A fibrilação ou flutter atrial (FFA) é a arritmia cardíaca sustentada mais comum. Existem poucos dados sobre a epidemiologia da FFA na América do Sul.O presente estudo procurou descrever a epidemiologia clínica da FFA e o uso de anticoagulantes na avaliação da linha de base do Estudo Longitudinal da Saúde do Adulto (ELSA-Brasil).Foram analisados dados de 13.260 participantes do ELSA-Brasil. A FFA foi definida pelo eletrocardiograma ou por autorrelato. Modelos de regressão logística foram construídos para analisar fatores associados à FFA. Este estudo também analisou se idade e sexo estavam associados ao uso de anticoagulantes para evitar acidente vascular cerebral. O nível de significância foi de 5%.2DS2-VASc≥2, apenas 20  usavam anticoagulantes . O uso de anticoagulantes nesse grupo foi associado a maior idade . Observou-se uma tendência ao menor uso de anticoagulantes em mulheres .A idade mediana foi de 51 anos, e 7.213  participantes eram mulheres. A FFA foi detectada em 333  participantes. O aumento da idade , hipertensão  coronariopatia , insuficiência cardíaca  e febre reumática  foram associadas à FFA. Dos 185 participantes com FFA e pontuação no CHANo recrutamento do ELSA-Brasil, 2,5% dos participantes tinham FFA. O baixo uso de anticoagulantes era comum, o que representa um desafio para os cuidados de saúde nesse cenário. O objetivo do presente estudo é descrever a frequência da FFA na linha de base do ELSA-Brasil e o uso de medicamentos de prevenção de acidente vascular cerebral nos participantes com FFA e com uma pontuação CHAO desenho do ELSA-Brasil“Algum médico já disse que você tem/tinha fibrilação atrial?” Os participantes que responderam “sim” a essa pergunta também tiveram que responder “Quantos anos você tinha a primeira vez que um médico disse que você tem/tinha fibrilação atrial?”Os métodos de registro dos traçados de eletrocardiogramas (ECG) no ELSA-Brasil estão detalhados em outro artigo.O presente estudo definiu o diagnóstico de FFA na linha de base se o participante (a) tivesse um registro de eletrocardiograma com FFA na avaliação de linha de base do ELSA-Brasil (n=48) ou (b) indicasse que tinha tido um diagnóstico de fibrilação atrial numa idade inferior à sua, no momento do recrutamento para o ELSA-Brasil (n=285). A maioria das análises são apresentadas para todos os casos de FFA e de acordo com cada critério de definição.Este estudo incluiu participantes do ELSA-Brasil para os quais o diagnóstico de FFA na linha de base poderia ser avaliado. Dos 15.105 participantes do ELSA-Brasil, 663  foram excluídos por não terem uma leitura válida de eletrocardiograma na linha de base, nem uma resposta válida sobre FFA durante a reavaliação local de 2012-2014, e 1.182  foram excluídos porque tinham uma leitura válida de eletrocardiograma na linha de base sem FFA, mas não tinham uma resposta válida sobre FFA na reavaliação local de 2012-2014 . Portanto, nossa amostra principal consistiu em 13.260  participantes.2), sobrepeso (≥ 25 kg/m2 e < 30 kg/m2), e obesidade (≥ 30 kg/m2). Hipertensão foi definida pelo relato de uso de medicamento anti-hipertensivos, pressão arterial sistólica ≥ 140 mmHg, ou pressão arterial diastólica ≥ 90 mmHg no momento da avaliação de linha de base do ELSA-Brasil. Diabetes foi definido pelo histórico médico de diabetes mellitus, relato de uso de medicamentos para tratar diabetes mellitus, glicemia em jejum ≥ 126 mg/dl, níveis de HbA1c ≥ 6,5%, ou um teste oral de tolerância à glicose de 2 horas ≥ 200 mg/dl. Dislipidemia foi definida pelo relato do uso de tratamento de redução lipídica ou um nível de colesterol LDL ≥ 130 mg/dl. Obesidade abdominal foi definida como uma circunferência > 88 cm em mulheres e 102 cm em homens. Diagnósticos médicos anteriores de insuficiência cardíaca, acidente vascular cerebral, febre reumática, e evento tromboembólico foram avaliados a partir de autorrelato. Coronariopatia foi definida por um diagnóstico médico anterior de infarto do miocárdio ou angina, ou por revascularização coronária anterior. As aferições de pressão tornozelo-braquial para cálculo de índice tornozelo-braquial (ITB) são descritas detalhadamente por Miname et al.,Anatomical Therapeutic Chemical (ATC) B01AA ou B01AB. O uso de antiagregantes plaquetários foi definido como o uso de medicamentos com código ATC B01AC. Para participantes sem coronariopatia ou acidente vascular cerebral, o risco de doença cardiovascular aterosclerótica (DCVAS) de 10 anos foi calculado de acordo com as diretrizes de Avaliação de Risco Cardiovascular da ACC/AHA de 2013.2DS2-VASc foram calculadas de acordo com Lip et al.Idade, sexo, raça, grau de escolaridade, renda familiar mensal, e tabagismo foram autorrelatados e estratificados adequadamente. A renda mensal foi convertida em dólares americanos . A raça foi definida, conforme utilizada no Censo Nacional Brasileiro, ou seja, preta, parda, branca, amarela ou indígena. As medições antropométricas no ELSA-Brasil foram avaliadas utilizando técnicas padronizadas,As variáveis categóricas são apresentadas como contagens e proporções, e são comparadas usando-se o teste Qui-quadrado ou o teste exato de Fisher. As variáveis contínuas  têm distribuição não normal , e são apresentadas como medianas e faixas interquartis, e são comparadas entre os grupos, usando o teste U de Mann-Whitney. Modelos de regressão logística brutos padronizados para a idade e o sexo foram construídos para analisar se o diagnóstico de FFA na linha de base do ELSA-Brasil estava associado a idade, sexo, raça, grau de escolaridade, renda mensal, tabagismo, diagnósticos de hipertensão, diabetes e dislipidemia, índice de massa corporal, obesidade abdominal, doença arterial periférica, coronariopatia, insuficiência cardíaca, acidente vascular cerebral, febre reumática, e um risco de DCC de 10 anos > 10%. A regressão logística binária foi usada para analisar a associação com todos os casos de FFA, enquanto a regressão logística multinomial foi usada para analisar a associação com casos de FFA de acordo com cada critério de definição (por registro de eletrocardiograma ou autorrelato) separadamente. O nível de significância foi definido em 5%, e o software R, versão 3.5.1, foi usado em todas as análises.Entre os 13.260 participantes incluídos nas análises, 333  tinham FFA na linha de base do ELSA-Brasil, 176/7.213  eram mulheres e 157/6.047  eram homens. De acordo com a faixa etária, a frequência de diagnóstico de FFA foi 1,2%, 2,2%, 2,9%, e 5,4% para as idades < 45, 45-54, 55-64, e > 64 anos, respectivamente. A A 2DS2-VASc para 331  dos 333 participantes com diagnóstico de FFA na linha de base , tinham uma probabilidade mais alta de serem mulheres , e apresentaram um risco cardiovascular mais alto . Entre os 185 participantes com FFA e pontuação no CHA2DS2-VASc ≥2, apenas 20  faziam tratamento com anticoagulantes .Foi possível calcular as pontuações CHA de base . Como es2DS2-VASc ≥ 2, de acordo com idade e sexo. Considerando todos os casos de FFA, o uso de anticoagulantes foi mais frequente nos participantes com idade mais alta , e uma tendência para uso mais baixo de anticoagulantes em mulheres . A Tabela suplementar 2 mostra que a frequência do uso de anticoagulantes em homens era numericamente mais alta do que em mulheres para todas as faixas etárias. Entretanto, não foram descobertas diferenças significativas nem ao analisar todos os casos de FFA nem ao restringi-los aos participantes que apresentaram FFA no eletrocardiograma da linha de base.A 2DS2-VASc ≥ 2 não foi tratada com anticoagulantes e/ou antiagregantes plaquetários. Em terceiro lugar, o uso de anticoagulante oral foi mais comum naqueles com idade mais alta, enquanto as mulheres eram tratadas menos frequentemente.Em nossa amostra de coorte, 2,5% dos participantes incluídos apresentaram FFA na linha de base. Idade, sexo masculino, renda, e diagnósticos de hipertensão, coronariopatia, doença arterial periférica, insuficiência cardíaca e febre reumática foram associados positivamente ao FFA. Segundo, a maioria dos participantes com FFA e uma pontuação CHA,A comparação da prevalência de FFA em amostras diferentes é desafiadora devido às heterogeneidades no desenho do estudo, no cenário do estudo, e na distribuição de idade e sexo no recrutamento. Uma análise da epidemiologia global da fibrilação atrialA associação entre insuficiência cardíaca e fibrilação atrial tem importância clínica. Healey et al.2DS2-VASc ≥ 2 não foram tratados com anticoagulante. Isso é mais importante, considerando que os participantes do ELSA-Brasil tinham um grau de escolaridade médio e renda mais altos, quando comparados à população brasileira geral.Um achado notável do presente estudo foi que 89,2% de todos os participantes com FFA e uma pontuação CHAEmbora preocupantes, esses baixos índices de prescrição para prevenção de acidente vascular cerebral não são exclusividade de nossa amostra. Um estudo semelhante realizado por Healey et al.Atrial Fibrillation Follow-up Investigation of Rhythm Management , e concluíram que, comparadas aos homens, as mulheres em tratamento com varfarina passaram consideravelmente mais tempo utilizando doses inferiores à faixa terapêutica da razão normalizada internacional (RNI) (29% vs 26%). Também é importante notar que, a avaliação da linha de base do ELSA-Brasil ocorreu de 2008 a 2010. Nesse momento, o uso de anticoagulantes orais de ação direta para a prevenção de acidente vascular cerebral nos casos de FFA era muito raro.A subprescrição de medicamentos para a prevenção de acidente vascular cerebral parece ser um problema mais grave em mulheres,2DS2-VASc. O estudo também deve ser interpretado dentro de seu contexto. Conforme afirmado anteriormente, esta definição do estudo de caso pode ter uma tendência a classificações erradas por informações autorrelatadas. Embora essa estratégia minimize o sub-reconhecimento da fibrilação atrial paroxística, é importante admitir que casos autorrelatados representaram uma proporção importante de todos os casos de FFA, e isso pode ter influenciado alguns de nossos resultados. Os dados sobre a frequência de indivíduos dentro da faixa terapêutica de RNI ou escores de risco de hemorragia não estavam disponíveis. Entretanto, acreditamos que o risco de hemorragia não é suficiente para explicar uma parte significativa da falta de prevenção de acidente vascular cerebral nessa amostra.Este estudo realmente tem alguns pontos fortes. Analisamos dados de uma amostra multicêntrica grande de indivíduos que não foram recrutados de cenários clínicos. Isso reduz possíveis vieses no estudo de fatores associados à fibrilação atrial e diagnósticos, e a prescrição de medicamentos para a prevenção de acidente vascular cerebral, aproximando nossa validade externa à população geral. O protocolo abrangente do ELSA-Brasil permitiu a análise do uso de medicamento de acordo com as pontuações de risco tromboembólico CHA2DS2-VASc ≥ 2 (50% considerando apenas os diagnosticados por registros de eletrocardiograma) não foram tratados com anticoagulantes.Concluindo, foi identificada