The importance and necessity of home-based rehabilitation with professional and systematic interventions should be considered since home-based rehabilitation has been institutionalized as it is more feasible, cost effective, and even safer than in-hospital rehabilitation in most countries—though not in South Korea. In addition, the need for home-based rehabilitation is increasing due to the increasing number of hip fracture patients and limited capacity of acute hospital rehabilitation. Therefore, the purpose of this study was to investigate the awareness, needs, and preferred components of home-based rehabilitation services after discharge for elderly patients with hip fracture surgery in South Korea. A survey of 98 elderly patients who recently underwent hip fracture surgery was performed using a questionnaire. More than 75% of patients agreed on the need for home-based rehabilitation, even though most had never heard of it. The reason for the need for home-based rehabilitation was that it is possible to receive continuously ongoing treatment (53.0%), and it alleviates the inconvenience of visiting hospitals (27.7%). In addition to this, about 15.7% of patients responded that they could achieve mental comfort. In other words, patients can recover in an emotionally stable environment without the psychological anxiety they might experience in hospital. Thus, in order to maximize the effectiveness of home-based rehabilitation and provide comprehensive guidance including exercise, education, motivational support, and environmental modification, to patients undergoing hip fracture surgery, the component of the rehabilitation program must be developed based upon rehabilitation experts’ knowledge and patients’ value. Additionally, corresponding policies should be established. Hip fracture is a serious injury that requires immediate medical care, especially among older people. Most hip fractures occur in adults aged 65 years and older . The incAccording to the World Health Organization report, among the major musculoskeletal conditions’ burden, hip fracture is the most damaging fracture, being associated with 20% mortality and 50% permanent loss in function . The 1-yAccelerated discharge from hospital and home-based rehabilitation has been institutionalized in most countries, as it is more feasible, cost effective, and safer than in-hospital rehabilitation, but not in certain countries, including South Korea ,19. In STo establish home rehabilitation system which can improve the clinical outcome for older people suffering from hip fracture, evidence-based practice (EBP) would be an option, which is a good life-long problem-solving approach that integrates the best evidence of studies concerned, experts’ opinion and patients’ preference  21]. A . A 21]. The study was conducted according to the guidelines of the Declaration of Helsinki, and approved by the Gachon University Institutional Review Board (1044396-201911-HR-209-02). The purpose of this study and protection of the privacy of participants were fully explained before the survey was conducted. Once the participant agreed to participate in the survey, they signed their informed consent before beginning of the survey.For the evidence-based practice (EBP) that integrates the best evidence of studies concerned, experts’ opinion and patients’ preference, this study was to investigate the awareness, needs, and preferred components of home-based rehabilitation services based on the developed questionnaire by expertise.This study included patients in the study if they met the following inclusion criteria: (1) 65 years or older; (2) admitted to a medical center for a traumatic hip fracture; and (3) underwent surgery to treat hip fracture within 4 months. We excluded people who were unable to perform the survey, such as those who with neurologic disorders who could not perform ADL before the fracture, cognitive impairment or dementia  or who were unable to communicate.We distributed 118 questionnaires to 17 medical centers in South Korea and 100 questionnaires returned, and among them, two questionnaires did not meet the inclusion criteria. We administered a survey to 98 elderly patients post-hip fracture surgery from May to August 2020.We developed the questionnaire used in this study to examine the home-based rehabilitation awareness and needs of patients undergoing hip fracture surgery. A survey entitled, “Questionnaire on the awareness and needs regarding home-based rehabilitation programs for elderly patients after hip fracture surgery in South Korea” was developed. To elaborate the questionnaire, we prepared a draft in accordance with the circumstances of South Korea after several meetings between researchers with reference to previous survey methods ,22. ThenThe content validity of the questionnaire was determined by the panel of experts who conducted the verification of the preliminary evaluation questionnaire. Item-level content validity index (I-CVI) was calculated  using a The final questionnaire involved: (1) the respondents’ basic information; (2) awareness and needs of home-based rehabilitation services; and (3) the importance of the components of home-based rehabilitation services. The questions on “basic information” included gender, age, education, type of residence, primary caregiver, economic status, experience of falling, and walking status before fracture. For the “awareness and needs of home-based rehabilitation services,” we included the elements of awareness of home-based rehabilitation services, the need for such a service, use of this service, and preferred frequency, duration and cost. Questions related to “the importance of the components of home-based rehabilitation services” were rated using a 5-point Likert scale .We conducted the survey between May and August 2020. We distributed the questionnaire to patients who had undergone surgery after hip fracture. The study’s purpose was described on the first page of the questionnaire, and the questionnaire collected during the survey period was used for analysis.The analysis of this study was largely carried out in two aspects: home-based rehabilitation awareness and needs of patients undergoing hip fracture surgery, and the importance of the components of home-based rehabilitation services. Each question contains a variety of other questions, depending on its characteristics, such as a “5-point Likert scale question,” “a single choice item,” “a multiple choice item,” and “yes/no choice item.” For data analysis, frequency analysis was performed according to each item’s characteristics, and the data were calculated as means and standard deviations (SD) for quantitative variables, as well as for the frequency and percentage for categorical variables using IBM SPSS Statistics for Windows . The level of significance was set at α = 0.05.Total of 98 questionnaires were included for statistical analysis. The characteristics of the participants who participated in the survey are shown in The participants were asked to respond on a 5-point Likert scale to determine whether they needed home-based rehabilitation services, as patients with either disabilities or limited ADL. Of the total respondents, 75.6% (strongly agree and agree) agreed for the need for home-based rehabilitation services and only 12.2% of patients disagreed.Regarding the question “Would you like to participate in the service when the home-based rehabilitation service is established?” Eighty-three (84.7%) respondents said “yes” while 13 (13.30%) said “no.” We found that most patients were willing to participate in home-based rehabilitation services when they are launched in South Korea.As for follow-up questions, for patients who responded that they would participate in home-based rehabilitation services, 44 (53.0%) mentioned that “I will likely receive ongoing treatment, even after I am discharged.” Moreover, 23 (27.7%) subjects expressed that there would likely be less of a burden when visiting the hospital, 13 (15.7%) said “I am likely to be mentally comfortable,” and 3 (3.6) asserted “there will likely be less of a burden regarding time.”On the other hand, for patients who said they would not participate in home-based rehabilitation services, eight (61.5%) said they “prefer continued hospitalization or outpatient rehabilitation,” four (30.8%) pointed to a lack of reliability of treatment tools or visiting therapists, and one (7.7%) said, “Medical expenses will likely be higher.”Most respondents—40 people (40.8%)—thought that a proper number of home-based rehabilitation treatment visits was “three times a week”, followed by 23 people (23.5%) who thought “twice a week”. The most appropriate time for treatment was 1 h for 51 patients (52.0%), followed by 30 min for 22 patients (22.4%), and 45 min for 15 patients (15.4%). Among the respondents, 45 people (45.9%) said that the appropriate cost of home-based rehabilitation was “maintaining the current level” (current level: KRW 8170 (USD 7.3) per hour) and 26 people (26.5%) said it should be “less than KRW 5000 (USD 4.4)” .With this study, we aimed to examine the awareness, needs, and preferred components of home-based rehabilitation services for elderly patients having undergone hip fracture surgery after discharge. This survey indicates that establishing a home-based rehabilitation service is necessary for patients having undergone hip fracture surgery.Although only 26.5% of patients said they knew about home-based rehabilitation, more than 75% agreed on the need for it. Our result supports the recent survey of necessity on home visiting physical therapy service in Korea. Kim showed that about 75% patients agreed on the need of home-based rehabilitation . SimilarIn this study, for patients who responded for participating in the home-based rehabilitation service, 44 (53.0%) respondents answered “it is likely to have continuous treatment even after discharge”, and 23 (27.7%) answered “it’s likely to be less burden visiting hospital”. This is similar to previous studies suggesting that home-based rehabilitation can continue treatment even after discharge and reduce discomfort in visiting the hospitals ,24,25. IAs a result, the lack of awareness among patients appears, and the need for active publicity and increased awareness of home-based rehabilitation services are generally high, indicating that the medical system should implement home-based rehabilitation services as soon as possible.The components of rehabilitation programs are important for effective rehabilitation. Since rehabilitation is conducted at home, modifications to the home environment, education, nutrition, and motivational counseling should be included in rehabilitation programs to improve physical functions and emotional status ,27,28. LEvidence-based practice requires integrating the best research evidence with clinical expert judgments, as well as the patient’s values and expectations . Thus, wAs for the patient evaluation score, ambulation exercises were considered the most important, followed by ROM and strengthening exercises. Patients considered pressure ulcer management as the least critical, while the expert group considered this item to be quite vital. Patients and experts disagreed on the “education” category except for positioning education, and modifications of the home environment. This is probably because patients focused more on treatments with immediate effects, while experts thought of integrated treatment from a broader perspective. However, “education” is a crucial element of rehabilitation programs, and a lot of evidence has revealed its effectives ,30,31. EIn addition, legal and institutional support is required which enables patients to continuously receive rehabilitation care in the community after getting discharge from the hospital in order to activate the early discharge of patients who undergo surgery after a hip fracture, . They diIt is expected that the economic burden of medical expenses and time consumed can be reduced by minimizing unnecessary hospital use and transfer to other facilities, and that home-based rehabilitation will be able to meet the needs of hip fracture patients who need rehabilitation after discharge . In partThis study has the following limitations. Even though our selection criteria for participation were very strict, we did not consider the clinical condition  of participants. Since the levels of disability, assistance, or complications after hip fracture surgery greatly vary according to the type of fracture and the type of surgical intervention, the respondent’s thoughts could be interfered with by these their conditions. Additionally, further study should explore the home-rehabilitation service from the caregiver’s point of view of home-based rehabilitation service, since elderly patients with hip fracture surgery need a lot of care,In summary, about 75% elderly patients with hip fracture surgery agreed on the need for home-based rehabilitation and wanted to participated. The component of rehabilitation program must be developed based on rehabilitation experts’ knowledge and patients’ values in order to maximize the effectiveness of home-based rehabilitation and provide comprehensive guidance to patients undergoing hip fracture surgery. Additionally, corresponding policies should be established to actively pursue community health care and private rehabilitation institutions. Hence, home-based rehabilitation will not only meet the needs of elderly patients who undergo hip fracture surgery, but can also provide continuous rehabilitation, even after discharge, in an emotionally stable environment.


