Using best practices to produce creative, relatable, contextualized health messaging contributes to effective risk communication. During emergency disasters, the landscape of mis- and dis-information demands strategic, collaborative approaches across all stakeholders particularly government and the media to ensure effective public messaging. However, tools for new RCCE practitioners and media agencies such as television producers and advertising firms to rapidly create effective RCCE products are currently not readily available. In response to concerns that vaccine hesitancy may become more evident once a significant proportion of the population had been reached, the Ministry of Communications and Information (MCI) in Singapore launched a public health music video on 2 May 2021, making headlines globally and garnering more than 5 million views worldwide. The video aimed to dispel myths and concerns about vaccinations and encouraged citizens to get their vaccination quickly rather than wait. We aimed to evaluate this video as a case study and articulate why it is an example of good practice in risk communications. Working inductively to identify emergent principles of product creation in this case study and analyzing them against existing RCCE frameworks and recommendations helped develop a practical tool to guide the rapid creation of RCCE products by those who may be unfamiliar to RCCE principles. This tool can help new RCCE practitioners and media agencies to produce effective products in times of crisis. The easy-to-use tool provides a brief checklist that guides rapid creation of RCCE products, including criteria for understanding the target audience, message comprehension, development, reach and impact measurement. Given its derivation from existing RCCE frameworks and health literacy concepts, these can potentially be applied across different modalities and diverse cultures. Future work would include validation of these criteria and evaluation of its utility to strengthen RCCE as core in an emergency response. Risk communication, an integral part of any emergency response, is the real-time exchange of information, advice and opinions between experts, community leaders, or officials and the people who are at risk of disease . It aimsThis paper presents a case study of a vaccination promotion video produced in Singapore to promote uptake of COVID-19 vaccines. Singapore's COVID-19 vaccination programme began on 30 December 2020, targeting healthcare and frontline workers . This wawww.gov.sg) and shared it on social media channels, making headlines globally and garnering more than 5 million views worldwide. The video aimed to dispel myths and concerns about vaccinations and encouraged citizens, especially those 45 years and older, to have their vaccination quickly rather than wait.In response to growing concerns regarding vaccine hesitancy, especially among those 45 years old and above, the Ministry of Communications and Information launched a public health music video on 2 May 2021 through the digital government portal , followed by a minority of Malays 15%), Indians (7%) and other races (1%) . Languag%, IndianRelevant concepts and frameworks for RCCE such as the WHO guidelines for risk communication, health literacy concepts and RCCE best practices were identified through a literature review on best practices in the entertainment and communication industry and evaluation tools in RCCE , 9, 11.Phua Chu Kang, the music video was launched alongside a series of videos in three main vernacular languages; Chinese, Tamil and Malay, to achieve the needed exposure  and multi-agency feedback units , 31.Findings revealed that people aged 45 years and above were concerned about the efficacy of the vaccine, and that chronic disease and existing allergies might affect their ability to tolerate the vaccine well, resulting in a wait and watch attitude.Interviews with the Public Communications Division of Ministry of Communications and Information (MCI) revealed their focus on knowing their target audience well, including their preferred media platforms and vernacular languages used. Past research showed this age group preferred simple, humourous everyday language that was relatable and without technical jargon. As such, the emergent video was easy to understand, catchy and made use of a popular celebrity.The pro-vaccination video is played by popular comedian Gurmit Singh who starred in Phua Chu Kang Pte Ltd, a drama sitcom which ran from 1997 to 2007 on local television . EvidencAuthenticity describes important technical content embedded in a context relatable to the target audience. Its importance is increasingly recognized in public health, with its longstanding challenges of audiences translating knowledge into action . While aThe music video is a combination of these crucial components. The use of characters from a long-running, familiar drama sitcom lends a relatable and distinctly Singaporean narrative format with rich contextualization. It also adopts a unique language known as “Singlish,” which is the country's distinct creole of English, Chinese dialects, Malay and Tamil, thus appealing directly to local audiences . ReferenThe team developed a checklist tool to ensure adequate understanding of the target audience including whether the target audience profile was known in terms of age, education level, their language and dialects, main sources of information, education and entertainment, their beliefs and concerns about the topic, habits, hobbies and which celebrities they admire.Health messages utilizing relatable narratives are more effective in changing behaviors than didactic recommendations of bland technical information , 25. WhiThe development team behind the video thus wrote the lyrics to the music video, ensuring short sentences written in local slang. The short duration of under 2 min of the video was intentional as was the repetitive chorus, allowing people to remember the messages easily.Comparisons have been made between this video and those in New Zealand and Australia. Similar to Singapore, New Zealand adopted a humourous approach with local vernacular, declaring “Ka kite, COVID,” meaning “see you, COVID” in the Maori language. Likewise, there is a strong relatable narrative framing vaccination as “the pathway to freedom.” Both videos target different age and ethnic groups positively, reinforcing a utilitarian worldview that “vaccination is for the community not just the individual.” This approach was in contrast to Australia's, which adopted videos with a more somber tone by senior government advisors and specialist health professionals. We were unable to assess the videos from Australia and New Zealand against our checklist due to lack of access to the producers.The campaign video of May 2021 in our case study built on the earlier March 2020 video with feedback that enabled the team to affirm the importance of message comprehension through the use of catchy tunes and simple lyrics to address ground concerns while ensuring message recall. Dialects and vernacular languages were applied more to improve for the later version.Piloting the health messaging with a focus group of the