uma frequência de diagnóstico de FFA de 2,5% na avaliação de linha de base do ELSA-Brasil. Idade, sexo masculino, renda, e diagnósticos de doença arterial periférica, insuficiência cardíaca e febre reumática foram associados à FFA. Aproximadamente 90% da subamostra dos participantes com FFA e uma pontuação CHA -Atrial fibrillation is the most prevalent sustained cardiac arrythmia, with an approximate lifetime risk of 25%,2DS2-VASc scores2DS2-VASc score ≥ 2.Risk-based thromboembolic (including stroke) prevention therapy is recommended for patients with atrial fibrillation or flutter (AFF).,,,Oral anticoagulation therapy, however, still represents a challenge in clinical practice,2DS2-VASc score ≥ 2.The Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) is a large multicenter cohort of individuals of 35 to 74 years of age in six Brazilian cities, whose aim is to study the incidence and associated factors for cardiovascular diseases and diabetes. The objectives of the present study are to describe the frequency of AFF at the ELSA-Brasil baseline and the use of stroke prevention medication in participants with AFF and a CHAThe ELSA-Brasil design“Did a physician ever say that you have/had atrial fibrillation?” Participants who answered “yes” to that question were asked “How old were you the first time a physician told you that you have/had atrial fibrillation?”Methods to record electrocardiographic (ECG) tracings in ELSA-Brasil are detailed elsewhere.The present study defined AFF diagnosis at the baseline if the participant (a) had an ECG recording with AFF in the ELSA-Brasil baseline assessment (n=48) or (b) indicated that they have had an atrial fibrillation diagnosis at an age lower than his/her age upon ELSA-Brasil enrollment (n=285). Most analyses are presented for all AFF cases and according to each definition criterion.This study included ELSA-Brasil participants for whom AFF diagnosis at the baseline could be assessed. From the 15,105 ELSA-Brasil participants, 663 (4.4%) participants were excluded because they did not have a valid ECG reading at the baseline nor a valid answer for the AFF in the 2012-2014 onsite reassessment, and 1,182 (7.8%) were excluded because they had a valid ECG reading at the baseline without AFF, but without a valid answer for the AFF in the 2012-2014 onsite reassessment . Therefore, our main sample consisted of 13,260 (87.8%) participants.2), overweight (≥ 25 kg/m2 and < 30 kg/m2), and obese (≥ 30 kg/m2). Hypertension was defined as the report of the use of medications to treat hypertension, a systolic blood pressure ≥ 140 mmHg, or a diastolic blood pressure ≥ 90 mmHg upon ELSA-Brasil baseline assessment. Diabetes was defined as a medical history of diabetes mellitus, the report of the use of medications to treat diabetes mellitus, a fasting serum glucose ≥ 126 mg/dl, HbA1c levels ≥ 6.5%, or a 2-h oral glucose tolerance test ≥ 200 mg/dl. Dyslipidemia was defined as the report of the use of lipid lowering treatment or an LDL cholesterol level ≥ 130 mg/dl. Abdominal obesity was defined as a waist circumference > 88 cm in women and > 102 cm in men. Previous medical diagnosis of heart failure, stroke, rheumatic fever, and thromboembolic event were assessed by self-report. Coronary artery disease was defined by a previous medical diagnosis of myocardial infarction or angina pectoris or by previous coronary revascularization. Ankle and brachial pressure measurements for ankle-brachial index (ABI) calculation is described in detail in Miname et al.,2DS2-VASc scores were calculated according to Lip et al.Age, sex, race, level of education, monthly family income, and smoking status were self-reported and stratified accordingly. Monthly income was transformed into US dollars . Race was defined, as adopted by the Brazilian National Census, as Black, Mixed, White, Asian, and Native (Indigenous). The anthropometric measurements in the ELSA-Brasil were assessed using standard techniques,Categorical variables are presented as counts and proportions, and were compared using Chi-squared or Fisher's exact tests. Continuous variables  have non-normal distribution , and are presented as medians and interquartile ranges and compared among groups using Mann-Whitney U tests. Crude and age- and sex-adjusted logistic regression models were built to analyze if AFF diagnosis at the ELSA-Brasil baseline was associated with age, sex, race, level of education, monthly income, smoking status, hypertension, diabetes and dyslipidemia diagnoses, BMI, abdominal obesity, peripheral artery disease, coronary heart disease, heart failure, stroke, rheumatic fever, and a 10-year CHD risk > 10%. Binary logistic regression was used to analyze the association with all AFF cases, while multinomial logistic regression was used to analyze the association with AFF cases according to each definition criterion (by ECG recording or self-report) in separate. The significance level was set at 5%, and R software, version 3.5.1, was used in all analyses.Among the 13,260 participants included in the analyses, 333 (2.5%) had AFF at the ELSA-Brasil baseline, 176/7,213 (2.4%) women and 157/6,047 (2.6%) men. According to age strata, the frequency of AFF diagnosis was 1.2%, 2.2%, 2.9%, and 5.4% for ages < 45, 45-54, 55-64, and > 64 years, respectively. 2DS2-VASc scores could be calculated for 331 (99.4%) of the 333 participants with AFF diagnosis at the baseline (2DS2-VASc scores were older (p<0.001), were more likely to be women (p=0.002), and presented a higher cardiovascular risk (p<0.001). Among 185 participants with a CHA2DS2-VASc score ≥ 2, only 20 (10.8%) received anticoagulant therapy .CHAbaseline . As expe2DS2-VASc score ≥ 2, according to age and sex. Considering all AFF cases, anticoagulant use was more frequent in those with a higher age (p=0.013), and a trend towards lower anticoagulant use in women (p=0.055). Supplemental 2DS2-VASc score ≥ 2 did not receive anticoagulants and/or antiplatelet agents. Third, oral anticoagulant use was more common in those with a higher age, while women were less commonly treated.In our cohort sample, 2.5% of the included participants presented AFF at the baseline. Age, male sex, income, hypertension, coronary heart disease, peripheral artery disease, heart failure, and rheumatic fever diagnoses were positively associated with AFF. Second, most participants with AFF and a CHA,Comparing AFF prevalence across samples is challenging because of differences in study design, study setting, and age and sex distribution upon recruitment. A review of the global epidemiology of atrial fibrillationThe association between heart failure and atrial fibrillation has clinical importance. Healey et al.2DS2-VASc score ≥ 2 did not receive anticoagulants. This is more important considering that ELSA-Brasil participants have a higher mean level of education and income when compared to the general Brazilian population.A striking finding of the present study was that 89.2% of all participants with AFF and a CHAAlthough concerning, these low stroke prevention prescription rates are not exclusive to our sample. A similar study conducted by Healey et al.The under-prescription of stroke prevention medication seems to be a more severe problem in women,2DS2-VASc thromboembolic risk scores. This study must also be interpreted within its context. As stated earlier, this study's case definition may be prone to self-reported information misclassifications. Although this strategy minimizes the under-recognition of paroxysmal atrial fibrillation, it is important to acknowledge that self-reported cases were an important proportion of all AFF cases, and this may have influenced some of our results. Data on the frequency of individuals within the INR therapeutic range or on bleeding risk scores was not available. However, we believe that the risk of high bleeding is unable to explain a substantial part of the lack of stroke prevention in this sample.This study does have some strengths. We analyzed data from a large, multicenter sample of individuals who were not recruited from clinical settings. This reduces potential biases in the study of factors associated with atrial fibrillation and diagnosis and the prescription of stroke prevention medications, approximating our external validity to the general population. The comprehensive ELSA-Brasil protocol allowed for the analysis of medication use according to CHA2DS2-VASc score ≥ 2 (50% considering only those diagnosed by ECG records) did not receive anticoagulants.In conclusion, a 2.5% frequency of AFF diagnosis was found at the ELSA-Brasil baseline assessment. Age, male sex, peripheral artery disease, heart failure, or rheumatic fever diagnoses were associated with AFF. Almost 90% of the subsample of participants with AFF and a CHA


In order to improve the effect of human motion rehabilitation, a design model of human motion rehabilitation based on object-oriented technology is proposed. The entire model design process includes the following steps. First, a visual dynamic tracking model for human motion rehabilitation is established, and then a fuzzy PID (Proportion Integration Differentiation) superheterodyne control method is used to design the bone training control for human motion rehabilitation. The bone tracking control and adaptive training are under the control of object-oriented technology; it is analyzed by collecting human activity data during training. The 6-DOF kinematics problem of human movement rehabilitation is decomposed into the bone training control problem in the subspace. Combining object-oriented technology, visual blur recognition of human sports rehabilitation training, and adopting an adaptive kinematics model to design sports rehabilitation can improve the control convergence and global stability of the human sports rehabilitation process. The simulation results show that the method has a good overall steady state and the sports rehabilitation training effect is obvious. With the improvement of sports infrastructure and the development of sports, Chinese sports enthusiasm has been improved. However, in the process of rehabilitation training for injuries caused by various accidental conditions, the rehabilitation cycle of sports injuries is long due to the lack of systematic theoretical guidance and the corresponding knowledge base and it is easy to cause adverse physical injury sequelae. In order to promote the development of sports, it is necessary to systematize the theory of sports rehabilitation training. People do not know enough about sports injuries due to various accidents, especially the lack of systematic exercise rehabilitation training guidance; it is easy to cause the rehabilitation cycle to be too long and even leave the danger of the sequelae of physical injury . EspeciaRehabilitation training for physical injury has become the consensus of sports protection. This is mainly due to the fact that a large number of practices have proved that the traditional “bed rest” method for sports injury