After PSM, the AR group demonstrated better OS and RFS rates than the NAR group when tumour size was less than 5 cm, but there was no significant difference in the OS and RFS rates between the two groups when tumour size was equal to or greater than 5 cm. In tumours less than 5 cm in size, AR was the most significant factor associated with OS and RFS. However, this prognostic effect of AR was not demonstrated in tumours with sizes equal to or greater than 5 cm. Conclusion: In patients with HCCs smaller than 5 cm, AR reduced the risk of tumour recurrence and improved OS. In HCCs larger than 5 cm, AR and NAR showed comparable survival outcomes.Background: The relative benefit of anatomical resection (AR) versus non-anatomical resection (NAR) in hepatocellular carcinoma (HCC) remains controversial. This study compared the survival outcomes and recurrence rates of HCCs analysed according to tumour size and the extent of resection. Methods: Consecutive patients with HCC who underwent curative resection at Asan Medical Center between January 1999 and December 2009 were included in this study. We performed propensity score matching (PSM) according to tumour size to compare the survival outcomes between AR and NAR. A total of 986 patients were analysed; 812 and 174 patients underwent AR and NAR, respectively. Results: Before PSM, regardless of tumour size, the AR group demonstrated significantly better 5-year overall survival (OS) and recurrence-free survival (RFS) than the NAR group ( Primary liver cancer, of which 75–85% is constituted by hepatocellular carcinoma (HCC), is the sixth most commonly diagnosed cancer and the fourth leading cause of cancer-related death worldwide ,2. HepatAR involves the systematic removal of hepatic segments delineated by tumour-bearing portal tributaries ,6 and usSeveral studies and meta-analyses have demonstrated the superiority of AR over NAR in terms of long-term survival outcome and recurrence ,9,10,11.Consecutive adult patients (≥18 years) who underwent hepatectomy for HCC at Asan Medical Center, Seoul, Korea, between January 1999 and December 2009 were included in this study. Patients who underwent curative resection were included in this study, whereas patients who underwent non-curative resection for palliative care or R1 and R2 resection, patients with ruptured HCC, patients who underwent re-resection for recurrent HCC, and patients with combined HCC/cholangiocarcinoma in the final pathology were excluded. Patients with vascular invasion on preoperative imaging or pathological results were all included as long as curative resection was achieved. All patients were followed up for at least five years until December 2014. The primary endpoint of this study was overall patient survival. The secondary endpoint was the recurrence of the tumour after curative resection. Patients were divided into two groups according to tumour size .All procedures were performed by a single surgeon with more than 20 years of experience in hepatobiliary surgery and liver transplantation. Anatomical hepatectomy was the primary choice in all patients, and the extent of hepatectomy was individualised according to the estimated remnant liver volume and functional hepatic reservoir. Estimated remnant liver volume was assessed based on computed tomography volumetry, tumour location, and hepatic functional reserve. Hepatic function was assessed with the Child–Turcotte–Pugh (CTP) score and indocyanine green (ICG) retention test. Portal hypertension was evaluated based on platelet count, presence of splenomegaly, and presence of varix on endoscopic findings.Intraoperatively, the extent of the resection in AR was determined by the Glissonean approach, which involved ligation of the tumour-locating Glissonean pedicle. Parenchymal dissection was performed using a Cavitron ultrasonic surgical aspirator  combined with the Kelly clamp-crushing technique and intermittent Pringle manoeuvre. The Pringle manoeuvre was performed for 15 min, followed by 5 min of de-clamping. AR required one Pringle clamping manoeuvre for sufficient transection of one cross-section of the liver parenchyma. For example, one Pringle manoeuvre was required for right hepatectomy, whereas two Pringle manoeuvres were required for right anterior sectionectomy.t-test or Kruskal–Wallis test to compare numerical data. To address the possibility of confounding differences between AR and NAR and selection bias, propensity score matching (PSM) was performed between the AR and NAR groups with a 1:n greedy nearest-neighbour algorithm within specified calliper widths. The matching variables included baseline clinical characteristics such as age, sex, CTP class, primary liver disease, preoperative history of transarterial chemoembolisation (TACE), preoperative levels of the tumour marker alpha-fetoprotein (AFP), platelet count, total bilirubin, and ICG retention rate at 15 min, along with tumour characteristics such as number of tumours, Edmondson–Steiner grade, and macrovascular and microvascular invasion. The adequacy of the matching was described with a standardised mean difference (SMD) value; an SMD < 0.1 was considered balanced. Univariate and multivariate analyses were performed using a Cox proportional hazards regression model. Patient survival (including OS and RFS) was analysed using the Kaplan–Meier method and compared using the log-rank test. Survival comparison between the PS-matched groups was made using Cox proportional hazards regression with robust variance estimator to account for clustering by matched pairs. Differences were considered statistically significant at p < 0.05.Propensity score matching was performed using SAS version 9.4 . All other analyses were performed using R statistical software, version 3.6.3 . Descriptive statistics for numerical variables were recorded as mean ± standard deviation or median with interquartile range, and categorical variables were presented as relative frequencies (percentages). We used the chi-square or Fisher’s exact test to compare categorical data and the Student’s The study was approved by the Institutional Review Board of Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Korea . The same review board waived the requirement for informed consent because of the retrospective nature of the analyses.A total of 986 patients were included in this study, and 812 and 174 patients were categorised into the AR and NAR groups, respectively. The demographics and clinical features of the patients are described in Before PSM, the data demonstrated significant differences in the 5-year OS and RFS rates between the AR and NAR groups A,B.In patients with HCCs smaller than 5 cm, the 5-year OS rates in the AR and NAR groups were 79.5% and 61.8%, respectively. In contrast, in patients with HCCs equal to or larger than 5 cm, the 5-year OS rate in the AR and NAR groups were 55.7% and 47.1%, respectively.In patients with HCCs smaller than 5 cm, the 5-year RFS rates in the AR and NAR groups were 50.2% and 36.6%, respectively. In contrast, in patients with HCCs equal to or larger than 5 cm, the 5-year RFS rates in the AR and NAR groups were 32.9% and 27.5%, respectively. Irrespective of tumour size, the AR group showed significantly better OS and RFS than the NAR group.We performed PSM and reanalysed the above data. In patients with HCCs smaller than 5 cm, the 1-, 3-, and 5-year OS rates of the NAR group were 96.6%, 84.6%, and 62.4%, respectively, whereas those of the AR group were 98.2%, 91.5%, and 78.1%, respectively. In contrast, in patients with HCCs equal to or larger than 5 cm, the 1-, 3-, and 5-year OS rates of the NAR group were 76.5%, 60.8%, and 47.1%, respectively, whereas those of the AR group were 86.5%, 58.1%, and 48.6%, respectively.p = 0.001); the 5-year OS rate in the AR group was significantly better than that in the NAR group (p = 0.644)  B.In patients with HCC smaller than 5 cm, the 1-, 3-, and 5-year RFS rates of the NAR group were 70.9%, 49.6%, and 36.8%, respectively, whereas those in the AR group were 85.3%, 58.0%, and 48.2%, respectively. In contrast, in patients with HCCs equal to or greater than 5 cm, the 1-, 3-, and 5-year RFS rates of the NAR group were 52.9%, 37.3%, and 27.5%, respectively, whereas those in the AR group were 58.8%, 39.2%, and 30.4%, respectively.p = 0.009) (p = 0.472).In patients with HCCs smaller than 5 cm, the 5-year RFS rates of the AR and NAR groups were 48.2% and 36.8%, respectively  A, with t= 0.009) B. In patAfter PSM, the OS and RFS rates of patients with tumours smaller than 5 cm in the AR group were significantly better than those in the NAR group. For tumours equal to or larger than 5 cm, there was no significant difference in the OS and RFS between the AR and NAR groups.Cox regression analysis demonstrated that AR affected OS outcomes in tumours smaller than 5 cm  but did Cox regression analysis also demonstrated that AR was associated with improved RFS in tumours less than 5 cm in size  but not This retrospective study included consecutive patients who underwent curative hepatectomy for HCC divided into PS-matched cohorts based on the extent of resection. Our data demonstrated that the extent of hepatic resection (AR or NAR) had different impacts on the survival outcome and recurrence rate of HCC when HCC was analysed according to tumour size. For tumours smaller than 5 cm, AR demonstrated superior survival outcomes (both OS and RFS) compared to NAR. Conversely, for tumours equal to or larger than 5 cm, the survival outcomes of AR and NAR were comparable.AR is based on the high propensity of HCC to invade intrahepatic vasculature by spreading through the closest portal veins . SystemaAR is known to be associated with longer operating times and more intraoperative bleeding compared to NAR. Through technical innovations in surgery, improvements in perioperative care, and enhanced understanding of liver anatomy, morbidity and mortality after hepatic resection are now acceptable and conquerable. Despite these advances, post-hepatectomy liver failure (PHLF) still remains an unresolved and devastating morbidity after major hepatectomy . More fuThe criteria for patient selection and the extent of hepatectomy tend to differ among surgeons and centres. As such, multicentre studies and studies that analyse cases performed by several surgeons at a single centre may be more prone to bias. The current study was unique because it examined consecutive cases of hepatectomy for HCC performed by a single surgeon at a single centre. To the best of our knowledge, this is the first study to analyse the outcomes of AR and NAR for HCC performed by a single surgeon. While a single-centre, single-surgeon study may be prone to selection bias, it provides consistent data, particularly in terms of the surgical technique and decision process for the extent of resection (AR vs. NAR). Further, we analysed a large number of hepatectomies performed by a single surgeon, which enhanced the quality of our study results.The best opportunity for cure in patients with HCC is during the first instance of surgical intervention, so determining the extent and timing of resection is crucial for improving patient survival. The primary concern in HCC is recurrence following treatment. In this study, multiple HCC tumours larger than 5 cm affected overall survival outcomes, whereas for tumours smaller than 5 cm, AST and albumin levels, histologic characteristics, and the extent of resection did affect the survival outcome. Further, recurrence was more likely among male patients and those with poor liver function and multiple tumours, regardless of tumour size. AR seemed to reduce the risk of recurrence and improved survival in patients with tumours smaller than 5 cm. Our data also suggested that in tumours greater than 5 cm, the tumour biology itself may be more important than the extent of resection. Because the prognostic factors in pathology could be acquired only after the surgery , predicting these risk factors preoperatively through an imaging study is crucially important in deciding the best treatment choice for the patient. A recent well-designed clinical study proved a strong association between Liver Imaging Reporting and Data System (LI-RADS) classification and pathological findings, which proved to be significant prognostic factors  for patient survival outcomes . FurtherThe limitations of this study include its retrospective single-centre design and a discrepancy in the sample size between the AR and NAR groups. A selection bias, therefore, remained between the two groups even though PSM was conducted to adjust for baseline clinical characteristics and liver functions. Further randomised controlled trials are required to confirm the role of AR and NAR in HCC patients according to tumour size.This retrospective PS-matched study compared the benefits of AR and NAR performed by a single surgeon for curative resection of HCC. In HCCs smaller than 5 cm, AR demonstrated a favourable survival benefit over NAR. However, for HCCs larger than 5 cm, AR and NAR demonstrated comparable survival outcomes. Further well-designed comparative studies are needed to identify which patients benefit from AR in HCC when factors other than tumour size are considered.