target audience to gather feedback and ensure the message resonates with them adds to the likelihood of a successful product.A challenge to good risk communication is the provision of accurate, standardized, coordinated and timely messaging that is responsive to on-ground needs and sentiments. RCCE must be conveyed in a timely, accurate manner in order to establish trust and achieve its goals to reduce transmission . This ofIn a previous music video in March 2020 at the start of the COVID-19 crisis, the same celebrity character uses a personal hygiene song to takes jabs at recent episodes of nationwide hoarding and panic buying, with rows of toilet paper and instant noodles appearing in the background, items which Singaporeans stockpiled . The relThe video contains several factually accurate and detailed health messages to build trust with the public. Accuracy of the message and its currency was ensured by collaboration with the Ministry of Health and pilot testing it with feedback groups. Understanding real time concerns via sensing mechanisms and having operational procedures for regular and nimble creation of technically accurate products is a crucial part of successful sustained community engagement.The fact that the Ministry of Communications and Information (MCI) was dedicated to producing health messaging campaigns and coordinating their production and dissemination across various government agencies and ministries reflects the government's priority to provide RCCE response as a designated strategic role in the COVID-19 outbreak response.The tool includes whether health messages are responsive to the current context, if they are factual and relevant, and whether there is a system of leadership infrastructure and governance in place to respond to evolving ground needs nimbly and to scale.The digital media landscape has changed the way information can be disseminated to populations . IncreasBesides traditional media like radio and television, the video was also released on the government's social media platforms and website, Gov.sg. A multimodal dissemination strategy can reach people of varying literary and educational backgrounds. People with lower health literacy are more likely to trust television, social media, blogs, celebrity webpages, and friends, making this video easily accessible by all . The porThe checklist in the tool developed by the team to ensure broad message reach includes media consumption platforms and practices of the target audience, and the extent of diversity in dissemination channels.Monitoring and evaluation indicators are important to measure impact, facilitate ongoing improvements and ensure sustainable funding. The tool suggests reviewing metrics and feedback on a regular basis.Post-campaign online and phone surveys assessed the campaign's impact on the consumers' attitude, message recall and campaign effectiveness in nudging behavior and changing mindsets. The “Vaccinated Chu Kang” video registered a high awareness at 78% among the respondents. Performance metrics set by the team included number of views, length of time that the video was watched by viewers, qualitative comments received on social media and media commentary.The willingness of respondents to take the COVID-19 vaccine when offered to them increased from 69% prior to the launch of the campaign in early April to 81% after the launch in mid-June. More than half of respondents who were initially undecided or chosen against vaccination indeed changed their minds and felt the campaign materials greatly or moderately helped in their decision to get vaccinated. Vaccination rates overall in Singapore displayed nearly 30% increase in the same time period .Sole attribution cannot be given to the music video as many other efforts were taking place in parallel .The tool to guide creation of RCCE products has limitations. Evaluation of the effectiveness of the single product will always be a challenge as they are never produced in isolation. For this reason, the tool focuses on creating the best opportunity for a good product. Views of representative members of target audiences as well as relevant stakeholder groups could provide useful qualitative feedback , 34, 35.Establishing RCCE products during a crisis includes resource challenges including the availability of key personnel being available to create the product quickly. Regular feedback mechanisms should be leveraged on to understand community and multistakeholder sentiments, for the tool to be adequately conceived, produced and distributed. RCCE competes with other core pillars of outbreak response and is often inappropriately deprioritised.While social media metrics are a proxy for dissemination and reach in the community, they do not reveal direct impact on behavioral change. It is also difficult to ascertain if the video produced had any significant direct impact on the target group. It is possible that the popularity of the video among the public could trickle on to the target group in the form of younger caregivers and family members urging target group members to take up the message instead of directly reaching the target audience. Focus group discussions among the target audience and their children who received the videos would more accurately reveal their sentiments toward the video and impact on perspectives. Challenges are also faced in directly correlating and attributing vaccination rates with social media metrics.RCCE products are often created intuitively in emergency settings, during which, the landscape of mis- and dis-information demands strategic, collaborative approaches across governmental, media and non-profit agencies to ensure effective public messaging. While RCCE frameworks, concepts, recommendations and evaluation tools exist, we propose a simple tool aimed at new RCCE practitioners and media agencies such as television producers and advertising firms to rapidly create effective RCCE products, which is currently not readily available. Many such operators may not even appreciate how RCCE in an emergency differs from conventional advertising. The development of a tool can enable all collaborators to produce effective products in times of crisis. Future work would include validation of these criteria and evaluation of its utility to strengthen RCCE product creation in emergency settings.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.WT, DF, and NG conceptualized the manuscript. DH contributed to the data collection and literature review. WT did the initial draft while DF, NG, and DH critically revised the manuscript. All authors have approved the final version.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.