cannot complete the rehabilitation effect of sports injury, or cause the recovery of sports injury to be slower . The bodThe design process of human motion rehabilitation is an object-oriented control process. The control of human body motion rehabilitation and human-machine motion planning are typical motion planning problems with multiple constraints in high-dimensional C-space. In order to improve the effect of human sports rehabilitation, this paper presents a design model of human sports rehabilitation based on object-oriented technology and constructs a visual dynamic tracking model of human sports rehabilitation . The fuzA design model of human motion rehabilitation based on object-oriented technology is proposedFuzzy PID  superheterodyne control method is used to design the bone training control system for human movement rehabilitationCombining object-oriented technology, visual blur recognition of human sports rehabilitation training, and adopting adaptive kinematics model to design sports rehabilitationThe research contributions of the thesis mainly include the following:The rest of this paper is organized as follows. When the man-machine system model was established in the AnyBody, the complexity of the organization was negatively correlated with the efficiency of the operation. The organization model should be simplified as much as possible. The exoskeleton model is simplified as a form in which a plurality of rods are connected. The length of the rods is a fixed length and corresponds to the body segment parameters of the experimental subject, and a pedal is added to the exoskeleton to drive the ankle joint movement . Draw a It can be seen from Figures θstart ∈ Cfree (free C- space), object pose pobj, and feasible grab set gc, let the movement chain of human sports rehabilitation training model composed of waist and left (right) arm be described as {A0, A1}; the homogeneous matrix i − 1Ti(qi) between i-1 and i-1 can be expressed as T ≡ T, and then obtains the exercise rehabilitation training of human body. The IK analytic equation of model control is used to realize the sixth-degree control model design of rehabilitation human sports rehabilitation training model. Combined with kinematics model T ≡ T. Set qi and cos qi recorded as sqi and cqi, respectively. The initial motion mechanics error compensation of the human body movement rehabilitation training model is S and the body posture error compensation of the training is θstart=T.The inverse kinematics problem of 7-DOF right arm is decomposed and the control model of two degrees of freedom is obtained. The total degrees of freedom of skeletal training for human sports rehabilitation are 10. The configuration of human rehabilitation training can be expressed as The design of control error compensation based on Lyapunov method is realized. According to Barbalat's theorem,Above all, the adaptive kinematics model is used to design the sports rehabilitation; the control convergence and global stability are improved.Through the above-mentioned design, the algorithm of the optimized control model of the lower extremity exoskeleton rehabilitation robot using the Lyapunov method and the inversion technique adaptive nonlinear tracking is obtained as follows.θstart)//Set initial position RRT.SetSConfig //Generate 0∼1 random sampling probability  fr≤f Extend){//Extension to body target pose  if   ExtendStatus = if (ExtendStatus = = RRT_ERROR) {//Failed to expand    StopSearch = true}//Set stop plan marker   if (ExtendStatus = = RRT_REACHED){//Achieve goals//Get the target configurationRRT.GetConfig      RRT.GetSolutionGrasp //Get the lower limbs bone movement goal solution//Search path solution}}     FoundSolution = true  if  {//Random sampling configuration expansionθrand)//Generate random patterns   RRT.RandomConfig (θnear = RRT.NearestNeighbor (θrand)//Recently shaped    = RRT.Connect    ExtendStatus //Failed to expand StopSearch = true}}//Set stop plan markerif (ExtendStatus = = RRT_ERROR){  Cycles++//Number of searches plus 1 } while (!StopSearch && Cycles < MaxCycles && !FoundSolution) return RRT.GetSolutionPath ; }Robot optimization control model algorithm:λ1=1, λ2=1, c1=2, c2=2, the initial value of parameter adaptive estimation is ε1=0.1, and the human body is designed. The actual model parameters of sports rehabilitation training are as follows:In order to test the application performance of this method in the control of human exercise rehabilitation training, the simulation experiment is carried out. The hardware design part of the system selects ARM11 CPU as the central processor. Select ARM11 CPU S3 C6410 as the hardware core. DM9000 network card chip is used. DM9000 supports 8-bit, 16-bit, and 32-bit interface to access internal memory, and the design of control algorithm is taken. In this paper, the control parameter is selected as The state of the human skeleton is affected by many factors. In order to be closer to the actual situation, the subject must be allowed to walk in advance before the experiment is conducted, and the subject can start the experiment until it reaches a state of relaxation. As the human body walks, the left and right are basically symmetrical. This experiment only uses the right lower limb of the human body as the object of analysis.Through experiments, the joints of the hips, knees, and ankles of the right leg can be measured with time and other motion information at different speeds. The hip angle refers to the angle between the thigh and the horizontal plane, and the knee angle refers to the lower leg. Between the thighs, the angle of the ankle refers to the angle between the foot support surface and the lower leg Taking a walking pace of 3.6 km/h as an example, after processing the data, the angle of each joint angle changes over time, as shown in As you can see from The human body model is mainly composed of muscles, bones, and ligaments. By introducing the acquired action capture data files into the AnyBody, the human walking motion can be simulated and analyzed by its walking simulation module. The simulation of the walking state is shown in In the AnyBody simulation analysis, the kinematic analysis and the reverse dynamics analysis are used to obtain the kinematic information of the human body model and the information about the parameters of the muscles. The force of all muscles in the right leg during walking is obtained, as shown in In the process of walking, not all bones are subjected to a large force. In order to study the force of the bones better and analyze the force of the muscles, only a part of the major muscles can be selected as the analysis object. From On the basis of the design of the simulation environment, the control system is designed to train the rehabilitation training of human body movement, and the visual recognition output of the body movement rehabilitation training is shown in As shown in A visual dynamic tracking model for human movement rehabilitation is established.Fuzzy PID superheterodyne control method is used to design the bone training control of human movement rehabilitation.Bone tracking control and adaptive training are carried out under the control of object-oriented technology, and relevant data are collected for research.This paper presents a design model of human motion rehabilitation based on object-oriented technology. The research contributions of the thesis mainly include the following aspects:Combined with object-oriented technology, the visual blur recognition of human sports rehabilitation training and the use of adaptive kinematics model to design the sports rehabilitation process can improve the control convergence and global stability of the human sports rehabilitation process. The simulation results show that the method has a good overall steady state and the sports rehabilitation training effect is obvious. This method has good application value in guiding sports rehabilitation training.


The androgen receptor (AR) plays a central role in prostate, muscle, bone and adipose tissue. Moreover, dysregulated AR activity is a driving force in prostate cancer (PCa) initiation and progression. Consequently, antagonizing AR signalling cascades via antiandrogenic therapy is a crucial treatment option in PCa management. Besides, very high androgen levels also inhibit PCa cells’ growth, so this effect could also be applied in PCa therapy. However, on the molecular and cellular level, these mechanisms have hardly been investigated so far. Therefore, the present study describes the effects of varying androgen concentrations on the viability of PCa cells as well as localization, transactivation, and protein stability of the AR. For this purpose, cell viability was determined via WST1 assay. Alterations in AR transactivity were detected by qPCR analysis of AR target genes. A fluorescent AR fusion protein was used to analyse AR localization microscopically. Changes in AR protein expression were detected by Western blot. Our results showed that high androgen concentrations reduce the cell viability in LNCaP and C4-2 cell lines. In addition, androgens have been reported to increase AR transactivity, AR localization, and AR protein expression levels. However, high androgen levels did not reduce these parameters. Furthermore, this study revealed an androgen-induced increase in AR protein synthesis. In conclusion, inhibitory effects on cell viability by high androgen levels are due to AR downstream signalling or non-genomic AR activity. Moreover, hormonal activation of the AR leads to a self-induced stabilization of the receptor, resulting in increased AR activity. Therefore, in clinical use, a therapeutic reduction in androgen levels represents a clinical target and would lead to a decrease in AR activity and, thus, AR-driven PCa progression. AR gene on the X chromosome (Xq11-12) .Xq11-12) . The AR Xq11-12) ,7,8. It Xq11-12) ,7,8. TheXq11-12) ,10. OnceXq11-12) . Genes rXq11-12) .The AR is involved in various disorders, including androgen insensitivity syndrome, spinal bulbar muscular atrophy, hypogonadism, benign prostatic hyperplasia, and prostate cancer (PCa) ,16,17,18According to the “Cancer Today” project, PCa has the second-highest incidence of all cancers in men, with 1,414,259 new diagnosed cases worldwide and 375,304 PCa-related deaths yearly . As prolThis study aimed to investigate changes in the AR signalling after treatment with low and high androgen concentrations to identify possible concentration-dependent differences. To this end, the two AR-positive cell lines (LNCaP and C4-2) and one AR negative cell line (PC3) have been treated with different concentrations of the synthetic androgen R1881 . FollowiThe human PCa cell lines LNCaP and PC3 were obtained from the American Type Culture Collection (ATCC). Prof. Thalmann  kindly provided the C4-2 cell line . LNCaP aCell viability was analysed using the Cell Proliferation Reagent WST-1 . Cells  were seeded into 96-well culture plates. After 24 h, the medium was subsequently changed to a 50 µL medium containing 5% FCSdcc  for 24 h. After another 24 h, cells were treated with different concentrations of R1881 (0.01–10 nM). After 72 h incubation, 10 µL WST-1 solution was added for an additional 2 h. Absorbance was measured at 450 nm (Reference 620 nm) using Mithras LB 940 . After subtracting background absorbance, results were displayed as x-fold of untreated cells.