Testosterone signaling mediates various diseases, such as androgenetic alopecia and prostate cancer. Testosterone signaling is mediated by the androgen receptor (AR). In this study, we fortuitously found that primary and immortalized dermal papilla cells suppressed AR expression, although dermal papilla cells express AR in vivo. To analyze the AR signaling pathway, we exogenously introduced the AR gene via a retrovirus into immortalized dermal papilla cells and comprehensively compared their expression profiles with and without AR expression.Whole-transcriptome profiling revealed that the focal adhesion pathway was mainly affected by the activation of AR signaling. In particular, we found that caveolin-1 gene expression was downregulated in AR-expressing cells, suggesting that caveolin-1 is controlled by AR.Our whole transcriptome data is critical resources for discovery of new therapeutic targets for testosterone-related diseases.The online version contains supplementary material available at 10.1186/s12863-021-01018-6. The comprehensive gene expression profiling were obtained by RNA-Seq analysis about AR negative and AR positive dermal papilla cells.The bioinformatics analysis suggested that caveolin-1 and EGF receptors are the downstream of AR signaling.Our study showed the combination of pinpoint mutant cells and global transcriptome is effective to identify the downstream genes.The online version contains supplementary material available at 10.1186/s12863-021-01018-6. The software and its versions were used for the data analysis.https://www.bioinformatics.babraham.ac.uk/projects/fastqc/FastQC, version 0.11.8 was used for quality check of raw FASTQ sequencing file. http://prinseq.sourceforge.net/PRINSEQ, version 0.20.4 was used for the removal of low quality reads. https://github.com/jhhung/PEATPEAT, version 1.2 was used for the removal of the adaptor sequence. https://github.com/alexdobin/STARSTAR, version 2.6.1 was used for the mapping. http://subread.sourceforge.netfeatureCount, SUBREAD, release 1.6.5 was used for the expression counting. https://www.r-project.orgR package, version 4.0.3, was used for the downstream analysis. https://github.com/swsoyee/TCC-GUITCC-GUI, tool for the downstream analysis. Testosterone is a hormone that controls cell growth or sexual differentiation of the reproductive organs. This hormone is known to be associated with various diseases, such as androgenetic alopecia (AGA) and prostate cancer. Approximately 30% of males are reported to be affected by AGA . The mecThe hair growth is controlled by the growth signal from human follicle dermal papilla cells (HFDPCs). Interestingly, Kwack et al. showed that primary HFDPCs cause a decrease in AR expression even after passage 6. In agreement with this phenomenon, we could not measure the expression level of AR, even in early passages of primary HFDPCs . AlthougK4, cyclin D1, TERT). We previously confirmed that AR expression in established immortalized cells (HFDPC_K4DT) is undetectable, almost identical to that of fibroblasts. To reconstitute the AR signaling pathway, we introduced an expression cassette of AR with an HA tag through the retrovirus expression system. Total RNA was extracted from immortalized HFDPCs using the K4DT method and AR-expressing immortalized HFDPCs. To detect the reproducibility of the expression counts, we extracted RNA from three biological replicates.We previously reported the establishment of immortalized DPCs with the expression of R24C mutant cyclin-dependent kinase 4 (CDK4), cyclin D1, and telomerase reverse transcriptase (TERT) via lentiviral gene transfer. The immortalized human follicle dermal papilla cells were named as “HFDPC_K4DT” from the last characters of the introduced genes (CDhttps://infinityloop.shinyapps.io/TCC-GUI/). For the determination of differentially expressed genes, we used Q value (FDR) less than 0.01.We checked the quality of the raw sequencing reads using FastQC. Data were obtained using paired-end sequencing. We analyzed the data from six samples of HFDPC-K4DT and AR-expressing HFDPC-K4DT. Raw sequencing reads were processed with PEAT program to remove the adaptor sequence. We removed the low-quality reads using PRINSEQ, and the remaining reads were mapped to the human reference genome GRC38, NCBI) with the STAR mapping program. The expression counts for each sample were obtained using the featureCounts program. We first extracted genes which have more than 3000 counts on any sample. To normalize expression counts, we used the DEGES normalization method . We set , NCBI wiAfter mapping all sequencing reads, the expression count of all genes was determined . Based on the results of DEGs in TCC-GUI, we extracted 1196 genes classified as DEGs. The list of DEGs was processed using the DAVID pathway analysis tool. The expression levels of genes in the listed pathways were visualized using the heatmap function of TCC-GUI.The total RNAs of HFDPC-K4DT and AR expressing K4DT cells were extracted with NucleoSpin RNA . The cells were treated with basal medium containing 50 nM DHT or without DHT (no treatement) for 8 h. Total cDNAs were obatained with PrimeScript RT reagent Kit with gDNA Eraser with random primer method. The cDNA were used as the template samples of qRT-PCR with THUNDERBIRD SYBR qPCR Mix  under the reaction condition recommended from the manufacture. The sequences of the detection primers were listed in below. Primers for caveolin 1, TF1162; 5′-CCCGCAGCCTGGGAGTGCCCTGA-3′ and TF1163, 5′-GCTTGTAGATGTTGCCCTGTTCCCGGAT-3′. Primers for EGFP, TF1164, 5′-ATGATGCAAATAAAACCGGACTGAAGGA-3′, TF1165, 5′-CTGCACCCCAGCAGCTCCCATTG-3′. Primers for GAPDH, TF999, 5′- GAGGTGCACCACCAACTGCTTAGC-3′ and TF1000, 5′-TCGGCATGGACTGTGGTCATGAG-3′. The detections with qRT-PCR were carried out with Thermal Cycler Dice Real Time System II  under the relative quantitation with GAPDH.In our previous study, we exogenously introduced an AR expression cassette through retrovirus gene transfer. Although the expression level of AR was undetectable in parent cells, the AR-expressing immortalized HFDPCs showed an intense signal with the expected molecular weight in western blotting  and a 150-bp paired end. The sequencing workflow is shown in Fig. https://figshare.com/articles/dataset/HFDPC_K4DT_HFDPC_K4DT_AR/13567343). The sequencing data were submitted to the DDBJ database under Bioproject Submission ID PRJDB10909. We first filtered genes at least 3000 counts on any sample. The number of genes remained after the filtration was 1537 genes. Next, we input the expression counts of the whole genome into TCC-GUI. First, we analyzed the correlation plots of expression profiles, as shown in Fig. The complete list of expression counts of parent HFDPC-K4DT and AR-expressing HFDPC-K4DT is provided in Figshare , followed by Proteoglycans in cancer (51 hits in the annotation list). Based on the pathway analysis results, we compared 61 genes listed in focal adhesion using heatmap analysis Fig. . FurtherIn Proteoglycans in cancer related pathway, the expression level of Twist was elevated which is one of the transcriptional factor in AR expressing cell.We furthermore detected the expression levels of Caveolin 1 downregulated and EGFR with qPCR analysis. As the first evidence, we detected expression of these two genes in identical RNAs which used for RNA-Seq. The downregulation of Caveolin 1 and upregulation of EGFR in AR expressing cell were reproduced with qPCR analysis Fig. . FurtherIn this study, we comprehensively compared the expression profiles of parent immortalized human HFDPCs with K4DT and AR-expressing offspring cells. The genetic background of these cell lines was identical except for the expression status of AR. The comparison of global expression profiles allowed us to identify the downstream genes involved in AR signaling.We already detected that HA-labelled androgen receptor get into the nuclei without treatment of testosterone in AR expressing cell in our previous publication. The nuclear localization of exogenously introduced HA-labelled androgen receptor without ligand treatment can be possibly explained by following two reasons; first possibility is the auto-dimerization. Due to the high level of expression of HA-labelled AR, receptor might cause auto-dimerization, which is critical process for the activation of AR signaling. The second possibility is the testosterone concentration within the serum in cell culture medium. Since the testosterone is quite sensitive as the hormone receptor, we need to perform serum withdrawn to exactly detect the nuclear translocation. We furthermore carried out the exposure of 50 nM DHT to parent K4DT cell and AR expressing cell. The exposure of DHT causes the elevation of Caveolin 1 even in the AR negative parent cell. The results of DHT exposure in parent cell showed that DHT treatment causes changes in signaling pathway, which independent from AR manner. We need to pay attention for the use of the ligand. If we use synthetic antrogen recptor ligand, such as R1881, the effect of ligand treatment might show different response. However, although the synthetic ligand might be specific from the view point of androgen signaling pathway, the biological explanation would be difficult when it compared with natural ligands such as DHT.We found that caveolin-1 is downregulated in AR-expressing cells. In support of this result, caveolin-1 is reported to be controlled by AR signaling . FurtherOur whole transcriptome data is critical resources for discovery of new therapeutic targets for testosterone-related diseases.Additional file 1.Additional file 2.Additional file 3.Additional file 4.Additional file 5.Additional file 6.Additional file 7.Additional file 8.Additional file 9.Additional file 10.Additional file 11.