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Binge drinking refers to a pattern of alcohol consumption that leads to rapid intoxication followed by withdrawal and abstinence periods. This study aimed to investigate the potential differential contributions of impulsivity and emotion regulation difficulties to core characteristics of binge drinking  among a sample of non-abstainers college students. One thousand and five hundred fifty-five participants (17–25 years old) completed the UPPS-P Impulsive behavior scale, the Difficulties in Emotion Regulation Scale (DERS) and measures related to alcohol consumption patterns and affects by means of an online survey. Multiple regression analyses showed that UPPS-P sensation seeking, lack of premeditation, positive, and negative urgency dimensions were significantly associated with binge drinking core characteristics. More specifically, lack of premeditation, and sensation seeking dimensions were associated with speed of drinking, frequency of binge drinking epiosodes, and the ratio of binge drinking episodes. Positive urgency was associated with speed of drinking, and the ratio of binge drinking episodes while negative urgency was negatively associated with speed of drinking. DERS impulse dimension was associated with speed of drinking, DERS awareness dimension was negatively associated with the frequency of binge drinking episodes, and DERS goals dimension was significantly associated with the ratio of binge drinking episodes. Furthermore, patterns of drinking were independently associated with sex, depression and anxiety scores. These findings may help to plan and develop interventions aimed at addressing binge drinking in young adults by targeting impulsivity and emotion dysregulation. Alcohol consumption is the leading risk factor for premature mortality and disability among individuals aged 15 to 49 years old, accounting for 10% of all deaths in this age group . MoreoveGiven this Public Health concern, studies aimed to identify factors associated with BD. Several of them, as described below, highlighted the important role of impulsivity and others pointed to emotional regulation difficulties among binge drinkers.Impulsivity is viewed as a multi-faceted construct consisting of several related domains. One of these domains includes the so-called “impulsive personality traits” representing dispositional tendencies toward impulsive behavior. It is typically measured using self-report questionnaires such as the UPPS-P Impulsive Behavior Scale . This moRather than being related merely to impulsivity, BD has been associated with emotional processes and, more specifically, with emotion regulation difficulties. According to Gross , emotionStudies on emotion regulation in BD are recent and very few. Results among young adults showed that higher negative intensity  predicts greater coping-motivated drinking, and that this relationship is partially mediated by problems with emotional clarity and limited regulation strategies . Aurora An improved knowledge on BD core characteristics is a necessary step to develop better-targeted prevention and intervention programs in BD. For instance, in a part of an alcohol pharmacotherapy trial of naltrexone, Bold et al.  found thThe aim of the present study was to examine the contribution of impulsivity and emotion regulation difficulties to binge drinking observed in young adults. More specifically, we sought to individuate factors that were significantly related to the core components of this drinking pattern .We conducted an internet survey-based study on alcohol use among students from several universities located in eastern France, which consisted primarily of Caucasians. The survey was completed anonymously. The recruitment information e-mail outlined the purpose of the study and reminded participants that they were under no obligation to participate. All participants provided online informed consent before starting. No compensation was given.A total of 1,658 College students, aged between 17 years old and 25 years old, completed the whole survey. Based on the Alcohol Use Disorders Identification Test AUDIT;  we filteA revised version of the Alcohol Use Questionnaire AUQ-R;  was usedThe Alcohol Use Disorders Identification Test AUDIT;  was deveThe UPPS-P Impulsive Behavior Scale  consistsThe Difficulty in Emotion Regulation Scale DERS;  is a 36-Depression symptoms severity was assessed with the shortened Beck depression inventory BDI; . This isAnxiety symptoms severity was assessed with the Spielberger State–Trait Inventory STAI; , which iMeans and standard deviations (SD) for continuous measurements were reported when appropriated. Cronbach’s alpha was calculated for each scale and subscale.The association between demographic, clinical variables and BD core characteristics  in the whole sample was assessed by Pearson’s correlation and by generalized linear regression analyses using a forward variables selection. All variables were considered clinically relevant and selected for all regression models. BD core characteristics were included as the dependent variables, all impulsivity and emotion dysregulation dimensions as the independent variables in step 2 while controlling the other covariates in the first step  for confounding effects. Standardized β coefficients were estimated for all significant associations.The assumptions of multiple linear regression have been verified . In order to determine if multicollinearity existed in each of our three models, variable inflation factors (VIFs) were calculated for each of the independent variables . As all of the VIFs are less than 3 , it was p-values < 0.05 were regarded as statistically significant.Statistical analyses were performed using SPSS statistical software version 26.0 (IBM Corp.) and Sex, positive urgency, lack of premeditation, lack of perseverance, sensation seeking, DERS impulse, DERS awareness, and DERS clarity scores were positively correlated with consumption speed. Age was negatively correlated with consumption speed.Sex, positive urgency, lack of premeditation, lack of perseverance, and sensation seeking scores were positively correlated with BD ratio. Anxiety trait was negatively correlated with the number of drunkenness episodes.Sex, positive urgency, lack of premeditation, lack of perseverance, sensation seeking, DERS goals, DERS impulse, and DERS clarity scores were positively correlated with BD ratio.Depression severity score, anxiety score, negative urgency, DERS non-acceptance, DERS Goals, DERS impulse, and DERS strategies scores were negatively correlated with sex. Sensation seeking score was positively correlated with sex.Depression severity score, anxiety score, negative urgency, positive urgency, senstation seeking, DERS non-acceptance, DERS Goals, DERS impulse, DERS strategies, and DERS clarity scores were negatively correlated with age.Depression severity score, DERS non-acceptance, Goals, and Impulse scores were highly correlated with DERS strategies score. Positive urgency score was highly correlated with negative urgency score. All other correlations are described in Multiple regression analyses  showed tThe aim of the present study was to examine the contributions of impulsivity and emotion dysregulation dimensions to binge drinking core characteristics observed in non-abstainers young adults. Our main findings, were as follows: (1) speed of drinking, was associated with sex, depression symptoms severity score, trait anxiety score, most of impulsivity scores , and an emotion dysregulation score (i.e. Impulse), (2) the number of times being drunk in the previous 6 months was associated with sex, and with specific dimensions of impulsivity , and emotion dysregulation (i.e. Awareness), (3) the percentage of times getting drunk was associated with sex, NU, PU, PREM, SS impulsivity dimensions scores, and Goals emotion dysregulation score. To the best of our knowledge, in addition to confirming previous results regarding impulsivity, our study is the first to assess contributions of emotion dysregulation, in an integrated model including impulsivity, in this population of emerging adults.Concerning impulsivity we found that SS , was positively associated with the speed of drinking, the number of times being drunk in the previous 6 months, and with the percentage of time getting drunk when drinking. Among impulsivity and emotion dysregulation dimensions, this dimension had the greatest influence on core characteristics of binge drinking. It is suggested that among emerging adults, this dimension is a strong predictor of alcohol use . SS mighLack of premediation, defined as the tendency to act without thinking, forethought, planning and without adequate consideration of potential outcomes, was also positively associated with the three core characteristics of binge drinking in our study. This dimension of impulsivity is viewed as presenting deficits in conscientiousness . Deep inPositive urgency was associated with speed of drinking, and with percentage of times getting drunk when drinking. This dimension is suggested to predict more alcohol use during positive emotion states . MoreoveConcerning emotion regulation, we found that the Impulse dimension of the DERS was positively associated with the speed of drinking, and then seems to predispose participants to drink rapidly. The difficulties maintaining behavioral control when distressed, assessed by this DERS Impulse control difficulties subscale, describe individuals who have very strong feelings that are hard to control . MoreoveSurprisingly, Awareness dimension was negatively associated with the number of drunkenness episodes in the previous 6 months. A good emotional awareness was shown as facilitating better ability to navigate complex social situations and enjoy relationships . As sociAs expected, we highlighted an association between sex  and BD core characteristics. Sex had the greatest influence. However, this is still a topic of debate. Indeed, binge drinking in females is maybe increasing faster than binge drinking in males, and, as a result, males’ and females’ binge drinking rates are converging. Further convergence may be hard to predict and cannot be attributed entirely to females increased binge drinking . DepressDespite the meaningful findings provided by this study, it is not without limitations. A first limitation is the crosssectional design; therefore, caution is needed in inferring causality. A second limitation is based on the assessment of impulsivity, and emotion regulation through self-reports, which are subjects to possible biases. However, the validity of these questionnaires has been well supported in previous studies and our reliability indices were satisfactory. We must also bear in mind the tendency for high drinkers to underestimate consumption and drinking behavior . FinallyIn sum, the present study contributes to the literature by highlighting relationships between binge drinking core characteristics, dimensions of impulsivity, and emotional dysregulation in university students. The combination of impulsivity, and emotional dysregulation could predispose young adults to BD. Moreover, we have shown that lack of premeditation and sensation seeking impulsivity dimensions were associated with the three core features of BD. These findings have important implications for understanding risks for behaviors towards rapid and massive alcohol consumptions. Impulsivity, and emotion regulation processes will serve as important targets for prevention and treatment efforts in at-risk populations.


Objective: We aimed to quantitatively assess hand movements in patients suffering from PD using the artificial intelligence (AI)-based hand-tracking technologies of MediaPipe. Method: High-frame-rate videos and accelerometer data were recorded from 11 PD patients, two of whom showed classical Parkinsonian-type tremor. In the OFF-state and 30 Minutes after taking their standard oral medication (ON-state), video recordings were obtained. First, we investigated the frequency and amplitude relationship between the video and accelerometer data. Then, we focused on quantifying the effect of taking standard oral treatments. Results: The data extracted from the video correlated well with the accelerometer-based measurement system. Our video-based approach identified the tremor frequency with a small error rate (mean absolute error 0.229 (±0.174) Hz) and an amplitude with a high correlation. The frequency and amplitude of the hand movement before and after medication in PD patients undergoing medication differ. PD Patients experienced a decrease in the mean value for frequency from 2.012 (±1.385) Hz to 1.526 (±1.007) Hz and in the mean value for amplitude from 8.167 (±15.687) a.u. to 4.033 (±5.671) a.u. Conclusions: Our work achieved an automatic estimation of the movement frequency, including the tremor frequency with a low error rate, and to the best of our knowledge, this is the first paper that presents automated tremor analysis before/after medication in PD, in particular using high-frame-rate video data.Tremor is one of the common symptoms of Parkinson’s disease (PD). Thanks to the recent evolution of digital technologies, monitoring of PD patients’ hand movements employing contactless methods gained momentum.  Parkinson’s disease (PD) is one of the most frequent movement disorders that was first described by James Parkinson in 1817 . WorldwiDue to the evolution of digital technologies, alongside the improved capabilities of machine learning algorithms, we observe a strong increase in research activity regarding automatic monitoring of PD motor symptoms , monitorIn the literature, researchers have presented different approaches for video-based analysis. Uhríková et al.  extracteThe aforementioned studies showed the general feasibility of the approach but were limited by the need for pre-processing, manual labeling, cropping, model training, and/or ROI selection. An approach using automatic hand or hand region detection without model training could facilitate the usage of video-based hand movement/tremor analysis methods and shorten the analysis time by eliminating the labeling, algorithm training, or ROI selection process.In the following work, we performed an automatic video-based analysis of hand movement using high-frame-rate (≥180 fps) video recordings with artificial intelligence (AI)-based hand-tracking technology for before- and after-medication cases. We used the novel MediaPipe  frameworIn this section, we describe the data recording and processing process.In this study, 11 PD patients  participated. On average, they had been diagnosed with PD for 10 years . In terms of disease severity, the Hoehn and Yahr classification was between 2 and 3, and the average UPDRS Part III was 37.9 points . All patients were in-house patients of university hospital Aachen enrolled