®480 Software, Version 1.5  was used to determine crossing point (Cp) values. Delta (Δ)Cp = CpGOI − CpHousekeeper values were calculated and expressed as relative mRNA expression (2−ΔCp). The following primer assays have been used : AR (Hs00171172_m1), PSA/KLK3 (Hs02576345_m1), TMPRSS2 (Hs01122322_m1), PROSTEIN/SLC45A3 (Hs01026319_g1), HPRT1 (Hs02800695_m1), and TBP (Hs00427620_m1).Total RNA was isolated using the DIRECT-ZOL RNA MINIPREP  according to the manufacturer’s instructions. Superscript II RNase H Reverse Transcriptase kit was used for cDNA synthesis with 500 ng total RNA (Thermo Fisher Scientific). qPCR was performed with GoTaq Probe qPCR Master Mix  and appropriate primers for 45 cycles on a LightCycler 480 instrument . The geometric mean of HPRT1 and TBP was used for normalisation. The The LightCyclerTM 4–12% Bis-Tris protein gels separated 20 µg protein lysate. As protein standard, 5 µL Spectra Multicolour Broad Range  protein standard mixed with 1 µL MagicMarkTM XP Western Protein Standard  were used. Proteins were transferred to a nitrocellulose membrane using the iBlot Dry Blotting System . WesternBright Sirius HRP substrate  was used to detect signals and digitalised using a Microchemi chemiluminescence system . The antibodies used are listed in Cells  were seeded into 6-well culture plates for Western blot analysis. After 24 h, the medium was changed to a medium containing 5% FCSdcc . After another 24 h, cells were treated with different concentrations of R1881 (0.01–10 nM) for 72 h. Subsequently, cells were harvested, and protein concentration determination was performed as previously described . NuPAGET2O, chamber slides were finally mounted with Vectashield Hard Set mounting medium containing DAPI . The cells were visualised using a Compact Fluorescence Microscope BZ-X800E . CellProfiler 4.2.1 software has been used to calculate the nuclear/cytoplasmic intensity ratio and to measure total AR intensity [Cells (50.000 per chamber) were seeded into 8 well chamber slides and incubated for 24 h. After 24 h, the medium was changed to FCSdcc for another 24 h. For localisation studies, cells were subsequently treated with different concentrations of R1881 (0.01–10 nM) for 2 h. First, the cells were washed with PBS for staining and fixed with 4% paraformaldehyde for 10 min, followed by three times 10 min washing with PBS. Then, to permeabilise the cells, 300 µL PBS + 1% bovine serum albumin (BSA) + 0.2% Triton X100 was pipetted in each chamber for 5 min at 4 °C. The permeabilisation step was followed by a 30 min blocking step with PBS + 1% BSA. For antibody incubation, cells were incubated for 24 h with primary antibodies at 4 °C (Androgen Receptor (D6F11) XP Rabbit mAb, Cell Signaling Technology, Danvers, MA, USA, Dilution: 1:500). After 3 × 10 min washing with TBS-T, cells were incubated with the fluorescence-labelled secondary antibodies goat anti-rabbit 488  and the DNA staining dye Hoechst 33342  for 1 h. After 10 min washing with TBS-T, followed by 10 min washing with TBS, and 10 min washing with deionised Hntensity .® S3 Live-Cell Analysis .pAR-t1EosFP, a pCDNA3 expression vector coding for the AR fusion protein AREos, was provided by Dr. Marcus Cronauer  and Dr. F. Oswald  ,29. The t-test or ordinary one-way ANOVA. Data are presented as mean ± s.e.m. or mean ± s.d. to estimate the various means in multiple repeated experiments [p-values of ≤0.05 were considered statistically significant. All differences highlighted by asterisks were statistically significant .Prism 9.3  was used for statistical analysis. Differences between treatment groups were analysed using Student’s eriments . p-value−1) to 1 (100) nM. Compared to the cell viability at 1 nM, cell viability was reduced at a concentration of 10 nM R1881 in LNCaP cells  on prostate cancer cell lines, the WST-1 cell viability assay was performed on LNCaP, C4-2, and PC3 cells after R1881 treatment . IncreasaP cells . In contChange in gene transcription of AR target genes can be used as surrogates for AR-mediated transactivation. Therefore, changes in the AR target genes PSA, TMPRSS, and Prostein have been measured after treatment with different R1881 concentrations . All tested AR targets showed a concentration-dependent increase after R1881 treatment in both cell lines A–C. The ® S3 Live-Cell Analysis live-cell imager. Image analysis revealed a concentration and time-dependent increase in nuclear AR protein (To assess the influence of different concentrations of R1881 on AR localisation, PC3 cells were transfected with the fusion protein eosFP-AR A,B. Subs protein B. At 10  protein A. In lin protein B, peakin protein C.AR mRNA, LNCaP and C4-2 cells were treated for 16 h with increasing concentrations of R1881 and changes in AR mRNA were assessed using qPCR. Treatment with R1881 did not cause any change in AR mRNA levels after 16 h (The immunofluorescence experiments indicate an increase in total AR protein after R1881 treatment in LNCaP cells C. To invter 16 h A. Howeveter 16 h B–D. In Lter 16 h E.This study’s fluorescence and Western blot results indicated that R1881 increased AR protein in a transcriptional independent manner . TherefoThe AR signalling has been reported to play an essential role in several diseases, including PCa ,16,17,18p16 and p21, downregulation of MYC, CDK1, and BCL2, and induction of oxidative stress [PSA, TMPRSS2, and PROSTEIN was assessed. Both tested cell lines showed a concentration-dependent increase of the three AR target genes PSA, TMPRSS2, and PROSTEIN, reaching a plateau at 1 nM R1881. In line with previous observations, this result shows no change in AR-mediated gene transcription above 1 nM R1881 [Additionally, here, the reported biphasic effect of R1881 could be confirmed in LNCaP cells, but to a smaller extent as reported before ,34,35. Ae stress ,41,42,43e stress ,44. TherIn addition, a high concentration of R1881 had no inhibitory effects on AR localisation. However, it could be shown that high R1881 levels accelerate AR translocation to the nucleus. Moreover, the localisation study indicates an increase in AR protein levels after R1881 treatment.Increased AR protein after androgen treatment has previously been described in several studies ,46,47,48L/LPTEN  mice exhibit a 30% increase in de novo protein synthesis per cell compared to non-castrated mice [TMEFF2 translation [Additionally, here, a protein synthesis-dependent regulation of AR protein after R1881 treatment could be shown. As this increase in AR protein can already be seen after 2 h and is reversed by the protein synthesis-inhibitor CHX, there is strong evidence that non-genomic AR activity is responsible for AR stabilisation. The influence of AR on protein synthesis has already been described before ,53,54. Ited mice . It is sThis study investigated the influence of low and high concentrations of androgens on parts of the AR signalling cascade. As already reported in the literature, it could be shown that high concentrations lead to reduced cell viability of LNCaP. However, high androgen concentrations do not negatively affect AR-mediated gene expression, nuclear localisation, and AR protein stability. Therefore, the reported negative effects may be due to AR downstream targets and pathways. In addition to these results, this study demonstrated that androgen-dependent activation of the AR increases AR protein synthesis. Therefore, it can be assumed that the AR stabilises itself after activation, thus positively influencing its activity, representing a possible therapeutic target for PCa.


The refractory of castration-resistant prostate cancer (CRPC) is mainly reflected in drug resistance. The current research on the resistance mechanism of CRPC is still in its infancy. In this study, we revealed for the first time the key role of LncRNA PCBP1-AS1 in CRPC drug resistance. Through detailed in vivo and in vitro studies, we found that PCBP1-AS1 may enhance the deubiquitination of AR/AR-V7 by stabilizing the USP22-AR/AR-V7 complex, thereby preventing AR/AR-V7 from being degraded through the ubiquitin–proteasome pathway. Targeting PCBP1-AS1 can significantly restore the drug sensitivity of enzalutamide-resistant tumors in vivo and in vitro. Our research further expands the function of LncRNA in castration-resistant prostate cancer, which may provide new potential for clinical diagnosis and targeted therapy. As the most common malignant tumor in the urinary system, the treatment of prostate cancer has always been the focus of research . At presThe continuous abnormal activation of the AR signal pathway is an important factor in the progress of CRPC. At present, one of the main treatment methods for CRPC is to suppress tumors by targeting AR, such as enzalutamide. However, CRPC tumor cells through AR point mutations, AR amplification, changes of androgen biosynthesis, and other mechanisms make CRPC resistant to drugs such as enzalutamide . In receLncRNA is larger than 200 nt in length, usually cannot be translated into protein, and plays an important regulatory role in a variety of biological processes. In recent years, the importance of LncRNA in prostate cancer has been repeatedly mentioned. PCA3 has become an important indicator in the diagnosis of prostate cancer . Both HOP value <0.05, |Foldchange | >2) and screening the results, we found that PCBP1-AS1 was significantly upregulated in CRPC  to CRPC (LNCaP-AI) in an in vitro environment. After setting the threshold  for the next research. We used lentivirus targeting PCBP1-AS1 to knock down PCBP1-AS1 in LNCAP-AI and C4-2 cells Fig. . Subsequscramble) or shPCBP1-AS1 sequence (AAVPCBP1-AS1). The results after 3 weeks of tumor growth showed that compared with AAVscramble, the tumor growth rate and tumor volume in the AAVPCBP1-AS1 group were significantly decreased  from the KEGG database and applied RPI-Seq algorithm to find proteins that may have a potential relationship with PCBP1-AS1 . The res15 from tPost-transcriptional regulation includes two parts: protein synthesis and protein degradation, so we use cycloheximide (CHX) to inhibit protein synthesis with different time gradients. As can be seen from Fig. Previous experiments have confirmed that the expression of PCBP1-AS1 can inhibit the ubiquitination and degradation of AR, suggesting a potential relationship between PCBP1-AS1 and AR deubiquitination. Therefore, we hypothesized that PCBP1-AS1 can bind to members of the USP protein family of deubiquitinating enzymes. We selected USP14, USP22, and USP26 that have related studies for verification –20. AfteThe above results indicate that PCBP1-AS1 may