Intermediate transpedicular fixation, i.e. additional insertion of transpedicular screws into the injured vertebrae, is an improvement to the most popular surgical intervention for spinal injuries, currently gaining widespread use in clinical practice. Unilateral insertion of transpedicular screws into the injured vertebrae allows combining the advantages of intermediate transpedicular fixation with the possibility to perform anterior column support without remounting the transpedicular system.The aim of the study was to use biomechanical computer modeling for evaluating the stability of intermediate transpedicular fixation components, which allow performing anterior column support if necessary.DICOM files obtained during CT scan of a patient with intermediate thoracolumbar spine injury and the ANSYS software were used. Stability of the transpedicular system and supportability of the complementary Mesh implant installed with unilateral intermediate transpedicular screws were evaluated using computer modeling based on the finite element method.The values of stress and displacement fields for spine–hardware systems with various arrangements have been obtained. The maximum loads exceeding bone tissue strength (153–161 MPa) were registered for standard 4-screw system (190 MPa) when modeling the load equivalent for walking and falling from a standing position. The use of the proposed fixation system arrangement supplemented with intermediate screws allows obtaining loads in the spine–hardware system not exceeding these thresholds. Complementary eccentric Mesh implant enhances fixation stability of the transpedicular system with intermediate screws.The results show the high degree of mechanical stability of the proposed hardware arrangement and its potential efficacy for thoracolumbar transitional vertebra stabilization. Of thesinjuries . The proinjuries –8. Howevinjuries . Therefoinjuries .The stability of bone-hardware system with short-segment and multi-segment fixation is improved as a result of bilateral insertion of transpedicular screws into the injured vertebra — the intervention is called intermediate screw fixation , 15. WitThe details of application of intermediate transpedicular screws and implementation of ventral spinal fusion using transpedicular systems of such arrangement are insufficiently illuminated in the available literature. This was the basis for our experimental research.The aim of the study was to use biomechanical computer modeling for evaluating the stability of intermediate transpedicular fixation components, which allow performing anterior column support if necessary.It is possible to predict the “survival” of the spine–hardware system using biomechanical computer modeling. Its mathematical basis is the finite element method, a numerical method for solving partial differential equations as well as integral equations that arise when solving problems of applied physics. The method is used to solve the problems of mechanics of deformable solids, an example of which is an instrumented spine. Currently, this technology can be used as an element of preoperative planning –23.12 and L1. She underwent X-ray of the spine in two projections in a standing position in all body mode and computed tomography (CT). DICOM files obtained by CT and X-ray examination served as initial data for constructing a solid-body model of the instrumented spine. At the first stage, a three-dimensional computer model of the spine was created, followed by making three-dimensional models of transpedicular fixation systems. Next, the models of fixation systems and the spine were combined taking into account the spatial arrangement of the spine according to X-ray data in a standing position.The use of this technology will be shown by the example of treatment of patient I., 60 years old, with vertebral compression burst fractures of ThTo plan the possible options for configuring the hardware, biomechanical modeling was performed based on DICOM files obtained during introscopic studies. Virtual testing of each model made it possible to study stress-strain behavior in the spine — hardware system. Using the ANSYS finite element analysis software, it was possible to calculate and analyze stresses arising in the vertebrae, intervertebral discs, and the transpedicular system when applying the guiding load and loads arising from flexion, extension, bending to the right and left, and during multidirectional rotation. Load characteristics  corresponded to the averaged anthropometric data of the patients. The mechanical characteristics of the spinal column and implants were borrowed from the available literature –26.When planning spondylosynthesis during biomechanical computer modeling, we considered the following design options for fixation systems shown in 11–L2 (transpedicular system with 4 screws inserted into the vertebrae adjacent to the injured ones);A — fixation in segments Th11–L2 (the system is supplemented by intermediate transpedicular screws inserted into the vertebrae Th12 and L1 on the left);B — fixation in segments Th11–L2 (transpedicular system with 4 screws inserted into the vertebrae adjacent to the injured ones), groove type resection of injured vertebral bodies, installation of Mesh support cage along the central axis of the vertebral bodies;C — fixation in segments Th11–L2 (the system is supplemented by intermediate transpedicular screws inserted into the Th12 and L1 vertebrae on the left), groove type resection of the injured vertebral bodies, installation of Mesh support cage with a shift to the right of the central axis of the vertebral bodies.D — fixation in segments ThPatients aged over 40 years have an increased risk of transpedicular system instability associated with post-traumatic osteonecrosis of the injured vertebra . Therefo11 vertebral lamina. When modeling bending , a 7.5 N·m force was applied. Movements were restricted in the lower contact plate L2.To simulate the axial stress, a 400 N force was applied to the ThAll materials were considered perfectly elastic, isotropic. The properties of the materials are presented in According to the modeling data, stress and displacement fields shown in The calculation results for all loading options and fixation systems are summarized in In terms of biomechanics, both the 4-screw and 6-screw structures provide the necessary stability for the patient in a standing position with a load corresponding to their weight. Mesh cage structures are more stable, provide more rigid fixation, therefore higher stresses appear in bone structures with Mesh installed. By contrast, higher equivalent stresses occur in the transpedicular structure when Mesh is absent.The screws receive the major load. The Mesh cage takes over part of the load, if installed, so the screws are less loaded. This situation occurs when loads corresponding to a standing position and bending in different directions without additional load are simulated.·m) are given in If we evaluate and compare the options for surgical interventions when modeling a compression load corresponding to walking or falling from human height, the picture of stress distribution will be significantly different. For example, in order to simulate a fall from human height, the compression load applied to the models was increased to 1200 N. The calculation results for this compression load in combination with the moment simulating the body bending forward .12 and L1 vertebrae ” ” . The injthe left . The posControl CT examination performed 6 months after the intervention revealed lack of supportability and signs of aseptic osteonecrosis of the damaged vertebral bodies .11–Th12, Th12–L1, L1–L2 and partial groove-type resection of the Th12 and L1 vertebral bodies were performed via the right thoracophrenotomy approach. The Mesh container implant was placed in the formed bone bed, filled with autologous bone mixed with synthetic bone substitute  into the damaged vertebrae . IntermeWhen planning the surgical intervention described above, we attempted to combine the advantages of intermediate screw fixation technique with the possibility of installing a Mesh container implant in the future. For this, additional screws were inserted into the damaged vertebrae on the left . When planning the surgery, we looked at the unilateral left insertion of transpedicular screws into the damaged vertebral bodies as the so-called safety technology, which allows increasing the transpedicular system stability while preserving the possibility to fit prostheses for the damaged vertebral bodies if necessary.At present, the anterior column support is usually performed with a mesh implant (Mesh), filled with autologous or allo-bone. In most cases, endoprosthesis is installed in the center of the resected vertebral body, though in the literature there are also variants with different locations and even different number of installed container implants , 34. Thi12 and L1 vertebrae using biomechanical computer modeling allows obtaining significantly more rigid fixation than a 4-screw system. Certainly, in this option of using intermediate transpedicular screws, subsequent Mesh implantation is possible only with a displacement relative to the central axis of the vertebral bodies. Analysis of stress distribution in the bone–implant system and the vertebrae adjacent to the fixation area is actually no different from the variant with Mesh installed in the central position.Introduction of intermediate screws into the damaged ThTranspedicular fixation with unilateral insertion of intermediate screws into the injured vertebrae can be considered a promising technology in surgical treatment of patients with thoracolumbar burst fractures. According to biomechanical modeling data, the stability of transpedicular system supplemented by intermediate screws is higher than that of standard structures.In case of installing a cage (with both 4- and 6-screw intermediate transpedicular fixation), the maximum equivalent stresses are close to the limit value. With the 4-screw version, they actually reach the lower range limit, which indicates that this option is less favorable than the 6-screw version. Central or eccentric location of the Mesh implant does not affect spine–hardware system stability.Thus, when using the transpedicular system both alone and in combination with anterior column support, the decision to apply intermediate fixation is more rational  in terms of biomechanics. This technology is appropriate when there is a risk of developing post-traumatic osteonecrosis of compressed vertebrae or it is impossible to recline them. Unilateral application of intermediate transpedicular screws makes it possible to perform subsequent anterior column support easily without re-mounting the entire system. Moreover, off-center installation of Mesh implants in relation to the central axis of the vertebral bodies is not followed by a decrease in spine–hardware system stability.