in a 3-week rehabilitation program. The accelerometer data was recorded before medication, and videos of the affected hand (in pronation position) were recorded before and after medication. Extended information, including the UPDRS on patients, is given in Accelerometer data were recorded for 30 s with the Natus Nicolet™ VikingQuest EMG/EP  equipment by the same researcher throughout the study with a standardized methodology. The subjects were sitting in a quiet temperature-controlled room. An acceleration sensor was placed on the middle phalanx of the index finger of the upper extremity of the tremor-dominant side while holding the hand still. Surface-recording EMG electrodes were placed on the wrist (data not used). The raw data of the recorded curves were then transferred to Matlab  for further analysis.The videos were taken of the tremor-dominant hand for 30 s with a camera, Lumix GH5, Kadoma, Japan (PAT001 and PAT002), GoPro HERO7, San Mateo, CA, USA . The recording settings were set to slow-motion video recording with at least 180 frames/s. Image processing was performed with Python (Python Software Foundation) and Matlab .The main data extraction and processing concept in this work aims to track the hand movements from video recordings with high accuracy and precision. We used the AI-based novel MediaPipe  hands alDepending on the hand positions , a couple of seconds from the start and end of every video were cut. From the remaining videos, 21 landmarks of the affected hand were extracted sequentially over 10 s and represented as a 10-sec long signal. Besides blur-free videos, using a high-frame-rate helps to determine the correct signal amplitude and waveform of the extracted one-dimensional signal, as its sampling frequency obviously corresponds to the frame-rate. A sample landmarks extraction is given in Since videos were recorded from a viewpoint where vertical hand movement is easy to observe, the information from the vertical (y) axis of the hand landmarks was used for video-based acceleration estimation. Both the reference accelerometer data and extracted video time-series data were band-pass filtered between 0.5–15 Hz.Generally, variations of frequency over time in tremors are expected. To observe these changes, following the filtering, both accelerometer and video time-series data  were segmented into non-overlapping 2-s long signals . The segment length of 2 s was chosen to obtain a more detailed and precise frequency spectrum in comparison to 1-s segment length.In the next step, all segmented data are converted into the frequency domain using the Fast Fourier Transform (FFT). Dominant frequency calculation from the accelerometer and estimation from video data were conducted as follows for every patient. Samples of accelerometer and video time-series data with FFT calculations are given in For the accelerometer data, the mean frequency value of 15 signal snippets was calculated. Since the goal of this work is to find only the dominant tremor frequency throughout the experiment, frequency values that deviated more than three standard deviations from the mean were considered outlier values and were eliminated automatically. To have a robust calculation of the dominant accelerometer frequency, the rest of the values were averaged, and the averaged value was noted as the dominant frequency and used as a baseline to compare the camera-based approach.During the frequency estimation from video data, some landmark points produced frequencies with a high deviation from the real accelerometer frequency see . The mosData points responsible for the outlier frequency values were excluded automatically, as described above for the accelerometer data. Additionally, to suppress the effect of pseudo/noisy landmark values and to obtain a robust frequency estimation, frequencies from the (non-excluded) landmarks were averaged, and the dominant frequency was calculated. The same method was applied both before- and after-medication. Besides frequency analysis, the amplitude analysis was also conducted by averaging the amplitudes of the maximum frequencies from the power spectrum to calculate the amplitude.This section presents the results of the frequency and amplitude estimations. First, ground-truth accelerometer data and data extracted from the videos were compared (before medication). Second, results were analyzed for before and after-medication cases (video only).In this part, the frequency distributions for the accelerometer and video data are visualized before the outlier elimination process. From A comparison of dominant frequencies between accelerometer and video data is provided in For PAT011, no accelerometer data was available. In From p-value of 7.256 × 10−7. To observe the relation between the accelerometer and data extracted from the videos, the correlation was calculated over the respective frequencies. The correlation was found to be 0.98 with a In addition to frequency calculations, amplitudes were also estimated. Results of the estimated amplitude of the accelerometer and video data are given in p-value of 2.041 × 10−9. Since the two data sources use different scales and units, extracted amplitudes cannot be compared directly. However, to observe the association between these methods, the correlation was calculated for the amplitudes. For the correlation analysis of amplitudes, we found a correlation of 1.0 with a In this study, the video-based examination of the medication effect was also explored. In From As before, we also performed an amplitude analysis additional to the frequency analysis to see the changes before and after medication. Estimated amplitudes and changes for before and after medication for the video data are given in In From In this study, our aim was a video-based analysis of tremors using high-frequency video recordings and an AI-based hand-tracking approach. To evaluate the accuracy of the video-based method, the Absolute Error between frequencies extracted with the accelerometer and with the video analysis was calculated. As seen in In the literature, there are a couple of studies that also put effort into analyzing hand movement using smartwatches ,10,11 anIn our work, different from other video-based analysis studies, we focused on analyzing the effect of medication and aimed to do this by an automated approach achieving an accurate estimation of hand movement/tremor frequency from the video. Based on the results of the other papers, it is obvious that researchers have already achieved small errors for the tremor frequency estimation, and our results are also within that range. In contrast to our work, Uhríková et al.  and WillIn the second step, we investigated the effect of medication on movement/tremor frequency and amplitude. In this work, we performed the automatic analysis of hand tremors using a video-based approach. Our study was based on employing high-frequency videos and tracking the hand via AI-based technology. In the first step, we investigated the frequency and amplitude relationship between the data extracted from the video and accelerometer. Results of the first step showed that our video-based approach can identify the tremor frequency by a small error rate (mean AE = 0.229 ± 0.174 Hz) and amplitude with a high correlation. In the second step, we focused on quantifying the effect of taking standard oral treatments like L-Dopa and dopamine agonists on tremor frequency and amplitude on video recordings. Our results suggest that patients experienced decreases in mean frequency from 2.012 ± 1.385 Hz to 1.526 ± 1.007 Hz and in mean amplitude from 8.167 ± 15.687 a.u. to 4.033 ± 5.671. Overall, our approach provides contactless automated analysis. Using this approach on a broader scale could have a significant impact in several scenarios. For one, it could make objective quantification of tremor in a medical setting easier for patients as well as the medical personnel. For another, it would allow unobtrusive tremor analysis at home, which would empower patients to supervise the progression of their disease or their response to medication with high accuracy on a daily basis.