be involved in stabilizing the USP22-AR complex. In order to further understand the combination of PCBP1-AS1 and AR, we constructed plasmids containing different AR domains: full-length AR (MYC-AR-FL), NTD, and DBD domains (MYC-AR-N + D), the plasmid contains only the NTD domain (MYC-AR-N) or both the DBD and LBD domains (MYC-AR-D + L). MYC tags were added to facilitate subsequent detection. We verified the binding region through RIP-qPCR and RNA pull-down experiments. The results suggest that PCBP1-AS1 binds to the NTD domain of AR, but not DBD or LBD domain Fig. .Based on the above results, we performed PCBP1-AS1 rescue on the LNCaP-AI and C4-2 cells of shPCBP1-AS1 Fig. . After tEnzR) and set out to verify our hypothesis . we found that compared with C4-2, the expression of PCBP1-AS1, AR, and AR-V7 in C4-2EnzR cells was further significantly improved , the expression of AR, AR-V7, KLK3, and FKBP5 all decreased significantly , C4-2 cells treated with enzalutamide (group B: C4-2D-/E + ), C4-2EnzR treated with the DMSO (group C: C4-2EnzRD + /E-), C4-2EnzR treated with the enzalutamide (group D: C4-2EnzRD-/E + ), EnzR-shLnc treated with DMSO (group E: EnzR-shLncD + /E-), EmzR-shLnc treated with enzalutamide (group F: EnzR-shLncD-/E + ). Through the MTT experiment, we found that enzalutamide can affect C4-2 cells, but not C4-2EnzR cells. Knockdown of PCBP1-AS1 in C4-2EnzR cells can significantly inhibit cell growth, while simultaneous application of enzalutamide can achieve a more significant effect . The results of in vivo experiments showed that enzalutamide had no significant effect on drug-resistant xenograft tumors. After knocking down PCBP1-AS1 Fig. , the senIn this study, we identified PCBP1-AS1 as a novel regulator of AR and AR-V7 by enhancing deubiquitination through stabilizing the USP22-AR/AR-V7 complex. PCBP1-AS1 is closely related to patients’ clinical outcomes, targeting PCBP1-AS1 can inhibit tumor growth and enzalutamide resistance. Which may provide new sight in treatment against CRPC Fig. .Fig. 6PCResearches about PCBP1-AS1 mainly focused on its role in malignant disease. Most of this research identified PCBP1-AS1 as a biomarker or a factor in ceRNA networks. Till present, PCBP1-AS1 was identified to be functional or a biomarker in hepatocellular cancer, oral carcinoma, and Hodgkin lymphoma –23. HoweThe research of LncRNA in prostate cancer, especially CRPC has been relatively mature, and previous studies have also shown the broad prospects of lncRNA in the treatment of prostate cancer. PCA3 isUbiquitination is an important post-translational protein modification and is involved in the regulation of many eukaryotic signal pathways . AbnormaOur research also has shortcomings. First, the application of PCBP1-AS1 is still under discussion. It may be feasible to use antisense oligonucleotide (ASO) to construct molecular drugs and target them by oncolytic viruses. But at present, the biological safety of ASO drugs and oncolytic viruses is not yet fully understood, and sufficient postmortem demonstrations are still needed before conducting clinical studies. In addition, the functions of genes are diversified. This study only reveals the mechanism of PCBP1-AS1 in the AR signaling pathway, the possibility that PCBP1-AS1 can regulate CRPC in an AR-independent manner cannot be denied. Third, this study only explored AR-V7, whether PCBP1-AS1 can regulate other AR splicing variants that contain intact NTD is still unknown (such as AR-V567es). In any case, our research is a breakthrough. For the first time, we have revealed the important mechanism of PCBP1-AS1 in the AR signaling pathway and its application potential in refractory CRPC, which has high clinical application value.In this study, we first revealed the important function of long noncoding RNA PCBP1-AS1 in prostate cancer. PCBP1-AS1 stabilizes the USP22-AR/AR-V7 complex, enhances the deubiquitination of AR and AR-V7, and promotes the progress of CRPC. Targeting PCBP1-AS1 can significantly enhance the sensitivity of tumors to enzalutamide in vivo and in vitro and can provide new possibilities for clinical diagnosis and targeted therapy of refractory CRPC.TCGA dataset was downloaded from the UCSC-XENA website. GSE124291 dataset was downloaded from the GEO website, which contains three repeats of LNCaP-AI cells and three repeats of LNCaP cells. As for tissue microarray, 4 BPH patients, 28 HSPC patients, and 12 CRPC patients were collected from the Affiliated Cancer Hospital of Zhengzhou University. All patients are informed and agree to our request.All detailed information can be found in Supplementary Table LNCaP and C4-2 cells were donated by Zhang Mingpeng, Institute of Urology, Tianjin Medical University Second Hospital. LNCaP-AI cells were generated from LNCaP cells. We use 1640 medium containing 10% carbon-adsorbed fetal bovine serum to continuously culture LNCaP cells to stable passages for 50 generations. When the cells can grow normally in this environment, we named this cell LNCaP-AI cell, and conduct follow-up experiments.EnzR cells are induced from C4-2 cells. We first added 1 µM of enzalutamide to the normally cultured C4-2 cells. After the remaining cells were able to grow normally, we gradually increased the concentration of enzalutamide to 2 µM, 5 µM, 10 µM, 20 µM. Subsequently, we continued to culture the cells in the environment of 20 μM enzalutamide to stable passage for 50 generations. At this time, we believed that C4-2 cells had become resistant to enzalutamide and named C4-2EnzR.C4-22. 1640 with 10% fetal bovine serum was used for C4-2 and LNCaP cells, 1640 with 10% carbon-absorbed fetal bovine serum was used for LNCaP-AI cells.As for cell culture, all cells were cultured in 37 °C cell incubator under 5% COThe extraction of cell and tissue proteins is done using RIPA. For the cells, the culture medium was first discarded and washed with PBS, then an appropriate amount of RIPA was added, placed at 4 °C for 30 min shaking, and centrifuged at 12,000 rpm for 30 min at 4 °C. Subsequently, the supernatant was aspirated, the protein concentration was determined by the Bradford method, and stored at −80 °C for later use.For western blot, mix the protein and 5× loading buffer at a ratio of 4:1 and heat at 95 for 5 min. The samples were then added to a 10% SDS-PAGE gel for electrophoresis. Use PVDF membrane for electroporation, keep it at a constant current of 250 mA for 120 min, then block with 5% skimmed milk powder for 1 h, rinse with TBST three times, and incubate overnight with the corresponding primary antibody at 4 °C. On the second day, remove the primary antibody, rinse with TBST three times, then incubate with the corresponding secondary antibody for 1 h, then rinse with TBST three times before exposure.After collecting the cells, add the appropriate amount of Trizol reagent, mix well, add 200 µL of chloroform, mix well and place at 4 °C for 15 min, then centrifuge at 12,000 rpm at 4 °C for 15 min, collect 500 µL of supernatant and add the same amount of isopropyl alcohol, mix well and stand at 4 °C for 10 min, then centrifuge at 12,000 rpm at 4 °C for 10 min, discard the supernatant, add 1 mL of 70% absolute ethanol, after shaking, centrifuge at 7500 rpm at 4 °C for 5 min, discard the supernatant and dry, Then add 20 μL of enzyme-free water, measure the concentration and place it at −80 °C for subsequent use.cDNA reverse transcription uses Thermo RevertAid First Strand cDNA Synthesis Kit, and all steps are performed strictly in accordance with the corresponding instructions. For qPCR, mix according to the following recipe: 10 µL FastStart Universal SYBR Green Master (Rox), 2 µL cDNA, 1 µL preprimer, 1 µL post primer, 6 µL enzyme-free water. After mixing uniformly, add it to a 96-well plate for qPCR, and then use the corresponding machine for qPCR detection.RIP assay was performed using Magna RIP kit, all detail steps were done according to the corresponding manuscripts. After RNA was extracted from beads, the following step should be cDNA synthesis and PCR or qPCR.Co-IP assay was performed using Thermo Pierce Classic Magnetic IP/Co-IP Kit. all detail steps were done according to the corresponding manuscripts. After protein was extracted from beads, western blot was used as the detection method.It is important to point out that all the antibodies used here should be suitable for RIP or co-IP, otherwise it may lead to failure to obtain correct results.RNA pull-down experiment consists of five parts, plasmid digestion, in vitro transcription, 3’-end biotinylation labeling, RNA pulldown, and western blot detection. The plasmid containing PCBP1-AS1 sequence was generated and digested by Sangon Biotech (Sangon Biotech (Shanghai)Co., Ltd), T7 promoter was added to facilitate our subsequent in vitro transcription. In vitro transcription was performed with MEGAscript™ T7 Transcription Kit, 3’ end biotinylation was done by Pierce RNA 3’ End Biotinylation Kit, RNA pull-down assay was performed by Pierce Magnetic RNA-Protein Pull-Down Kit. All steps above followed strictly to the corresponding manuscript. After protein was extracted, western blot was followed as a detection method.EnzR cells, respectively. The two parts of the experiment have different purposes. The C4-2 cell-related animal experiment aims to observe the effect of targeting PCBP1-AS1 on tumor growth, while the C4-2EnzR-related animal experiments focused on the effect of targeting PCBP1-AS1 on the sensitivity of tumor enzalutamide.This study contains two parts of animal experiments, using C4-2 cells and C4-27 cells. After a week, tumors were formed. The tumor size was measured every other day, and adeno-associated virus (AAV) was injected into the tumor on the 14th day—five injected with AAV targeting PCBP1-AS1 and five with AAV containing invalid sequences—continue to cultivate the mice, and count the tumor volume. After 1 week, the mice were euthanized under anesthesia, and then the tumors were taken out and photographed and immersed in formalin for short-term preservation, and then made into wax blocks for subsequent experiments  and injected with AAV-PCBP1-AS1 or AAV-Scramble, keep feeding under enzalutamide condition for 2 weeks, mice were euthanized by the same method, Take out the tumor and take pictures, and save the tumor in formalin for a short time for the subsequent experiments (Supplementary Fig. As for enzalutamide-related in vivo experiments, C4-2T test, and the significance between multiple groups is calculated by ANOVA. The significance of Kaplan–Meier survival analysis was calculated using the log-rank test. All codes can be traced, please contact zhangboya_0722@163.com.The bioinformatics analysis in this study was performed using R-Version 4.0.0, and the R packages used were limma, edgeR, ggplot2, survminer, and Survival. In terms of statistical analysis, mean + /− SD is used, the significance between the two groups is performed by For the TMA experiments in Fig. P<0.05, **P<0.01, ***P<0.001, ****P<0.0001.Significance: *Reproducability ChecklistSupplementary figure 1Supplementary table 1