In order to make most patients recover most of their limb functions after rehabilitation training, virtual reality technology is an emerging human-computer interaction technology, which uses the computer and the corresponding application software to build the virtual reality environment. Completing the training tasks in the virtual environment attracts the patients to conduct repeated training in the game and task-based training mode and gradually realizes the rehabilitation training goals. For the rehabilitation population with certain exercise ability, the kinematics of human upper limbs is mainly analyzed, and the virtual reality system based on HTC VIVE is developed. The feasibility and work efficiency of the upper limb rehabilitation training system were verified by experiments. Adult volunteers who are healthy and need rehabilitation training to participate in the experiment were recruited, and experimental data were recorded. The virtual reality upper limb rehabilitation system was a questionnaire. By extracting the motion data, the system application effect is analyzed and evaluated by the simulation diagram. Follow-up results of rehabilitation training showed that the average score of healthy subjects was more than 4 points and 3.8 points per question. Therefore, it is feasible to perform upper limb rehabilitation training using the HTC VIVE virtual reality rehabilitation system. Hemiplegia patients participating in practical rehabilitation training can gradually recover most of the functions of the affected limb. Effective rehabilitation training requires patients to participate in repeated rehabilitation training purposefully and actively for a long time. Stroke rehabilitation takes a long time and requires high training intensity, which requires a long period in the recovery process after stroke . HoweverVirtual reality technology creates a virtual environment through highly configured computers, related equipment, and specialized application software and lets people immerse themselves in the virtual environment. Virtual reality technology allows users to achieve a high level of presence . By applThe repetition of a single action in rehabilitation training determines the dullness and unclear goal of rehabilitation training. Through the high-speed computing power of the computer, virtual reality technology transmits computer-generated images to the observer to create an immersive feeling , 5. ThenA task-oriented VR rehabilitation training system is designed and developed for the VR device HTC VIVE. When patients wear the device for rehabilitation exercise, it can interact with the virtual environment to improve the efficiency and interest of rehabilitation training.Virtual reality (VR) technology is a potential tool for cognitive process assessment and rehabilitation. The application research of virtual reality technology in rehabilitation training is developing continuously. Hwang et al. explored the effects of robot-assisted (RA) virtual reality (VR) intervention on motor function (MF) and neurological function (NF) in patients with stroke (CS) . MontoyaHTC VIVE, virtual reality equipment, designed and developed a virtual reality rehabilitation training system. Human upper limb movement is analyzed, a virtual reality system based on HTC VIVE is designed and developed, and finally, experimental verification is performed. Through repeated rehabilitation training, the purpose of upper limb rehabilitation training is achieved.HTC VIVE equipment wore end-to-end displays (HMD), a hand-held controller, and a positioner. Rehabilitation training users wore a display and a hand-held controller to interact with virtual objects in the real world. The locator captured the hand-held controller's location and rotary information and passed the data to the computer. After rehabilitation training system software for processing, the image was displayed on the head-mounted display and returned to the user .In the subject, according to the activity rules of human upper limbs and the characteristics of the HTC VIVE interaction mode, three representative movements of hand moving to the specified position points on the desktop, hand touching the position point above the shoulder, and holding a cup to drink water were extracted. These movements were very close to the movements in life. In the design of the scene, the virtual room was selected as the scene to enable the patients participating in rehabilitation training to carry out rehabilitation training in a “comfortable” virtual environment, thus easing the mood of the participants and improving their enthusiasm for rehabilitation training.While participating in the training, the rehabilitation training patients controlled their hands in the virtual world to conduct human-computer interaction. There are two main ways of human-computer interaction: touch and grab. As shown in the figure, when the manipulator grasps the water cup to complete the drinking action, it triggers the two actions of touching and grasping. First, touch the water cup to the front of the body from the starting position of the action, and then use the trigger button of the hand-held controller to control the hand to grasp the water cup in the virtual world. Then, send the water cup to the mouth to complete the drinking action , 17. DurIn the virtual world, objects need to be represented by various shapes of models, such as mountains, water, people, and animals. These objects need to be represented by modeling. The common modeling method is through modeling software. The simple schematic model can use the basic shape of the virtual reality engine for modeling. The success of a virtual reality scene depends on whether the user experiencing the virtual reality scene is immersed in the scene and whether the scene brings a strong sense of immersion to the user. It focuses on the light and shadow effect of the scene, the simulation effect of the model, and the physical constraints of the objects in the scene. The rehabilitation training environment set by this project is the living room in the family, so modeling technology is required to be used for modeling . Unreal Debug the HTC VIVE rehabilitation training system to a normal working state, including system start-up, HTC VIVE operation room setting, rehabilitation training application software system start-up, and debugging.The subject is seated on the chair, and the experimental table is located in front of the subject.Adjust the height and position of the chair according to the experimenter's height and dominant hand (the default use of the right hand). First of all, make sure that the subjects' upper limbs move within a comfortable range during the experiment. Secondly, in the adjustment process, the height of the shoulder joint can be adjusted to make the subjects' sitting posture and movement more comfortable, with making the movement posture more standardized.The volunteers in the experiment hold the controller and place it at point A 25 cm in front of the body.Complete training actions 1, 2, and 3 according to the subject's ability.This experiment extracted three rehabilitation training movements, which involved the shoulder joint's internal and external rotation and the elbow joint's flexion and extension. The training program of movement 1 is the movement of the wrist from starting point A to points B, C, and D, as shown in As shown in The training program of action 2 is the movement of the wrist from starting point A to the ipsilateral shoulder and then from the ipsilateral shoulder to the target point of the opposite shoulder, as shown in As shown in The training program of action 3 is to grasp the water cup in the virtual world with the wrist from starting point A to D and then deliver the water cup to the mouth, as shown in As shown in This topic introduces a rehabilitation training system in a virtual environment. Due to the accurate tracking of HTC VIVE, the experimental results show that it is feasible to introduce HTC VIVE into upper limb rehabilitation, which increases the interest in rehabilitation training, and is suitable for family rehabilitation with low difficulty and cost.Future work will focus on people with different exercise levels and design exercise programs with different exercise intensities. So far, each movement has only one intensity. By setting different intensity training, it is expected to meet the needs of different groups of people. In addition, a more convenient interaction model should be designed with the rehabilitation robot of the upper limb exoskeleton to facilitate rehabilitation training for patients of different degrees.In the experiment, each set of movements should be repeated many times, and the frequency and amplitude of the movement can be adjusted autonomously. And keep the torso and head as still as possible while the arms are moving. Each session lasted about four minutes, and after completing two tests, participants filled out a Likert scale. The posttest questionnaire has a maximum score of 5 (1 is the lowest and five is the highest). The questionnaire aims to collect information on the accuracy, fun, and ease of using the HTC VIVE VR rehabilitation system. Six subsequent patients were enrolled in the test. The purpose of the test was to initially check the effectiveness of the HTC VIVE and VR systems. Similarly, patients wearing an HTC VIVE head-mounted display led to three sets of actions. After completing the test, the patients filled out a questionnaire.In the questionnaire results, as shown in The experiment of the virtual reality upper limb rehabilitation training system proves the feasibility of this system in rehabilitation training. The upper limb rehabilitation training program based on HTC VIVE virtual reality was formulated. The movement coordination, motion accuracy, movement completion, and HTC VIVE equipment usability index were qualitatively analyzed when the system was used for rehabilitation training. Finally, a questionnaire survey was carried out for the system. The analysis results further confirmed the system's feasibility, and some problems that should be paid attention to in clinical use were also found. To sum up, the virtual reality upper limb rehabilitation training system studied in this study is feasible, can increase the interest in upper limb rehabilitation training, and provide feedback and evaluation for rehabilitation training.


Frontal fibrosing alopecia is a scarring alopecia, the prevalence of which is increasing worldwide since its first description in 1994. The reason for this emerging epidemic may be a higher exposure to an unknown trigger, although its aethiology and pathogenesis still remain enigmatic. Clinical, trichoscopic, sonographic, and histopathologic findings are allowing clinicians to understand more aspects about this type of cicatricial alopecia. Several treatments have been used in frontal fibrosing alopecia, although the 5-alpha reductase inhibitors seem to be the most promising. The aim of this report is to provide a compilation about the published data regarding frontal fibrosing alopecia in a narrative review. Frontal fibrosing alopecia (FFA) was described in 1994 by Kossard as a progressive scarring alopecia in postmenopausal women, affecting the frontal and temporoparietal hairline, and was initially called postmenopausal frontal fibrosing alopecia . HoweverThe aim of this report is to perform an updated and complete review about FFA regarding epidemiology, aetiopathogenesis, clinical characteristics , prognostic factors, histopathology, diagnosis, differential diagnosis, and treatment. For that, an exhaustive review of all of the references related to FFA and published in PubMed has been done by searching for “frontal fibrosing alopecia”, including references written in English, Spanish, German, and French, from 1994 to 2021. A total of 487 articles have been reviewed. Articles with a more significant number of patients have been included. In addition, publications with a lower number of patients that provided new information about FFA have also been incorporated.There are no specific data about the worldwide prevalence of FFA so far. Recently, the overall crude prevalence for FFA in New York City has been estimated at about 0.015% .FFA was described initially as affecting almost exclusively postmenopausal women. However, although this group seems to be the most frequently affected, it is not the only one. The first report of a man with FFA dates from 2002 , but manThe mean age of onset of FFA ranges from 56 to 63 years ,17. EvenMale patients with FFA seem to be affected with FFA at a younger age than women, with a mean age of onset of 47.3 years . FFA in Regarding the human race, FFA has been described worldwide, although most cases have been reported in European and North American countries, mainly among Caucasians and fewer among black-skinned populations , whereasWith reference to external factors, a study found that patients with FFA belonged to a more affluent group compared to both a comparable control group with other types of alopecia and to a general control group .The aetiopathogenesis of FFA remains unknown, although hormonal factors, autoimmunity, genetic susceptibility, and some exogen factors are thought to play a role  14]..14].The loss of the immune privilege of the