Editorial on the Research TopicInsights in interventions for rehabilitation: 2023With the rapid advancement of innovative technologies and evolving theories of functional recovery, the field of rehabilitation interventions has witnessed remarkable progress. We are now experiencing a greater shift toward evidence-based, theory-driven, technology-assisted, remote, or novel in-person rehabilitation interventions. This paradigm shift has the potential to lead to improved recovery outcomes and better quality of life for patients living with disabilities, sequelae of injuries, and various medical conditions.In recent years, clinical rehabilitation research has investigated several innovative technologies or applied existing technologies and treatments to novel situations. These include home-based digital technology and/or wearable devices , 2; homeFrontiers in Rehabilitation Sciences. This collection represents a compact compilation of new insights, recent advances, and future perspectives in the field of rehabilitation interventions. Over the past year, our Research Topic accepted five articles that cover a range of interventional approaches and rehabilitation topics, such as a new app-supported executive function training for adults with traumatic brain injury or post-traumatic stress disease; correlation of self-rated balance ratings with kinematic data from wearable research-grade posturographic sensors, an explanatory theory for implementation of research, a new method of non-invasive brain stimulation, and electro-acupuncture for enhanced recovery after surgery. We believe that this Research Topic provides a sample of the latest developments in rehabilitation interventions.We are pleased to announce the publication of our Research Topic titled “Interventions for Rehabilitation 2023”, published in Shiba et al. conducted a case study exploring the therapeutic mechanisms of bihemispheric transcranial direct current stimulation (tDCS) on improving distal upper limb function in a patient with subacute stroke. The study showed greater improvements in upper extremity function, corticospinal tract excitability, and muscle activity patterns after bihemispheric tDCS compared to anodal tDCS. The case study exemplifies the integration of interhemispheric mechanisms post-stroke and neuromodulatory technology into clinical research.Waid-Ebbs et al. focused on an executive training protocol , in Veterans with chronic mild traumatic brain injury and post-traumatic stress disorder. The authors complemented ten in-personal training sessions with a Veteran's Task Manager, a Smartphone application. After the training, participants experienced significant improvements in executive function and community participation. The study demonstrated the feasibility of using digital technology for remote rehabilitation, in addition to therapist-led rehabilitation interventions.Bulley et al. conducted a qualitative analysis of the PEDAL  trial, addressing questions relating to trial feasibility and long-term intervention implementation. They interviewed research participants enrolled in the PEDAL trial as well as health care and research staff. The in-depth thematic analysis led to a novel explanatory theory with relevance for evaluation of rehabilitation interventions, elaborating on complex interactions between different aspects of intervention delivery and trial implementation within the clinical environment.Ferris et al. identified the relationship between physical therapists' ratings of balance intensity , patients' self-assessments of balance intensity, and quantitative posturographic measures when older adults or participants with vestibular disorder-related balance concerns performed standing balance exercises. The results suggested that patients can more easily distinguish two levels of balance ability (higher-lower) instead of five levels of balance ability during their self-ratings; and that self-ratings and trunk kinematic measurements using inertial measurement units may assist in the physical therapists' assessments of the patients' balance performance, especially when visual assessment is difficult .Mao et al. provided a review of the potential value and feasibility of electro-acupuncture (EA) for enhanced recovery after surgery. Enhanced recovery refers to a series of optimal perioperative interventions to reduce psychological and physical traumatic stress in order to facilitate rapid recovery of patients, reduce the risk of readmission and death, and decrease costs. EA can attenuate the inflammatory response and stress response, ease anxiety and depression, protect cardiovascular and cerebrovascular function, help postoperative intestinal function recovery, and shorten hospital stay, thereby improving perioperative efficacy. In sum, this review provides evidence-based data to support the notion that EA can play an increasingly important role in rehabilitation and treatment in the future.The articles published in this Research Topic describe a small sample of recent developments of novel interventions targeting motor function, cognition, balance, as well as general recovery in patients living with subacute stroke, chronic mild traumatic brain injury, and post-traumatic stress disorder, chronic kidney disease, older adults, adults with vestibular disorder-related balance concerns, or who undergo surgery. The articles highlight the integration of various technologies, including new ways of using non-invasive brain stimulation, digital technology, and complementary and integrative practices, as part of rehabilitation assessments or as interventions. Moreover, one article highlights the use of qualitative methods to reflect on trial feasibility and implementation of interventions.In sum, despite the small number of published papers, this Research Topic encompasses a heterogeneous sample of new insights, novel developments, current challenges, latest discoveries, recent advances, and future perspectives in the field of interventions for rehabilitation. As this is an ever-evolving field, we hope that this Research Topic will engender new research ideas and collaborations leading to further developments and discoveries in the field of rehabilitation interventions and assessments.