Six anaplastic lymphoma kinase-tyrosine kinase inhibitors (ALK-TKIs), including one domestic (ensartinib) and five imported ALK-TKIs , have been recommended as first-line treatments for advanced ALK-positive NSCLC in China. This study sought to examine the cost-effectiveness of these six novel therapies in Chinese patients.via deterministic sensitivity analyses and probabilistic sensitivity analyses.We constructed a Markov model to compare the cost-effectiveness of the six ALK-TKIs as a first-line treatment for patients with advanced ALK-positive NSCLC from the perspective of the Chinese healthcare system. Transition probabilities were estimated by synthesizing data from the PROFILE 1,029 trial and a network meta-analysis. Health state utilities and costs were sourced from published literature, publicly available national databases, and local general hospitals. The robustness of model was assessed Compared with crizotinib, ensartinib achieved additional 0.12 quality-adjusted life-year (QALY) with marginal costs of $3,249, resulting in an incremental cost-effectiveness ratio (ICER) of $27,553/ QALY. When compared with ceritinib and brigatinib, ensartinib achieved additional 0.06 and 0.03 QALYs with substantially reduced costs. When compared with lorlatinib and alectinib, ensartinib was associated with a lower QALY and decreased total costs; the ICERs for lorlatinib and alectinib were $934,101/ QALY and $164,888/ QALY, respectively.For Chinese patients with advanced ALK-positive NSCLC, ensartinib was a cost-effective option compared with crizotinib, and was a dominant alternative to ceritinib and brigatinib. Although lorlatinib and alectinib were associated with prolonged survival compared with ensartinib, they were less cost-effective than ensartinib due to the overwhelming total costs. Lung cancer is an aggressive malignancy responsible for nearly one fifth of cancer-related deaths in the world . In 2020Crizotinib is an imported ALK-TKI that was firstly approved by the Chinese National Medical Products Administration (NMPA) in 2013 due to its superior clinical efficacy to conventional chemotherapies . HoweverRecently, the eXalt3 phase 3 clinical trial  investigated the efficacy of China-developed ALK-TKI ensartinib (second-generation) vs. crizotinib in the first-line setting for advanced ALK-positive NSCLC. They found that ensartinib has superior systemic and intracranial efficacy to crizotinib, as well as an overall favorable safety profile . More imTherefore, in the current study, we compared the cost-effectiveness of domestic ensartinib vs. all imported ALK-TKIs  that are recommended by the CSCO Guidelines as a first-line treatment for advanced ALK-positive NSCLC.https://www.treeage.com/) for mathematical modeling and R software  for survival fitting, we established a cost-effectiveness model to compared first-line ensartinib with crizotinib, ceritinib, alectinib, brigatinib, and lorlatinib.Using TreeAge Pro software , progressive disease (PD) and death. All patients entered the model in the PFS health state and were randomized to receive first-line ensartinib , crizotiThe primary model outputs were quality-adjusted life-year (QALY) and cost in 2021 US dollars  . We usedIndirect comparisons of the six ALK-TKIs were conducted using the survival data of crizotinib from the PROFILE 1,029 clinical trial, because crizotinib is a commonly used comparator in the clinical trials of next-generation ALK-TKIs –12, 14. other−ALK−TKIs = λcrizotinib × HR and shape γother−ALK−TKIs = γcrizotinib parameters.Given the absence of head-to-head clinical trials that directly compared these six ALK-TIKs, we used the HRs of OS and PFS for ensartinib, ceritinib, alectinib, brigatinib, and lorlatinib vs. crizotinib extracted from a published network meta-analysis (NMA)  to estimUtility assigned to each health state was obtained from a previous study that applied a Chinese-specific value algorithm to the EuroQol five-dimension (EQ-5D) questionnaire data . In addiDrugs acquisition, AEs management, routine follow-ups, subsequent anticancer therapies, BSC and palliative care costs were included in the model. The daily costs of these six items were converted by their prices according to daily dose. The prices of ensartinib, crizotinib, ceritinib, alectinib and lorlatinib were obtained from the latest available bid-winning price in the public national databases ; the priCosts of routine follow-up costs  were also estimated using data from local general hospitals. In addition, subsequent anticancer treatment, BSC and palliative care costs were extracted from previous literature .Two sensitivity analyses were carried out to test the robustness of our conclusion. Deterministic sensitivity analyses (DSA) were performed by varying individual parameters to identify sensitive factors. HRs and health state utilities varied across the published 95% confidence intervals (CIs), ALK-TKIs costs varied within specific ranges based on the Chinese national condition, other costs and disutility varied between the plus and minus 20% of the baseline values, and discounted rate varied from 0 to 8%. Probabilistic sensitivity analyses (PSA) were performed by varying multiple parameters simultaneously. Each parameter was matched with an appropriate statistical distribution, and 10,000 Monte Carlo simulations were used to generate 10,000 model outputs. For Chinese patients with advanced ALK-positive NSCLC, first-line ensartinib achieved additional 0.12, 0.06 and 0.03 QALYs in comparison with crizotinib, ceritinib, and brigatinib, respectively. The incurred total cost associated with ensartinib was marginally greater than crizotinib , but slightly lower than ceritinib  and substantially lower than brigatinib  . These rMoreover, ensartinib was associated with inferior effectiveness and lower total costs compared with lorlatinib and alectinib. The ICER between lorlatinib and ensartinib was $934,101/ QALY and between alectinib and ensartinib was $164,888/ QALY. These results indicated that lorlatinib and alectinib were not cost-effective compared with ensartinib.OS for alectinib vs. crizotinib, the daily cost of alectinib and the HROS for ensartinib vs. crizotinib. To be more specific, decreasing the HROS for