Women with breast tumors with higher expression of AR are in general known to have better survival outcomes while a high AR/ER ratio is associated with poor outcomes in hormone receptor positive breast cancers mostly in post menopausal women. We have evaluated the AR/ER ratio in the context of circulating androgens specifically in patients younger than 50 years most of whom are pre-menopausal and hence have a high estrogenic hormonal milieu.Tumor samples from patients 50 years or younger at first diagnosis were chosen from a larger cohort of 270 patients with median follow-up of 72 months. Expression levels of ER and AR proteins were detected by immunohistochemistry (IHC) and the transcript levels by quantitative PCR. Ciculating levels of total testosterone were estimated from serum samples. A ratio of AR/ER was derived using the transcript levels, and tumors were dichotomized into high and low ratio groups based on the third quartile value. Survival and the prognostic significance of the ratio was compared between the low and high ratio groups in all tumors and also within ER positive tumors. Results were further validated in external datasets (TCGA and METABRIC).Eighty-eight (32%) patients were ≤50 years, with 22 having high AR/ER ratio calculated using the transcript levels. Circulating levels of total testosterone were higher in women whose tumors had a high AR/ER ratio (p = 0.02). Tumors with high AR/ER ratio had significantly poorer disease-free survival than those with low AR/ER ratio [HR-2.6 (95% CI-1.02–6.59) p = 0.04]. Evaluation of tumors with high AR/ER ratio within ER positive tumors alone reconfirmed the prognostic relevance of the high AR/ER ratio with a significant hazard ratio of 4.6 . Similar trends were observed in the TCGA and METABRIC dataset.Our data in pre-menopausal women with breast cancer suggest that it is not merely the presence or absence of AR expression but the relative activity of ER, as well as the hormonal milieu of the patient that determine clinical outcomes, indicating that both context and interactions ultimately influence tumor behavior. Breast cancer in the young is more commonly associated with aggressive features and poorer clinical outcomes when compared to that of an older age group . AlthougCirculating androgens are detected during all ages in adult women and hence thought to have biological roles . MultiplIn vitro studies have demonstrated that AR might decrease ER transcriptional activity probably by competing to the same binding sites as ER in breast tumors , and HER2 was obtained from their clinical records. Treatment information was obtained from clinical records of patients during follow-up. Endocrine therapy was recorded as tamoxifen or aromatase inhibitor, and chemotherapy regimens were noted for intake of anthracyclines or taxanes. Information on trastuzumab was recorded in HER2 positive patients whenever received. Formalin fixed paraffin embedded (FFPE) blocks from tumor tissue having more than 50% of the area of representative tumor were selected for the study.XT staining system . Briefly, 5 μm thick sections were fixed in hot air oven at 60°C for 60 min and loaded on to an IHC staining machine. De-paraffinization was performed using EZ Prep solution (Proprietary-Ventana reagent), and antigen retrieval was done using Cell Conditioning solution 1 (CC1) for 60 min. Primary antibody for AR  was added manually and incubated for 32 min at room temperature. Optiview DAB Detection Kit  was used to visualize the signal, using DAB (3–3′diaminobenzidine) as the chromogen. Further, the sections were automatically counterstained with hematoxylin II  for 12 min. The slides were removed from the autostainer, washed in de-ionized water, dehydrated in graded ethanol, cleared in xylene, and examined by microscopy. Appropriate positive and negative controls were run for each batch. Two pathologists scored the staining for AR protein independently and arrived at a final score. Nuclear staining in more >1% of tumor cells was considered as positive.Immunohistochemistry for AR was done on each of the tumor sections as per standard protocol using the Ventana BenchmarkTotal RNA was extracted using the Tri Reagent protocol according to manufacturer’s instructions (Sigma Aldrich # T9424) from two 20 µm sections from the selected tumor block. Briefly, tumor block was deparaffinized using heat, and then subjected to overnight digestion using proteinase K (Qiagen #19133). Quantitation of the RNA was done using the Qubit RNA BR (Broad-Range) Assay Kit (Invitrogen # Q10210) on a Qubit 2.0 Fluorometer (Invitrogen #Q32866). Then 500 ng of total RNA was reverse transcribed to cDNA using high capacity cDNA conversion kit from Thermofisher scientific (Cat # 4322171) as per manufacturer’s instruction.AR and ESR1 genes using primer 3 plus software and further validated on ensemble genome browser, NCBI blast and UCSC genome browser. The primers were synthesized by Juniper Life Sciences, Bangalore, India. The details of the primer sequences are given in the ® Green on the LightCycler® 480 II (Roche Diagnostics). Pre-incubation and initial denaturation of the template cDNA were performed at 95°C for 10 min, followed by amplification for 45 cycles at 95°C for 15 s and 60°C for 1 min. Cycles of threshold (Ct) values for the test genes were normalized to the mean Ct values of the three reference genes—ACTB, RPLP0, and PUM1 for each tumor sample which was normalized for varying abundance of transcripts. Relative normalized expression of test genes was calculated by ΔCT method. The methods used for nucleic acid extraction, quantitative PCR (qPCR), and selection of housekeeping genes (HKGs) and the quality control criteria for inclusion of samples in the analysis have been described in detail in our previous publication  & i2000 (Immunoassay) instrument. In brief, the serum sample with a minimum volume of 300 µl was loaded onto the instrument. The sample was then transferred into multiple compartments where it is mixed, incubated, and washed. In the subsequent steps, the conjugate, pre-trigger and trigger solutions were added. The chemiluminescence emission was measured to determine the quantity of total testosterone in the serum sample. The result was calculated using a four parametric logistic curve fit data reduction method to generate a calibration curve.Descriptive analysis was done to evaluate the cohort characteristics and distribution of the high and low AR/ER ratio groups. Difference in the clinical variables between high and low ratio groups was tested by independent Student’s t-test or Mann–Whitney U test for continuous variables, and chi-square test was done for categorical variables. Concordance between the AR transcript and protein was estimated by receiver operating characteristic (ROC) curve analysis. Kaplan–Meier survival curves and log rank tests were used to compare the disease-free and breast cancer specific survival between the high and low AR/ER ratio groups. Disease free survival (DFS) and breast cancer specific survival (BCSS) were calculated as the time from the date of first diagnosis to the time when a local or distant recurrence occurred and death due to disease, respectively. Patients with no event or had death due to non-breast cancer related causes were right censored. The prognostic importance of high AR/ER ratio in comparison to other clinicopathological characteristics was validated by both univariate and multivariate cox-proportional hazard analyses. All tests were two tailed, and P-value <0.05 was considered statistically significant. All statistical analyses were done on statistical software XLSTAT version 2019.4.2 and SPSS software version 20 .A total of 270 patients were included in the study with a median age at first diagnosis of 56.2 years. Nearly 60% of the tumors were associated with spread to the regional lymph-nodes and half of women were at clinical stage 2 and a third stage 3. Less than 10% of the tumors were grade 1 with approximately half being grade 2; 68% were estrogen receptor positive, and 19% were HER2 positive. Clinical variables are shown in Most of the patients (>95%) were treated with stage appropriate endocrine and chemotherapy as standard of care except those with stage IV disease who died due to disease before completion of therapy. Of ER positive patients 93% (50/54) received endocrine therapy and received stage appropriate chemotherapy as well. Similarly, in ER negative patients, more than 90% of patients received stage appropriate chemotherapy and one had defaulted. Only 15% (3/20) of the HER2 positive patients received trastuzumab while 95% of them received anthracycline and taxane based regimens as intensive chemotherapy.Among the 270 patients, 88 women were less than or equal to 50 years at first diagnosis, and the median age of this subset was 43.1 years. In this subset, 60% of the tumors were lymph node positive, and nearly half of the tumors belonged to stage II. Ninety-five percent of the tumors were equally distributed between grades II and III. Sixty percent of the tumors were ER positive. Eighty percent of these patients were pre-menopausal (70/88), and the remainder had been diagnosed with breast cancer on average within 3 years of menopause. No significant difference in any of the clinical characteristics was observed when this subgroup was compared to the entire cohort Table 1.Immunohistochemistry for AR could be successfully evaluated in 189 of the 275 tumors. Eighty six tumors were not evaluated either due to insufficient tissue or tumor content. An additional 12 tumors were excluded due to poor tissue preservation, and hence the final evaluation included only 177 tumors from 173 women. There were 59/173 women (34%) less than 50 years, and 114/173 women (66%) were >50 years of age.vs 45% (37/82) in ≤50 years vs >50 years respectively]. Overall, only 30% (53/177) of the tumors were dual positive for both ER and AR. Of AR positive tumors, 80% were ER positive in all samples, and similar results were seen in both age groups.Overall, 66/177 (37%) tumors had nuclear staining for AR. There was no difference in the distribution of AR protein by age groups (34% (20/59) in ≤50 and 39% (46/118) in >50 years age group). Of the 177 tumors, 120 were ER positive by IHC; 53/120 of these ER positive tumors were AR positive as well, and this proportion did not differ between the age groups  awarded to JSP. Patient recruitment and follow-up activities was supported by philanthropic funding received from Nadathur Estates Private Ltd., Bangalore, India and from Bagaria Education Trust, Bangalore, India. The authors declare that this study received funding from Nadathur Estates Private Ltd., Bangalore, India and Bagaria Education Trust, Bangalore, India for patient recruitment and follow-up activities. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication.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.