hair follicle would be the starting point in the development of scarring alopecias . This buThe onset and progression of FFA in a woman with psoriasis, treated with ustekinumab , suggests that the Th1 and Th17 pathways do not play a major role in FFA . On the one hand, in LPP, the downregulation and the abnormal function of the peroxisome proliferator-activated receptor γ (PPAR-γ) have been proposed as the initial triggers of the inflammation. PPAR-γ plays a central role in lipid homeostasis and in the differentiation and maturation of sebocytes . TargeteThe mammalian target of rapamycin (mTOR) is a pathway that combines signals and acts as a central regulator for metabolism, growth and cell proliferation, and is a major regulator of adiposity due to PPAR-γ activation . A recenMoreover, transmission electron microscopy and global metabolomics profiling data have identified defects in mitochondrial β oxidation of fatty acids, leading to the accumulation of medium- and long-chain fatty acids, along with decreased levels of (antioxidant) glutathione and elevated levels of oxidized glutathione (a marker of oxidative stress) in both lesional and non-lesional FFA scalp samples. Therefore, mitochondrial dysfunction may be an early process in the pathogenesis of FFA .The expression of Snail1 noted in the fibrotic dermis in FFA suggests that the fibroblasts are, in part, derived from the hair follicle via an epithelial-mesenchymal transition process . The traOn the other hand, the expression of Janus kinase (JAK) 1 and 3 are significantly upregulated in dermal inflammatory cells in patients with LPP . TherefoNeurogenic inflammation is another hypothesis for the pathogenesis of scarring alopecias . The totA new hypothesis proposes that FFA may arise as a result of excessive facial photo-protection, with a resultant disturbance in immunological homeostasis mediated via the aryl hydrocarbon receptor-kynurenine pathway axis (AhR/KP), leading to the collapse of immune privilege at the hair bulge . OverexpA new study has identified the presence of circulating microRNAs as being highly predictive of disease status in FFA .Hormonal factors are thought to play a role in FFA, due to their higher frequency in women, especially postmenopausal ones, and their response to 5-alpha reductase inhibitors . T. T22]. TYellow dots may also be found in FFA, and may be an early feature associated with follicles with a potential for regrowth ; therefoIn the temporal area, where follicular hyperkeratosis and perifollicular erythema are rarely seen ,151, a cThe presence of solitary terminal hairs at the site of the original hairline  and the Although perifollicular erythema has been considered as a marker of FFA activity  and manyIn the eyebrow area, the presence of a few black dots and dystrophic hairs may suggest the diagnosis of FFA . Red or Four dermoscopic patterns of LPPigm in patients with FFA have been described: pseudo-network, speckled blue-grey dots, dotted pattern, and blue-grey dots arranged in circles . A recent study found that telangiectasias, red dots, follicular plugs, and perifollicular erythema are more frequent in phototypes I–III, while peripilar hyperpigmentation, black dots, dystrophic hairs, short thin hair/vellus, peripilar casts, and broken hairs are more frequent in phototypes IV–VI . Vascular structures (arborizing vessels and extravasated hemorrhages) become more common when there is chronic use of topical corticosteroids, whereas perifollicular erythema and the peripilar cast become less visible .Ultraviolet light-enhanced trichoscopy may be helpful to predict the efficacy of local treatment, so that positive fluorescence (“starry night sky sign” pattern), which is due to the presence of Propionibacterium acnes, may be a sign of a still-preserved hair follicle .A five-grade classification to assess the clinical severity of FFA has been proposed: I (<1 cm), II (1–2.99 cm), III 3–4.99 cm), IV (5–6.99 cm), and V . This size is obtained by measuring the area of cicatricial skin produced by the recession of the frontal and temporal hairline and using the largest measurement to define the grade of severity [–4.99 cm,Currently, two validated scoring systems for FFA assessment exist: the FFASI (FFA Severity Index), which gives scores for hairline recession, inflammatory band, non-scalp loss, and associated features , and theBlood analysis, including hemogram, general biochemical, liver function, thyroid function, antinuclear antibodies, and sex hormones, is usually normal . Low levOptical coherence tomography in FFA has shown increased epidermal thickness in the inflammatory hairline and decreased thickness in the alopecic band, as well as a lower vascular flow in the alopecic band compared to the inflammatory scalp in the superficial dermis, but increased flow in the deeper plexus . Reflectance confocal microscopy in LPP and FFA allows visualization of the major key diagnostic features, such as infundibular hyperkeratosis, perifollicular lichenoid inflammatory infiltrate, and extensive perifollicular fibrosis .Regarding sonography, FFA patients have a higher vessel diameter and flow in the hairline implantation area in comparison with a control group, which may be explained by the presence of active inflammation . InteresHistological findings in FFA seem to be indistinguishable from LPP, according to some authors . FFA is The loss of sebaceous glands is an early finding in FFA . Indeed,Vacuolar degeneration of the basal layer, keratinocyte necrosis, and replacement of the pilosebaceous units by fibrous tracts, along with loss of elastin fibers, are other FFA signs . AdvanceInitially, it was considered that intermediate and vellus-like follicles were more commonly affected than terminal follicles by the lymphocytic inflammatory infiltrate and perifollicular fibrosis . NowadayRegarding the composition of the inflammatory infiltrate in FFA, this is characterized by an increase in the percentage of CD8+ T cells ,172, witA lower melanocyte count has been demonstrated in the upper follicle in FFA patients compared to LPP, and is associated with the hypopigmentation observed clinically in the alopecic band in FFA ,30. A recent study provides data for significant immune dysregulation in FFA, with increased infiltration of CD8+ T cells, CD11c+ dendritic cells, CD69+ and CD103+ TRM, tryptase+ mast cells, and FOXP3+ Tregs, in addition to significant upregulation of Th1 and JAK-STAT pathways . MoreoveFew histological abnormalities have been described in clinically unaffected scalp in FFA and LPP, such as infundibular lymphocytic inflammation ,175,176 Recently, dermal fat infiltration at the isthmus level and in the arrector pili muscle has been observed in FFA samples . InteresBiopsy of the facial papules also reveals follicular hyperkeratosis and lichenoid dermatitis involving the infundibular and isthmus portions of the vellus hair follicles , or evenWith regards to eyelashes, small and narrow bulbs, irregular caliber, and irregular pigment distribution have been observed. Demodex folliculorum infestation was noted in a patient with mild FFA and eyelash loss, which suggests that it might accelerate autoimmune inflammation and produce premature eyelash alopecia .Whether FFA is a variant of LPP or a different entity is still unclear ,3. CliniFFA and LPP share main histological features. However, a few differences have been found between LPP and FFA , which mA lower melanocyte count has been demonstrated in the upper follicle in FFA patients compared to LPP .Diagnostic criteria for FFA are referred to in The ophiasis pattern of AA, which affects the margins of the scalp, may masquerade as FFA. In addition, AA may produce eyebrow alopecia, sometimes as an isolated finding. However, perifollicular erythema and hyperkeratosis are absent in AA, whereas yellow dots, dystrophic and broken hairs, black dots, exclamation mark hairs, tapered hairs, and regrowing hairs are common features . Traction alopecia may resemble FFA. The clinical background, with a history of use of tight hairstyles and the absence of typical trichoscopic signs of FFA, may be useful. Moreover, traction alopecia is not associated with eyebrow hair loss.Other scarring alopecias, such as LPP, discoid lupus erythematosus, and pseudopelade of Brocq, tend to produce multifocal alopecic areas. A familial high frontal hairline should also be discarded.AGA with male pattern may also be considered, especially when the frontal or temporal hairline is receded. However, hair miniaturization (with an increased proportion of thin and vellus hair) and anisotrichia  are not Almost all information about treatment in FFA is based on retrospective cohort studies and cases reports ,13,188. Topical corticoids are recommended, especially in the early inflammatory stage, but relapse occurs upon their discontinuation ,188. PotWith regards to intralesional corticosteroids, 20 mg/mL of triamcinolone acetonide used in the hairline every 3–6 months) may obtain hair regrowth in some patients ; 34% of –6 monthsTopical minoxidil has not shown clinical improvement in the slowing down of the progression of the alopecia .Bimatoprost 0.03% eye drops, a prostaglandin analogue, may be used for eyebrow loss; a study involving three patients who applied it twice daily showed regrowth in two of them after nine months of treatment . It may Some authors referred to the fact that excimer laser may be effective in reducing inflammation and peripilar casts in patients with active disease . Applica2, five treatments with a one-month interval) injected into the frontotemporal hairline and eyebrows showed improvement in trichoscopic signs and no further hair loss after five months [One patient of recalcitrant FFA treated with platelet-rich plasma (PRP)  has been shown to produce a stoppage of hairline recession in almost 43% patients, but with a relapse when the treatment is stopped . IntramuA study including 36 patients revealed an improvement in symptoms and signs of FFA in 73% of patients treated with hydroxychloroquine, though most were partial responses. The maximal benefits were seen within the first six months of therapy. On the other hand, 60% of them produced a response to mycophenolate mofetil, though mainly partial ones . Other rA report including 102 patients treated with oral finasteride (2.5–5 mg/day), which inhibits the isoenzime type II of 5-alpha reductase, displayed that 47% of patients showed improvement (regrowth in the hairline) and 53% showed a stabilization of the alopecia . SubsequA retrospective analysis of 54 women with FFA treated with oral isotreinoin (20 mg/day), acitretin (20 mg/day), or finasteride (5 mg/day) showed a stoppage of progression in 76%, 73%, and 43% of patients, respectively . AlitretRecently, a study including 224 FFA patients has compared the effectiveness of oral dutasteride against other systemic treatments  and with a group receiving no systemic therapy  . AuthorsRegarding facial papules, an improvement of the facial skin surface and regrowth of vellus after six months of treatment with oral prednisone and antimalarials have been reported . A favorThe only randomized controlled trial is in regard to the use of oral isotretinoin  combined with topical clobetasol (0.05%) and tacrolimus (0.1%) compared to topical treatment alone in FFA . AuthorsOther treatments, such as griseofulvin, azathioprine, or tetracyclines, have shown no efficacy or inconsistent outcomes so far ,17,129. Pioglitazone hydrochloride (15 mg/day), an oral PPAR-γ agonist, showed improvement of itching and a decrease in the inflammatory infiltrate in a patient with LPP, but no remission ; howeverOral minoxidil has been demonstrated to improve the background hair thickness in LPP, especially in patients with diffuse LPP; however, the report excluded patients with FFA . FurtherWith regards to biological therapies, a study including 10 patients with recalcitrant LPP and FFA (2/10) who were treated with oral tofacitinib, a pan-JAK inhibitor, 10–15 mg/day from two to nineteen months, showed a clinical response in 80% of patients and clinical improvement in both FFA patients . One womA minimum of one to five years without activity is recommended before hair transplantation is used in scarring alopecias ,209. MosAccording the published data, a simplified algorithm of treatment is represented in FFA prevalence has increased during the last few years, and so has the interest of the medical community regarding its characterization, pathogenesis, and treatment. However, most studies are observational reports, so further investigations and clinical trials are needed to clarify important issues, such as the possible responsible trigger. In that way, further studies about hair and skin cosmetic routines in patients with FFA may be an interesting research prospect. Moreover, the study of the existence of environmental factors that may explain differences in the prevalence of FFA in different geographic areas could contribute to a better understanding of FFA. The precise knowledge of its ethology and pathogenic mechanisms may expose specific therapeutic targets. Although the use of 5-alpha reductase inhibitors has permitted the stabilization of a considerable number of patients, research for new treatments, such as oral minoxidil or biological therapies, is still lacking.