alectinib vs. crizotinib from 0.67 to 0.42, decreasing the daily cost of alectinib from $84.33 to $48.74 and increasing the HROS for ensartinib vs crizotinib from 0.88 to 1.68, would allow the ICERs under the WTP threshold of $37,654 per QALY. Other model parameters had marginal influence on the model as illustrated by In DSA for alectinib vs. ensartinib, the model was particularly sensitive to the HROS for lorlatinib vs. crizotinib and the HROS for ensartinib vs. crizotinib. All other parameters varied but did not yield substantial changes in the ICER  recommended by the CSCO Guidelines for treating advanced ALK-positive NSCLC in Chinese patients.Our results demonstrated favorable effectiveness associated with alectinib and lorlatinib, which were consistent with previous clinical trials , 21–24. Sensitivity analyses revealed that HR OS plays a decisive role in determining whether the studied ALK-TKI is cost-effective or not. Due to the lack of clinical trial that directly compares these six ALK-TKIs, HRs from a systematic NMA were used for transition probabilities estimation in this economic evaluation. This NMA comparatively summarized the effectiveness and safety of several first-line ALK-TKIs by synthesizing the clinical data from all randomized controlled trials completed to date . Apart fSince the price of brigatinib is not available in Chinese mainland market, we used the price from the Hong Kong Hospital Authority to inform the cost estimation. Results from this cost-effectiveness model suggested that brigatinib was dominated by ensartinib due to a lower QALY and a greater total costs. Moreover, given the price advantage of domestic drugs and the government support, the listing price of brigatinib in Chinese mainland would unlikely be lower than that of ensartinib. Therefore, we could conservatively conclude that brigatinib does not represent as a cost-effective strategy compared with ensartinib. As for loratinib approved on April 27th, considering its superior efficacy in prolonging survival over ensartinib, we performed separate sensitivity analyses to explore the sensitive factors related to its cost-effectiveness. We found that compared with ensartinib, loratinib was not a preferred strategy regardless of its daily cost.This study has some limitations. First, although the indirect cost-effectiveness comparisons of these six ALK-TKIs were based on a well-designed comprehensive NMA analysis, further validation of our findings is necessary when head-to-head clinical trial data are available. Second, owing to the dearth of quality-of-life data specifically applicable to Chinese patients with advanced ALK-positive NSCLC, we used the health state utilities measured for advanced NSCLC patients from a Chinese-based study ; howeverIn conclusion, in this economic evaluation comparing the domestic ALK-TKI ensartinib with five imported ALK-TKIs for advanced ALK-positive NSCLC in Chinese patients, ensartinib was a cost-effective option compared with crizotinib, but a dominant alternative to ceritinib and brigatinib. Moreover, despite lorlatinib and alectinib showing superior efficacy in prolonging survival over ensartinib, their overwhelming costs made them less cost-effective than ensartinib.The original contributions presented in the study are included in the article/QL: had full access to all of the data in the study and took responsibility for the integrity of the data and the accuracy of the data analysis. XL, XZ, and LP: concept and design. XL and ZZ: drafting of the manuscript. QL: statistical analysis. XZ and XL: obtained funding. All authors: acquisition, analysis, or interpretation of data and critical revision of the manuscript for important intellectual content. All authors contributed to the article and approved the submitted version.This work was supported by the Hunan Provincial Natural Science Foundation [grant number 2021JJ40817]; Hunan Provincial Natural Science Foundation [grant number 2021JJ80080].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.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Typical genes for the treatment and diagnosis of high-grade chondrosarcoma are still in need. Our study aimed to explore the PLCD1 function in chondrosarcoma for further treatment.  Our study collected the information of 49 patients in our department. The PLCD1 expression in our cohort was detected and was compared with the TCGA database. PLCD1 knockdown and overexpression cell lines were established stably. Cell viability assay and colony formation assay were performed for cell proliferation. Flow cytometry analysis was performed for cell cycle and apoptosis. Western blotting was performed for PLCD1-related protein expression. Animal xenografts were established to verify the effect of PLCD1 in high-grade chondrosarcoma.  Compared with the TCGA database, the relation between PLCD1 expression and the malignancy of chondrosarcoma was demonstrated. A lower PLCD1 expression was detected mainly in high-grade chondrosarcoma. PLCD1 overexpression in high-grade chondrosarcoma suppressed CDKs/cyclins and induced DNA damage causing cell cycle blocking and apoptosis. Antitumor effect of PLCD1 overexpression was verified in vivo.  Lower PLCD1 was expressed in high-grade chondrosarcoma. Overexpressed PLCD1-induced DNA damage caused cell cycle blocking and apoptosis in vitro and in vivo. PLCD1 could be a novel target in high-grade chondrosarcoma for further drug development. Chondrosarcoma (CS) is one of the most primary bone tumors, and development of novel treatment is still in need for the poor prognosis of high-grade chondrosarcoma –3. HallmPhospholipase C (PLC) is an important enzyme in the phosphoinositide metabolism –7, and PRecent research has demonstrated that PLCD1 shows obvious antitumor effects such as decreasing cell proliferation in breast cancer, esophageal squamous cell carcinoma, and colon-rectal cancer –15. AntiThe patients admitted to our department from 2009 to 2015 and diagnosed with chondrosarcoma were included in our study. The tumor tissues of the patients were fixed in neutral buffered formalin and processed routinely with paraffin embedding. Three pathologists examined hematoxylin and eosin-stained glass slides from each tumor sample, and 1 paraffin block from each tumor sample was selected for immunohistochemistry (IHC). The known clinical-histological features and IHC results of patients have also been collected. The present research was approved by the Institutional Research Ethics Committee of Shanghai General Hospital, and informed consent was obtained from all patients (2008KY018).Monoclonal antibodies  were from Cell Signaling Technology . Rabbit monoclonal antibody (anti-PLCD1 (ab134936)) was obtained from Abcam Technology . Quinoline-Val-Asp-difluorophenoxymethylketone  was purchased from Selleck Chemicals . Homologous Recombination (HR) DNA Repair Antibody Sampler Kit (#99891) was purchased from Cell Signaling Technology .Human chondrosarcoma cell lines HCS-2/8  and SW13IHC assays were performed as per previous reports . ParaffiCells were seeded in 96-well plates at a density of 5000 cells per well and cultured overnight. Cell proliferation was detected by the reagent CCK-8  according to the manufacturer's instructions. The absorbance at 450 nm was measured using a microplate reader iMark .Transfections were performed using Lipofectamine 3000 (Thermo Scientific) according to the manufacturer's protocols. The sequence of targeted PLCD1 was 5′-GACGGCTTCCTCATGTACTTA-3′; the control sequence was 5′-CAACAAGATGAAGAGCACCAA-3′. Cells were transfected using the plasmids in 293T. After 48 hours, the supernatant containing packaged lentivirus was harvested and used on SW1353 cells or HCS-2/8 cells for 24 hours. Puromycin was performed to screen the stable knockdown cell lines. Overexpression plasmids were purchased from Youbio Biological Technology Co., Ltd. . According to the manufacturer's instruction, the stable overexpressed cell lines were established in SW1353 and HCS-2/8.