The applications and electronic devices used and the measurement instruments used were described. The use of AR made it easier for students to acquire skills, especially in courses with a high component of three-dimensional visualization, and positively influenced various aspects of the learning process such as motivation, satisfaction or autonomous learning. As an educational technological tool applied to higher education in health sciences, AR improves the teaching-learning process by influencing it in a multidimensional way.The objective of this study was to investigate the usability of the augmented reality (AR) in higher education in the area of health sciences to describe what type of interventions have been developed, their impact on various psychopedagogical aspects of the students as well as the main advantages, disadvantages and challenges in incorporating AR in the teaching-learning process. A systematic review was carried out in the CINAHL, PsycINFO, MEDLINE, Web of Science databases and the Google Scholar search engine. The search was limited to original research articles written in English, Spanish or Portuguese since 2014. The quality of the selected articles ( In recent decades, higher education has undergone an important methodological change because the curricular design is increasingly focused on the student. The use of information and communication technologies (ICT) in teaching-learning processes allows the teacher to facilitate student learning by adapting the contents and methodology to different rhythms and interests of the students . The lasAR was defined in very different ways throughout its short existence, although the most widespread definition states that AR consists of a mixed environment that integrates digital information in a real environment . Di SeriThe use of AR in education is still in the early stages ,4,5,6, dThe use of AR in higher education in the area of health sciences can contribute to improve the acquisition of skills, providing the student with a more authentic learning and a more personalized learning experience . LikewisOur research presents the state-of-the-art of AR in health science higher education, describing the scholarly values of this technology. To facilitate decision-making by health science educators on specific didactic aspects in this field, a systematic review of the literature has been carried out with the aim of locating and integrating the main results of studies on this topic.(1)What kind of augmented reality interventions are used in health sciences higher education?(2)What impact does the use of augmented reality have on the educational outcomes and skills of these students?(3)What are the main advantages, disadvantages and challenges of this technology during the teaching-learning process?Specifically, the objective of this systematic review was to identify, evaluate and summarize the evidence conducted using augmented reality with health sciences students in higher education. This mixed method review aimed to answer the following questions:This review employed a data-based convergent synthesis design, a type of mixed method systematic review synthesizing evidence derived from quantitative and qualitative studies . The PreIn order to explain the search process in detail, it is indicated by the initials what each author (see the first page for the full name) did to ensure the systematization of this step of the review, as well as the following steps. A systematic search approach of specific health and social science databases was independently performed by the authors CR and JCF from March 2020 to May 2020. These were CINAHL, PsycINFO, MEDLINE and Web of Science. A Google Scholar search was also performed. One of the authors’ expert knowledge (JCF) and previous articles were used to determine and refine the search terms and controlled vocabulary, when available. Keywords were searched in titles and abstracts, as well as in other fields when appropriate  were assessed by the same authors. Any discrepancies or doubts during all the screening process were resolved by consensus within the other authors (JCF and RR). This stage led to 19 articles, after excluding 61 studies. Following the eligibility criteria, titles and abstracts were screened independently (CR & AM). For the stage two in the screening, the potentially relevant articles with full texts  articles published in peer-reviewed journals and (2) empirical studies that reported the use of AR in health science studies. Exclusion criteria were the following: (1) describe AR in areas of knowledge other than health sciences, (2) report AR at other educational levels other than higher education, (3) the technology used to support the teaching-learning process was not AR, (4) the objective of the study was not focused on AR, and (5) unable to source the full text paper reporting the original study.The data extraction was completed by one author (CR) while other author independently checked the findings (AM). Once the data was extracted in text form, an ad hoc table was developed through consensus to categorize the data following the review aims. This abstraction was completed by the same authors (CR and AM) and included: author(s), year of publication, country, academic degree, academic year, course and sample size, aims and measuring instruments, results and MMAT rating.n = 13) and mixed method studies (n = 6) were subjected to a convergent thematic and narrative synthesis, in line with Hong et al. (2017) [The extracted data of quantitative studies n =  and mixe. (2017) .Quality appraisal was conducted independently by authors and final assessment for quality and the risk of bias was the product of the consensus. Systematic reviews with PRISMA require a critical appraisal of the included studies . The MixThe studies generally met the criteria of MMAT-checklist. Though, they did not consider some aspects: Descriptive quantitative studies mostly fail or did not allow responding to the MMAT 4.5 criterion “Is the statistical analysis appropriate to answer the research question?”. In the case of quantitative randomized controlled trials, they did not meet the MMAT 2.4 criterion “Are outcome assessors blinded to the intervention provided?”. In the analysis of the methodological quality of the quantitative non-randomized studies, it is not possible to respond to the MMAT 3.4 criterion “Are the confounders accounted for in the design and analysis?”. Lastly, two mixed-methods studies met all MMAT criteria, but the rest did not provide data to respond to the MMAT 5.3 criterion “Are the outputs of the integration of qualitative and quantitative components adequately interpreted?” (see n = 13) met 75–100% of the MMAT checklist, representing high quality. 26.4% of the articles (n = 5) met 50–75% of the evaluated criteria, representing moderate quality. 5.4% of the articles (n = 1) met less than 50% of the evaluated criteria, representing low quality , followed by Spain (n = 2), Netherlands (n = 2), Germany (n = 2) or Australia (n = 2). The remaining studies were conducted in UK, Denmark, Portugal, South Africa, Turkey, Brazil and Chile. No study was performed in Asia. Quantitative studies (n = 13) included questionnaires and surveys, while mixed-method studies (n = 6) utilized questionnaires and interviews about opinions or participants feedback about the experience. Study designs included randomized trials (n = 4), non-randomized trials (n = 4), descriptive studies (n = 5) and mixed method studies (n = 6). Sample sizes ranged from 4 to 880 students (see The current review included 19 studies. Most of them took place in USA (ents see .n = 12) followed by Nursing (n = 3). The subjects in which AR was predominantly implemented were Human Anatomy (n = 12) followed by practical classes or Clinical Simulations (n = 3). Most of the studies were carried out with first (n = 7) or second-year students (n = 2). See The degree in which the most AR experiences were developed was Medicine (n = 19) were synthesized and collated into three main themes which were:The findings from the studies , and pedagogical usability aims to support the learning process; both terms should not be considered independently ,23. TakiIn the development of skills oriented to decision-making and performance of practical procedures, especially in inexperienced individuals .In the creation of more realistic interactive learning spaces that promote and facilitate autonomous and collaborative learning, facilitating the acquisition of the skills provided in the study plans ,12,25,26In making learning more flexible, by allowing access to content at any time regardless of location .In the teaching-learning of human anatomy, since the three-dimensional vision provided by AR facilitates spatial understanding, and, therefore, the acquisition of knowledge .Despite the numerous alternatives made possible by the use of AR as a didactic tool in Higher Education in Health Sciences, it is not implemented in a massive way . Neverthn = 13) specified the software used to develop virtual content. The most used was Unity in combination with Vuforia (n = 6), showing advantages over others for its ease of use, its high graphic quality and that allows the creation of multiplatform applications. Applications such as Metaio Creator or Aurasma used by some authors [n = 2) use AR mobile applications not developed specifically for their research, but instead were free applications, such as Anatomy 4D, that allowed students to interact with clipart images of the human body through mobile devices [Dynamic Anatomy, available for smartglasses (Hololens), was developed expressly for the investigation of Bogomolova et al. (2020) and facilitates learning the dynamic anatomy of the ankle joint through its free access [Most selected articles , followed by smartglasses (n = 5) and large monitors (n = 3). In one of the articles no data was indicated on the applications and devices used. Regarding AR levels, most articles (n = 11) used markerless technologies (image recognition).Various data collection instruments were used in the articles included in this systematic review. These were administered before, after or before and after the AR experiences. The instruments measured different parameters, such as the perception of the students with the AR experience, the degree of motivation that AR generates in the students, the cognitive load used in the learning process or the degree of acceptance of AR-based technology.Specifically, to measure the perception of students with the AR experience, Agudelo et al. (2019) administered an ad hoc survey to the students with three dimensions: implementation and contributions to training, collaborative learning and motivation with the innovative methodology . The valn = 10). Various authors [Student motivation is measured in more than 50% of the studies analyzed . In seven of them, students who experimented with AR showed a higher level of motivation compared to those who used other methodologies [Student motivation and involvement towards learning was analyzed in several studies Academic performancen = 6) measured the academic performance previously and after the AR experience of the students to find out the influence of AR on learning outcomes. In fiveall of them, students that used AR-based methodology obtained significantly higher scores on post-intervention knowledge tests [Several studies Acquisition of clinical competenciesAR improved clinical decision-making skills in the treatment of chronic wounds in Nursing students . In the (c)Acquisition of cognitive skillsAgudelo et al. (2019) underlined the excellent assessment that Phonoaudiology students make on the use of a methodology based on AR, contributing to the construction of learning and collaborative work . These rOnly two studies measured the cognitive load used by students in the acquisition of knowledge ,34. In bRegarding spatial visual skills, two articles showed that the stereoscopic effect provided by AR improves spatial understanding. This occurred especially in those students with low visual spatial capacity, making it a useful tool to facilitate the comprehension of anatomical structures ,37.There are no studies that have focused on the benefits of training experiences using AR beyond the training programmes, that is, in the actual development of health sciences professionals. However, some studies allow us to infer the specific benefits of undertaking such experiences by comparing participants included in AR training programmes with control groups, that is, using other learning methodologies. In this sense, the use of AR in the teaching-learning processes has been pointed to provide multiple benefits, such as a higher performance in the diagnosis of chronic wounds , a more The authors of the articles selected in this research detailed multiple advantages and disadvantages of AR as a teaching methodology. These aspects could be considered when planning how AR will be used as an element to support the teaching-learning process.Among the pros can be highlighted that AR enhancement the real world because allows the incorporation of virtual objects into a real environment, which allows to enrich reality, not replace it . ThroughRegarding the cons, the difficulty in using and handling some devices can be underlined. Participants in the experience of Bogomolova et al. (2020), used smart glasses to visualize the AR teaching content. They pointed out difficulties in adjusting the glasses, instability of the projected image and the need to keep the head still, among others . NørgårdAR is a new technology little implemented in education and its incorporation as a teaching technology tool is recent, so research on this topic is novel but scarce . In addiSometimes AR has a high cost of implementation. Bogomolova et al. (2020) used the highest level of AR, augmented vision, with smartglasses that provide stereoscopic 3D vision. They identified as a disadvantage the high cost of the development of the experience, which, on the other hand, facilitates the learning of students with low spatial visual skills, an improvement compared to other cheaper AR levels  . In addiThe aims of the study were to identify and summarize the AR interventions used in higher education in health sciences, the impact of AR on educational outcomes and skills, as well as the main advantages, disadvantages, and challenges during the teaching-learning process.n = 10) of the articles included in this systematic review, smartphones or tablets were mostly used to interact with AR content. Despite the boom experienced in recent years, the use of AR as an innovative technological educational tool is still quite limited, despite the great advantages that have been found. This is mainly due to the reluctance of teachers, the lack of training and means to generate 3D content. Perhaps this is due to the scarcity of research that demonstrates the efficacy and effectiveness of this technology, since most of the studies analyzed have a small sample size in a single institution, which makes it difficult for the data to be generalizable.The use of AR in health sciences degrees has increased in the last few years. This has been largely due to the massive use of mobile electronic devices by students, which greatly facilitates the implementation of this educational tool in the classroom ,30,40. In = 13). Evidence shows that the curricular competences of this course are clearly favored by AR, especially in students with low visual spatial abilities [Most of the research included in this review on the usefulness of AR was developed in the field of Anatomy , in most of them (n = 8) AR significantly increased both. In very few (n = 2), no significant differences were found associated to the use of an AR-based teaching methodology. In the case of Henssen et al. (2019) these findings could be due to the fact that AR is compared with the use of cadaveric material, which is considered the gold standard in the study of anatomy [In relation to motivational aspects, they have been extensively studied in selected articles. Of the total number of articles that evaluate motivation and involvement  report on the usefulness of this technology to improve the skills of students and professionals in the performance of a medical technique consisting of the canalization of a central venous catheter . It was This review provides information on the most used applications for the use of AR, which might help with decision-making and instructional planning in Health Sciences. Even though there are different AR software, some of them are no longer available. This short obsolescence could difficult a long-term use and contribute to teaching overload when having to redesign the didactic materials in a new application.The use of AR has increased in the last decade. This systematic review has been done through a multidisciplinary search strategy in three languages, synthesizing and interpreting the findings of the last few years. Thus, it provides information for future research and implementation of educational innovation.Regarding limitations, the most frequent was the small sample size, which requires caution when interpreting the results and drawing conclusions. In addition, negative results may have been missed due to publication bias. Therefore, more studies are needed to address this issue with more representative and multicenter samples. In this way, it could be studied in greater depth to what extent AR modifies academic performance in different educational contexts at the international level. In the same sense, no studies have tried to contrast the long-term effects in participants’ professional performance or benefits for healthcare units/patients. Due to the nature of this review  no prior protocol was recorded. More research with standardized instruments and protocols are necessary to perform meta-analysis. Considering the heterogeneity regarding methodologies of the studies, a meta-analysis could not be performed.According to this systematic review, AR used as an educational technological tool in university studies in Health Sciences improves the teaching-learning process by influencing it in a multidimensional way.The use of AR in higher education in the field of Health Sciences reduces the cognitive load and increases the motivation and satisfaction of the students. Its use as a learning support tool also improves spatial understanding and promotes autonomous learning, in line with the guidelines of the European Higher Education Area. Given that AR provides clinical simulation environments with greater realism, we can conclude that the use of this technology in Health Sciences is especially useful in those courses with a large component of 3D vision during the teaching-learning process. However, guidance on how to make effective use of AR and more developers that support the teaching process are needed, together with the promotion of its use through, for example, competitive projects or awareness of higher education institutions towards this technology.Thanks to the massive use of smartphones among the university community and the free availability of some applications, the teaching use of this technology is being democratized with multiple advantages in the teaching-learning processes.