Attention is a basic and main mental task and can play an important role in the functioning of other brain abilities such as intelligence, memory, learning, and perception, and its deficit occurs in 80% of patients with traumatic brain injury. The use of game-based tools for rehabilitation is rapidly expanding. Cognitive rehabilitation via video games is an emerging hot topic in cognitive science. Serious games serve a specific purpose in addition to entertainment. They can be more engaging than exercises since they replace reward and motivation systems with real-world motivations as a complement for rehabilitation activities. This study was aimed at identifying and categorizing serious computer games used for attention rehabilitation and evaluating their effects. Six electronic databases  were searched in August 2021. The search strategy consisted of three main concepts of “serious game”, “cognitive deficits”, and “cognitive rehabilitation”. The inclusion criteria were (1) journal articles, (2) English language, (3) being published in the last 10 years, (4) human participants, and (5) game-based intervention. In the 30 included studies, 22 unique games were utilized for attention rehabilitation. Lumosity (20%), Brain Age (Dr. Kawashima's Brain Training) (10%), and MoHRS (6.66%) were the most common games among the studies. There were (57%) casual, (23%) action, (10%) simulation, and (10%) multiple genres. Of the 47 tools used in the studies, 5 utilized cross-modal oddball attention tasks, 4 utilized game performance, 3 utilized the paced auditory serial additional test (PASAT), and the rest employed other tools. A total of 73 outcome measures were related to attention, 42 measures did not have significant results, 30 were significantly improved, 1 was significantly deteriorated, and 4 articles did not have any specific measures for attention evaluation. Thus, the results revealed the positive effect of serious games on attention. However, issues such as absence of scientific teams, the variety of the disorders that cause defects, the variety of criteria, differences in measurements, lack of long-term follow-up, insufficient RCT studies, and small sample sizes should be considered when designing, developing, and using game-based systems to prevent bias. Attention is defined as a set of complex psychological functions that include focusing or engaging with the goal, enduring, and being alert for a long time. It is a feature in the human brain that allows a limited amount of information to be actively processed. This information is taken from the vast amount of information available to the senses, stored memory, and other cognitive processes . It is tThe attention control system is one of the most complex control procedures in our nervous system. Different networks distributed in the brain are involved in different aspects of the attention control system. Interactions between and within these networks of attention are mediated by various inhibitory and excitatory neurotransmitters. These neurotransmitters play a vital role in the proper functioning of the attention control system, and their interaction is essential. Any defect in neurotransmitter interactions can lead to dysfunction of attention networks and consequently dysfunction of the attention control system .Attention is defined as awareness of what is happening around us . Its defResearchers are now well aware that the brain is a more flexible organ than previously thought and is able to significantly repair damage by reorganizing itself, which is the basis of functional rehabilitation. This feature is called neuroplasticity of the brain . It is sStill, the most important challenge for therapists is how to encourage patients to perform rehabilitation programs frequently , 26. TodOver the past few decades, evidence has highlighted the positive impact of computer-based rehabilitation programs on a variety of deficiencies , 34–38. To investigate and identify the existing literature on the application of serious games for attention rehabilitationTo map and categorize the literature according to the study purpose, target group, measures methods, features and capabilities of games, analytical results, and interpretationTo evaluate the effects of serious games in cognitive rehabilitationIn this qualitative literature review, we summarize findings about serious games in attention rehabilitation. The objectives of this review are as follows:Herein, we present a systematic literature review of serious games for attention rehabilitation based on the PRISMA checklist 2020 . This reThe eligibility criteria were as follows: (1) being a journal article, (2) being written in English, (3) being published in the last 10 years, (4) human participants, and (5) providing any game-based intervention. Studies would be excluded from the study if they were (1) unrelated and (2) duplicated; (3) had unavailable full texts or were abstract-only studies; (4) were of other types, e.g., reviews, (5) involved no video games or cognitive rehabilitation; and (6) were protocols and studies only about Exergames.∗ OR video game∗ OR online game∗ OR applied game∗ OR serious game∗ OR gamification OR virtual game OR Mobile game∗ AND Cognitive Dysfunction OR Cognit∗ OR Attention defect∗ OR attention∗ OR perception OR concentration AND Remediat∗ OR Rehabilitat∗ OR Train∗ OR Therap∗ OR Readapt∗. The search strategies for each database are listed in supplementary According to the AMSTAR guidelines, at least two databases have to be searched in a systematic review . To obtaAfter importing the citations to EndNote 20, duplicates were detected and deleted by this software. To select studies, they were read in two phases, including their title or abstract and a full-text review by two independent reviewers. Disagreements in selection were resolved by a third reviewer. Studies were eligible for data extraction if they met all the inclusion criteria and did not meet the exclusion criteria in the opinion of the reviewers. Then, a Microsoft Excel 2016 data extraction spreadsheet was designed and used by all team members to collect data. The spreadsheet items included the following: title, journal, author, year, volume, pages, abstract, keywords, objective, disease, country, setting, target group, mean age of participants, name of the game, platform, description of the game, game genre, sample size, intervention group, control group, evaluation methods, outcome measures, results, and statistical methods. In the spreadsheet, some responses were in the open-answer format and some in the closed-answer format. The reviewers could choose the not clear option if they could not find the answer. To extract more information about games that were not fully described by the included article, Internet resources and other articles were searched. We also searched the websites of the games to obtain the latest release information.Because we aimed to provide a classification of articles and games available for attention rehabilitation and evaluate their overall effects, at this phase, we did not intend to conduct a meta-analysis on the data; therefore, we did not perform a quality assessment of the included studies.According to the objectives, comparative tables and figures are presented to describe and categorize the results. With a qualitative analysis method, we combined and analysed the results and no meta-analysis was performed due to the heterogeneity of the outcome measures and differences in the populations. Prior to this step, data were checked and refined to provide better results. Excel 2016 was used to present and analyse the data.The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram of the study selection process is displayed in Frontiers in Aging Neuroscience (n = 3) and PLOS One (n = 2), and 13 of 30 of these journals (43%) are ranked in quartile 1. All the other journals had published only one included article. Most of the studies were conducted in Europe 13 (43%), followed by 6 (20%) in North America, 5 (17%) in Asia, 3 (10%) in multiple countries, and other in Australia , Africa , and South America  . The journals with the highest numbers of publications were The mean age of the participants ranged from 5.2 to 79.4 years . The higAll included interventions belonged to different types of computer technologies involving gamification. On the other hand, there were various types of control groups. Most studies administered routine care to the control group (11 out of 30). However, one study compared a BCI video game (FarmerKeeper) with cartoons. Another study compared an active video game-based physical activity program with an aerobic exercise program. There was also a study comparing a popular brain training game (Brain Age) with a popular puzzle game (Tetris). One study also compared Lumosity and a simulation strategy game. In another study conducted using Lumosity for the intervention group, the control group participated in discussion sessions about general topics related to aging. A study compared Brainastic computerized cognitive training (CCT) with watching videos on history, art, literature, and science plus physical exercise as a control group. One study compared preselected games (Kinect Adventures and Kinect Sports) with a balance platform therapy (BPT) by the Biodex Medical Systems. Furthermore, one study compared the Medal of Honor: Rising Sun (MoHRS) with three control groups, including a placebo control arcade game (Tetris), a useful field of view (UFOV) training program, and routine care.Most studies had a sample size of more than 10 (25 out of 30). Studies with a small sample were often comprised a virtual reality (VR) or augmented reality (AR) intervention group . The largest sample size was 232 and 157, respectively , while the other sample sizes were below 60.In the included studies, 22 unique games were used for attention rehabilitation. Lumosity , Brain Age (Dr. Kawashima's Brain Training) , and MoHRS  were the most commonly used games. Moreover, 9 (40%) games were developed by the authors of the articles, 10 (45%) games by a commercial group, and 3 (13%) by other scientific groups. The included games had a variety of platforms. The PC application platform was the most frequent , followed by Kinect console , web application , augmented reality system , Nintendo console , PlayStation 2 , tablet application , and VR system .Video game genre refers to categories of games with similar gameplay characteristics, usually not defined by the story and the setting (unlike cinema) but by how the player interacts with the game . Genres In this section, we will briefly describe the features of the games included in the study. All the games along with some of their features are listed in FarmerKeeper is a brain-computer interface video game developed by Mercado et al. to support neurofeedback training for children with autism spectrum disorder . NeurofeDr. Kawashima Brain Training for the Nintendo Switch is the fifth entry in the Brain Age puzzle video game series. It is based on research by neurologist Ryuta Kawashima whose avatar guides the player throughout the game. The Italian version of the game was used in the study by De Giglio et al. . The minLabyrinth includes a little man moving in the maze to reach the goal. The game character is controlled with a joystick by the gamer. The level of difficulty changes according to the task. The game consists of two tasks: diamond task and snake task. Each task has eight difficulty levels on a continuum from lower (level 1) to higher levels (level 8). The purpose of the game character depends on the nature of the current task. In DT, the man must collect diamonds that are randomly distributed in the play area. In ST, he must avoid being caught by a snake and reach the shelter house which appears in a random place.Lumosity includes 50 games, 10 of which are specifically related to attention . In the included studies that have used the Lumosity package, different minigames have been utilized. Here, we provide a brief description of the games related to attention only. Assist Ants is designed to challenge your divided attention. You need to ensure the safety of each ant by helping it avoid collisions. Feel the Beat practices a sense of timing and rhythm. You have