μg of protein mixed with 5 × SDS loading buffer was loaded per lane, separated with 10% SDS-PAGE, and transferred to a polyvinylidene fluoride (PVDF) membrane . After blocking with 5% skimmed milk in TBST for 1 h at room temperature, the membrane was incubated at 4°C overnight with primary antibodies, and then, the membrane was washed three times for 10 min with TBST solution  and incubated for 1 h with the corresponding HRP-conjugated secondary antibodies . Chemiluminescent detection was performed using an ECL kit  and Bio-Rad ChemiDoc MP Imaging System . All experiments were performed in triplicate.Total protein was extracted from gathered cells with RIPA protein lysis buffer  on cold ice (4°C) in about 30 mins. The protein then was collected and centrifuged (12000 rpm) at 4°C for 20 min. The supernatant was collected, and the protein concentration of the lysates was measured using the Protein BCA Assay Kit . For the western blotting assay, 20 Cells were plated evenly in six-well plates at a density of 200 cells per well. After incubation for 2 weeks, the medium was discarded, and then, the cells were washed with PBS three times. After fixation with paraformaldehyde (4%), the colonies were stained with crystal violet (0.1%) for 15 minutes. The colony number was counted manually.5 cells per well and treated according to the requirements. Then, the cells were collected and washed with ice-cold PBS three times. The cells were resuspended in the PI staining solution  for 30 minutes, and then, the samples' cell cycle were detected by flow cytometry . The harvested cells were resuspended in the binding buffer containing Annexin V-FITC/PI . After 15 minutes of incubation in dark at room temperature, the cells' apoptosis was effectively detected by flow cytometry.Cell lines were plated evenly in six-well plates at a density of 5 × 10All animal care and experimental studies were performed according to the guidelines of the Animal Investigation Committee of the Shanghai General Hospital (2018SQ038).Male BALB/c nude mice (4–6 weeks) were maintained and bred in the animal center of Shanghai General Hospital.6 cells). After 1 week, body weight and tumor sizes were measured every three days. Tumor volume was calculated using the following equation: tumor volume = (length × width2)/2.HCS-2/8 cells and PLCD1 overexpression cells of HCS-2/8 were plated into the right flank of each nude mouse (1 × 10The tumor tissue apoptosis was detected using the TUNEL Assay Kit (Beyotime) as per manufacturer's instruction. In brief, paraffin-embedded tumor sections were deparaffinized using xylene and rehydrated ethanol and treated with proteinase K for antigen retrieval. After washing three times with PBS, the tumor sections were treated with a TUNEL detection mixture in a humidified chamber at 37°C for 1 hour. After washing with PBS, the sections were treated with DAPI staining buffer, and chosen fields at random with apoptotic cells were observed using a fluorescence microscope .https://www.cancer.gov/about-nci/organization/ccg/research/structural-genomics/tcga) and pan-cancer cell line database Cancer Cell Line Encyclopedia (CCLE) (https://sites.broadinstitute.org/ccle/) was analyzed in our study, and the survival rate according to PLCD1 expression was analyzed by online tool GEPIA (http://gepia.cancer-pku.cn/detail.php?gene=PLCD1).PLCD1 expression in Pan-cancer database The Cancer Genome Atlas (TCGA)  were considered significant.All data are presented as the mean ± standard deviation (SD) from three independent experiments at least. Fisher's exact test, unpaired Student's Histological classification of chondrosarcoma is still not clear in that related biomarker is in need to distinguish more malignant subgroup from others. Compared with the TCGA database Figures , our immTo further reveal the relation between PLCD1 expression and malignance, the stable PLCD1 knockdown/overexpression cell lines were established to verify PLCD1 function in chondrosarcoma cell lines.PLCD1 knockdown cell line (KD-PLCD1) was established based on the SW1353 cell line . The resPLCD1 overexpression cell lines (OE-PLCD1 HCS-2/8 and OE-PLCD1 SW1353) were established based on each cell line . The colCDKs and their interacted cyclins were necessary for chondrosarcoma cell proliferation . We furtDownregulated CDKs and interacted cyclins reflected a prolonged cell cycle but not the reason. We hypothesized PLCD1 overexpression induced DNA damage in chondrosarcoma cells. Western blotting revealed DNA damage response protein (CtIP and RAD54) had higher expression after PLCD1 overexpression . Unrepai2+ elevation and phosphoinositide metabolism [The enrichment of cell proliferation-related genes is one of the typical features of chondrosarcoma. Our results demonstrate that PLCD1 overexpression can inhibit cell proliferation of chondrosarcoma. PLCD1 plays a key role in regulating both Catabolism . Nakamurtabolism . Previoutabolism , leadingtabolism , 25–27. tabolism , 28.We further find out the reason of PLCD1 blocking the cell cycle by analyzing the results of the flow cytometry. PLCD1 overexpression blocks the cell cycle at the G1/S phase, and PLCD1 knockdown has an opposite effect on the cell cycle of chondrosarcoma. We hypothesize PLCD1-induced DNA damage leads to the block of the cell cycle. Our results demonstrate that the upregulation of DNA damage response proteins suggests enhanced DNA repair occurring in PLCD1 overexpressed chondrosarcoma cells. In addition, cell apoptosis detected by flow cytometry analysis suggests the PLCD1 overexpressed chondrosarcoma cells failed to repair DNA damage and caused the programmed cell death , 29.In conclusion, our study finds out that PLCD1 protein shows antitumor effect on chondrosarcoma via inhibiting cell proliferation. Overexpressed PLCD1 downregulates CDKs and interacted cyclins and induces DNA damage to cell apoptosis. PLCD1 may be a novel marker for the diagnosis of chondrosarcoma and classification of its malignancy. Drugs such as PLCD1 agonists might be useful for chondrosarcoma treatment. And PLCD1-induced DNA damage might enhance the chemotherapy sensitivity of chondrosarcoma. However, work is still moving forward for the reason that there still is no PLCD1 agonist now and PLCD1 deletion usually happens in tumor cells. A CRISPR-cas9 of the shRNA library is in need of further research.