In Saudi Arabia, motor-vehicle crashes (MVC) are the leading cause of disability-adjusted life years (DALYs). There is limited information locally on the magnitude and need for rehabilitation following MVC. This study examined the prevalence of MVC patients requiring long-term rehabilitation and the epidemiology of associated injuries.A retrospective study was conducted at four hospitals of the National Guard Hospitals Affairs from January 2016 to March 2019. The study used data from an institutional trauma registry of all MVC admissions. Chi-square tests, bivariate and multivariate analyses were conducted to compare patients requiring long-term and short-term rehabilitation.The study included 506 patients. The study population was relatively young, with an average age was 32.8 ± 15.5 years, and the majority were males. Over two-thirds (71.3%) of patients required long-term rehabilitation. Half the patients sustained multiple fractures, and 17.0% sustained traumatic brain injuries. Overall, 53.1 and 61.8% of patients required occupational and physiotherapy, respectively. Those admitted to the intensive care unit were four times more likely to need long-term rehabilitation.We found a significant burden of long-term rehabilitation following MVC. Patients were relatively young, thus posing a significant burden on future healthcare utilization. Policymakers should use these findings to guide primary, secondary, and tertiary prevention to improve health outcomes. Motor-vehicle crashes (MVC) are an alarming issue globally . AccordiMVCs are one of the leading causes of injury-related disability, accounting for one-fourth of all injury-related disabilities in the United States . Many MVIn Saudi Arabia, MVCs are the leading cause of injuries, responsible for 52% of all injuries . This fiDisabilities associated with MVCs can be defined as any reduction in levels of functioning due to injury . ExampleWhile the burden is high, data on the disabilities and burden of nonfatal MVC is limited. A review of the literature on MVC found that the most common injuries were head, neck, and limbs . These iRehabilitation services can include physical therapy and occupational therapy . PatientOne of the common consequences of MVC is polytrauma, defined as “the Abbreviated Injury Scale (AIS) ≥ 3 for at least two different body regions” . CompareThere is limited information on the need for rehabilitation following MVC in Saudi Arabia. It is imperative to understand the current status to assess future needs for rehabilitation services locally. We aim to determine the prevalence of patients that require long-term rehabilitation. This study will provide a basis for the demand for rehabilitation services in Saudi Arabia by answering this research question. Furthermore, it will provide a basis to galvanize prevention efforts to promote traffic safety and ultimately improve population health.This was a retrospective study conducted at four National Guard Hospitals Affairs (NGHA) hospitals in Saudi Arabia from January 2016 to March 2019. All patients meeting the inclusion criteria were identified. Data captured included four locations: King Abdulaziz Medical City in Riyadh with 394 patients, King Abdulaziz Medical City in Jeddah total number 63, King Abdulaziz Hospital in Al-Ahsa with 39 patients, Al-Imam Abdulrahman bin Faisal Hospital in Dammam included ten patients. Data were ascertained from the trauma registry provided comprehensive information on trauma patients who were admitted to the hospital for at least one day following MVC during the study period.Next, rehabilitation data were ascertained from the electronic medical records. The study population comprised all patients ≥16 years old who were admitted to KAMC due to MVC between 2016 and 2019. A trained research coordinator reviewed all admitted patients with MVC and verified patients were actually injured in MVC and hospitalized. Patients treated in the ED then immediately discharged were excluded from the study.Patients were classified as requiring long-term rehabilitation if they were diagnosed with one of the following injuries: spinal cord injury, amputation, traumatic brain injury, lower extremity fracture, multiple fractures, open fracture or polytrauma. This was based on two physicians’ expert opinions and consensus (an orthopedic surgeon and a rehabilitation physiatrist). In addition, long-term rehabilitation users included those discharged and seeking care in outpatient clinics for at least three months. Patients who required short-term rehabilitation were those who sought rehabilitation services for three months or less.The trauma registry includes demographics, injury type and cause, severity, LOS, and discharge status. To complement information not available in the registry, research coordinators used a pre-designed data collection sheet that includes access to rehabilitation, rehabilitation length of inpatient stay, description of patient’s disability, date of discharge, and discharge status or death. A patient was considered disabled if they suffered from a long-term impairment of function . This inPatients were classified based on the site and the severity of the injury. The injuries were classified using the AIS in all five major body regions into minor (1 point), up to severe or maximal (untreatable) (6 points) . Only thp = 0.5, the precision of 5% of the true value. The minimum required sample size is 385 patients to estimate the prevalence [The trauma registry in KAMC includes over 20,000 patients. In this study, the sample size was calculated using 95% as a confidence interval, 5% margin of error, and assuming evalence . We inclp-value 0.3 and retained variables at a p-value of 0.05. The following variables were entered into the initial model: age, gender, BMI, mechanism of injury, body region, surgery, and ICU admission. The model included the following variables: ICU admission (“no” as the reference group), surgery (“no” as the reference group), and affected body region . Statistical analyses were performed using STATA version 15.0 software, and a p-value of < 0.05 was declared as statistically significant.Descriptive statistics were carried out in the form of mean, standard deviation (SD), and frequencies. The outcome is the prevalence of MVC patients who require long-term rehabilitation. It was defined as the proportion of patients with long-term rehabilitation as part of the overall admitted MVC patients. We also estimated the prevalence of patients who received interdisciplinary rehabilitation, defined as receiving all the services including physiotherapy, occupational therapy, psychiatric treatment, and social service support. For inferential statistics, chi-square tests were applied to compare long-term and short-term rehabilitation patients. Continuous variables, including ISS score and LOS, were compared using Student’s t-test. In addition, multivariate logistic regression techniques were used to model the probability of long-term rehabilitation with associated variables. We used multivariate forward selection regression with entry criteria of at least a A total of 506 medical records were retrieved from the trauma registry upon meeting the inclusion criteria. The mean (SD) age of patients was 32.8 15.5) years, and a majority were males (83.3%). Patients were relatively young  of the injured population utilized any rehabilitation services. More than half (53.1%) utilized occupational therapy, and 61.9% accessed physiotherapy treatments, while 168 33.2%) used neither service. Among patients, 4% died following their injuries. Multiple fracture disabilities were the most common among patient disabilities (50.6%), followed by a single fracture (33.4%) and polytrauma  Table Patients who needed long-term rehabilitation sustained more severe injuries than those who required short-term rehabilitation. This was represented by a significantly higher ISS 13.45) and lower GCS scores than in short-term rehabilitation. Longer LOS in the ICU was associated with patients’ rehabilitation status 5.47 (±10.86) for long-term rehabilitation vs. 1.13 (±3.24) days for the short-term rehabilitation group . These findings underline the burden of MVC on population health. Major investment in primary prevention by increasing traffic safety is desperately needed to address this burden. In addition, there is a need to improve and expand rehabilitative care services to meet the high demand represented by the increased demand due to injuries.Reckless driving behaviors may explain the severity of MVC injuries found in our study. Local studies on MVC trends have shown that unsafe driving behaviors such as speeding, low seatbelt compliance, among other traffic law violations, are frequent contributors to the high incidence of MVC injuries . EnforceThe majority of patients admitted for MVC within the study timeframe were young and male. This might be because women were not legally permitted to drive in Saudi Arabia before 2018 . MoreoveFurthermore, we found that motor-vehicle drivers and passengers are significantly more likely to need rehabilitation than motorcyclists and pedestrians. Comparatively, this was not the case in other countries. A study on the prevalence of MVC-related disability in Iran found that pedestrians and motorcyclists were 1.7 and 1.1 times more likely to become disabled, respectively . One potHead injuries pose a major threat to patients’ outcomes. A study estimated that head and neck injuries were responsible for 34% of MVC fatalities . SignifiRecovery time is a major concern for patients and their families. It is usually difficult for healthcare providers to predict recovery time due to various influencing factors. The impact ISS and GCS play in need of long-term rehabilitation could guide clinicians’ expectations while delivering care and communicating with MVC patients. Considering the magnitude and prevalence of MVC in Saudi Arabia, access to rehabilitation must be improved, especially as motor vehicles remain the dominant mode of transportation . MarkedlInvestment in improving access and capacities of rehabilitation services is a necessary measure towards lowering the burden of MVC injuries, a primary objective of the Saudi Vision 2030. An issue to be considered is the limited number of specialized rehabilitation centers. Only two major specialized rehabilitation centers exist in the Riyadh region, serving a population exceeding 8 million individuals . LimitedThis study offers a glance into how rehabilitation services are utilized by MVC patients and the epidemiology of MVC injuries locally. However, it is not without limitations. Since data were retrieved from one health system, we cannot say the findings are generalizable to the whole population. Another limitation is the retrospective nature of the study. Therefore, causality cannot be determined.Moreover, we did not collect data about patients’ cognitive, behavioral and emotional complications or barriers to receiving rehabilitation services. A potential area for future research would be to explore rehabilitation access and capacity for MVC patients in the Kingdom. We recommend that more research in planning and executing primary preventative measures against MVC should be invested to reduce the burden of MVC.The study found a significant burden of long-term rehabilitation following MVC. Patients were relatively young and will pose a major burden on future healthcare utilization and population health. Policymakers can use these findings to guide primary, secondary, and tertiary prevention to reduce the burden of MVC and improve health outcomes.