.Conclusion/significanceAn upregulation of pyramidal neurons and a downregulation of GABAergic neurons strengthen the activities of neuronal networks in piriform cortex, which may be responsible for olfactory hypersensitivity after a loss of whisker tactile input. This finding provides the clues for developing therapeutic strategies to promote sensory recovery and substitution.