to rely on audio cues and use your sense of rhythm to match the beats in each experiment. In Skyrise, the goal is to work on your field of vision. In this game, several squares with numbers inside them appear. You have to memorize all the numbers and select them in ascending numerical order. The main goal of Eagle Eye is to improve your peripheral vision. You need to focus on the white circle in the middle and memorize the symbol or number that appears there. The goal of Playing Koi is to feed all the fish in the pond only once. In Trouble Brewing, you have to prepare a certain number of coffee orders in 2 minutes. In Train of Thought, you must guide each train to the matching station by switching the route keys. In Lost in Migration, the herd stays at one point and your task is to determine the path that the middle bird is facing. In Star Search, players must quickly find a unique object among a set of items that have the same shape, color, movement, and texture.Captain's Log marketed by Brain Train Corporation is a comprehensive suite of computer cognitive learning games consisting of more than 2,000 computer-based exercises targeting 20 cognitive skills. Training modules are presented as games in which students' performance is recorded and points are earned based on performance accuracy.Rayman Raving Rabbids includes 75 minigames and has two modes of play: story mode and score mode. In the story mode, the game follows 15 days of Rayman's imprisonment by the Rabbids. Every day, Rayman must do at least three trials. In the score mode, players can repeat previous trials to improve their scores.Kinect Sports Ultimate Collection simulates 13 sports: basketball, soccer, American football, bowling, beach volleyball, table tennis, boxing, golf, tennis, skiing, darts, baseball, and track and field. To improve performance, songs and comments are used to help control and play the games.AR-Therapist is a simulated augmented reality (AR) environment using a simple game. The game simply simulates two balls in 3D; one is the target ball and the other is not. The player must hit the ball at a specified time which, if correct, will add to the value of the correct shots. Otherwise, the value is added to the errors.CogARC uses the AR interaction technique and manipulation of tangible physical objects (cubes) for cognitive screening and training. This game includes 6 minigames. Game mechanics include challenges, competition, feedback, and rewards. The gameplay structure offers two modes: free and linear. The player can play the minigames freely (free mode), in any order and at the desired levels, or play all the minigames in a predetermined order (linear mode). The minigames include Shape Match in which similar shapes should be matched, Color Match where you have to match the meaning of one word with another word's color, Sum Tower that uses numbers to create the desired sum, Building Blocks where you should find the answer to simple arithmetic calculations, Pattern Memory where you have to memorize and recreate a 3 × 3 matrix pattern of colored tiles, and Word Game where words related to a specific topic must be found.Medal of Honor: Rising Sun (MoHRS) is a first-person shooter video game, the fifth in a series of Medal of Honor released by EA Game. Rising Sun is set in World War II during the Pacific War and has single and multiplayer capabilities.The VR-based serious game application comprises several daily life activities such as buying several items, finding the way to the minimarket, finding a virtual character dressed in yellow, and recognizing outdoor advertisements, devised to train cognitive functions.The Brain Powered Games (BPG) package includes Butterfly, iSpy, Stampede, Whacky Animal, and Gone Fishing. Butterfly is a simple game in which a butterfly flies on the screen and the player must use a mouse or other input devices to move the butterfly when it stops moving at a random location. iSpy is a memory game that works based on a common learning and memory pattern. The player is asked to watch a scene. After a brief display, the image is removed with a short delay and then represented, and the player is asked to click on the new item(s) that were absent in the previous image. In Stampede, the player sees a special animal to be memorized. Then, a group of animals appear spinning on a computer screen, and the player has to click only on the animal that was originally presented. In the Whacky Animal training program, the player is shown animals that must be memorized; as the animals appear randomly on the screen, they must be clicked or touched before disappearing behind the screen. In Gone Fishing, the player has to fish by following the bobber and clicking on it.In Duckneglect, the player is told to tap one or more objects belonging to a particular class (targets) that appear on the screen in a virtual scenario and to avoid distractions with the hand contralateral to the neglected space. The goal of this game is to guide players through visual search tasks.MeMo is divided into two parts, and the first part involves memory. The second part involves flexibility and mental attention, which includes the following three activities: Arrows for processing speed, inhibitory control, and mental flexibility training; Tricky Cards for working memory training; and Jumping Squares for reaction anticipation and inhibitory control training.BrainHQ includes 29 exercises that cover six areas of cognition, including memory, attention, speed, people skills, navigation, and intelligence.Video game tasks involves two types of tasks to train attention: the flow task and the control task. These tasks have the same content, except that the flow task is designed by increasing the difficulty of the task according to the patients' skills and providing clear goals and quick feedback on the score. The task includes Square, Click Number, and Tower. In the Square task, patients must control a central blue square with the mouse and prevent red squares from entering the right, left, top, or bottom of the screen. If the squares coming towards the blue square are black, patients get points for hitting them. In the Click Number task, patients must click and delete disks in numerical order. In the Tower task, blocks of three colors are randomly stacked. Patients should click and delete the right, left, or center of the block based on its color as soon as possible. The removal time of all the blocks is calculated.Caribbean Quest (CQ) is composed of five cognitive games: Scuba, Submarine, Wave, Pirate Delicatessen, and Squidditch. Scuba and Pirate Delicatessen are working memory games, Submarine and Wave are sustained attention games, and Squidditch is a selective attention game. Submarine and Wave are similar in cognitive tasks but different in terms of gameplay. Submarine is a static environment in which the player's only control is the selection of fish from the middle porthole, while the Wave allows the user to navigate an avatar in an ocean.Brainastic includes 17 minigames, four of which are specific for attention. In Conveyor Belt, to learn versatility, you have to change the conveyor sorter and collect items with a specific color. In Spot the Difference, you need to find a unique insect to teach attention and the ability to filter information. In Film Collector, the film should be selected with a specific color or pattern to teach the immediate reaction to move objects. In Honey Haunters, to teach attention and the ability to filter information, you need to determine the correct number continuously over a short period.RehAtt™ uses a 3D VR game environment to combine visual scanning training and multisensory stimulation. The hardware creates a virtual 3D world. The feeling of real touch and guidance is provided by a robotic pen and through vibrotactile feedback.Video game therapy (Kinect Adventures and Kinect Sports) encompasses a wide range of physical activities. Kinect Adventures using full-body movement allows the player to participate in a variety of minigames. Kinect Sports is a collection of six sport simulations and eight small games designed to demonstrate the capabilities of Kinect motion. The six sports include bowling, boxing, athletics, table tennis, beach volleyball, and union football.In Space Fortress, the player uses the joystick to steer a spaceship in an environment without friction and shoot the rocket into the space castle to destroy it; meanwhile, mines keep appearing on the screen.VR-based games include the following: (a) Carnival Games: Monkey see Monkey  and (b) Kinect Adventures (Space Pop and River Rush).In addition to attention measures, some studies also evaluated other cognitive domains such as executive functions, memory, and perception. Here, we only present the measures related to attention. Of 46 tools used in the studies, five used cross-modal oddball attention task , 73, 84,This study identified and categorized serious computer games used for attention rehabilitation and assessed the effects of these games. Game categories were presented based on game genres and different platforms. To the best of our knowledge, this was the first review on this subject. Bogdanova et al.  conducteUpon examining 3937 articles, 30 articles and 22 unique games were included. Seven games were based on personal computer (PC) , 72, 77,Out of the 73 outcome measures, 30 showed significant improvement and only one showed significant deterioration . FurtherThe lack of long-term follow-up was another problem. As observed in the study by Ballesteros et al. , the resThe reviewed studies used different tools to measure attention and its subdomains. Some tools can be applied to all cognitive domains, while some are specific to the domain of attention or its subdomains. There is no standard for measuring attention, and this necessitates a comprehensive and appropriate standard for this purpose. Another important point in game design is the role of scientific teams in game design. Other studies emphasize the participation of therapists and scientific teams in the design process , 36. TheDue to the insufficient RCT studies and the existence of various measures, it was not possible to perform a meta-analysis on the data. Moreover, the control groups greatly differed. For many games, no clinical trial was performed. There were also many articles on general cognitive rehabilitation in which attention rehabilitation was a subscale. Thus, the search was very comprehensive and we tried to overcome this limitation by conducting a more comprehensive search and excluding irrelevant articles.As mentioned in the introduction, attention deficit disorder is usually associated with other cognitive impairments, and each of these deficits may have a positive or negative effect on the other. Perhaps it would have been better if this study had evaluated all these cognitive deficits together, but due to their great complexity and diversity, this was not possible in the study. Therefore, because attention deficit is fundamental and rehabilitation and improvement can help promote other cognitive deficits and reduce disability, we focused only on the area of attention deficit . The funIn this systematic review, we reported game-based computer technologies for attention rehabilitation and assessed the effects of these games. In 19 out of 26 articles measuring the criterion of attention, at least one significant improvement was reported; therefore, it can be concluded that games created for attention rehabilitation are effective and patients and therapists can use the significant benefits of these games to rehabilitate attention deficits. However, to prevent bias, factors such as the variety of criteria and differences in their measurement, small sample size, lack of accurate evaluations of clinical trials on games, absence of scientific teams, lack of long-term follow-up, the existence of different control groups, and not including active groups for comparison should be considered when designing, developing, and using game-based systems. On the other, most of the games found in our study are presented on PC and virtual reality platforms, and for the benefits of portability and continuity of use, we suggest that more games be made for portable platforms such as mobile and tablet.