Rehabilitation is considered one of the elements of universal health coverage, emphasizing its importance for every person in need throughout the life course. Nurses play a pivotal role in the rehabilitation team as they possess the competencies to help individuals manage health problems and maximize potential well-being. Yet, little is known regarding knowledge of this subject among nursing students, as well as regarding their attitudes, thoughts, and professional behavior. This study aimed to explore: (a) Sophomore students’ attitudes, feelings, thoughts, and professional behavior toward rehabilitation patients; and (b) Differences in the research variables as affected by students’ previous exposure to rehabilitation patients.A cross-sectional survey design among sophomore nursing students. A questionnaire was distributed through a commercial internet survey provider  before the beginning of a mandatory course on “nursing rehabilitation”, introduced for the first time in 2022 in all Israeli universities. Students were divided into three groups according to their previous exposure to rehabilitation patients: no professional or personal previous exposure to rehabilitation patients; previous professional or personal exposure to rehabilitation patients; and previous exposure to rehabilitation patients both in one’s professional and personal life. The study adhered to the STROBE guidelines.H = 22.06, p = 0.006, H = 23.86, p = 0.03, respectively). No other statistical differences were observed between the groups.The sample consisted of 122 participants. Significant differences were found between the groups by their previous exposure to rehabilitation patients. Participants with no previous exposure to rehabilitation patients were found to have lower self-perceived capability to care for rehabilitation patients and more negative professional behavior toward rehabilitation patients and their families compared to the other two groups (The findings emphasize the importance of exposing students to the field of nursing rehabilitation and to the care of rehabilitation patients. Exposure to nursing rehabilitation specifically during one’s studies, through theoretical learning and clinical experience, can promote positive attitudes, professional values, and positive professional behavior toward these patients and their families.The online version contains supplementary material available at 10.1186/s12912-023-01616-y. Rehabilitation is considered one of the elements of universal health coverage (UHC), meaning that rehabilitation services must be available worldwide for every person in need . The terThe Association of Rehabilitation Nurses ARN 2014) states that “rehabilitation nursing is precisely the response to functional impairments and deterioration of individuals” . Since t states tIn September 2020, for the first time, the Israeli Ministry of Health recognized four nurses as practitioner nurses in rehabilitation. In March 2021, the Director of Nursing at the Ministry of Health published guidelines for the authorization of nurse specialists in rehabilitation. The guidelines stated: “The nurse specialists in rehabilitation is a key professional figure who helps people deal with long-term health problems, reduces dependency, and maximizes potential” . This coStudies conducted in the UK, Denmark, Finland, and Norway among nurses employed in rehabilitation facilities revealed that nurses thought that their pre-licensing education had not provided them with adequate knowledge and skills to prepare them for their role in rehabilitation. Pre-registration education provided only a basic introduction to rehabilitation. This contrasted with acute nursing care, for which pre-registration studies provide a good background and preparation , 10. A sRegarding nursing students, the literature review revealed a paucity of studies on the subject worldwide, where the existing research focuses mainly on students’ attitudes toward people with disabilities rather than specifically on rehabilitation. It is important to note that most of the studies were conducted about two or three decades ago. For example, Thompson et al. (2003) explored whether a change in curriculum and clinical experience affected nursing student attitudes toward disabled persons. Students’ attitudes were significantly more positive after completing their senior year. The findings suggest that education and exposure to individuals with disabilities positively affected nursing students’ attitudes toward individuals with disabilities .It may be concluded that nursing plays a vital role in the therapeutic process of rehabilitation patients. However, nurses lack formal academic knowledge of rehabilitation. Considering the current gap in the literature regarding the treatment of rehabilitation patients, the present study examined attitudes, feelings, thoughts, and professional behavior toward rehabilitation patients among nursing students, in preparation for an academic course on the role of nursing as part of a multi-professional team caring for rehabilitation patients.The aim of the study was to explore: (a) Sophomore students’ attitudes, feelings, thoughts, and professional behavior toward rehabilitation patients; and (b) The differences in the research variables as affected by students’ previous exposure to rehabilitation patients.The current study utilized a descriptive, cross-sectional design. The study adhered to the STROBE guidelines.All second-year undergraduate nursing students in the Baccalaureate and Accelerated programs at a major Israeli university (245 students) were invited to participate in the study. Second-year students in the two programs were selected for participation in this study since they had already completed at least two clinical placements in acute care settings in hospitals and experienced basic nursing care interventions.The sample size was calculated using G*Power software . To condThe research instrument was a structured questionnaire including three sections:A) Participants’ sociodemographic data and previous exposure to rehabilitation patients. Sociodemographic data included age, gender, country of birth, ethnicity, and marital status. Two additional items assessed the participants’ prior exposure to rehabilitation patients: (1) Have you previously cared for a rehabilitation patient? (yes/no); (2) Do you have a relative undergoing a rehabilitation process? (yes/no)B) Attitudes toward rehabilitation patients and rehabilitation nursing. The research team developed this section, inspired by the capability, opportunity, and motivation behavior (COM-B) framework [ramework . The COMramework , such asPerceived physical and psychological capability to care for rehabilitation patients included the knowledge and skills required to work with these patients, for example: “I know how to work according to the principles of rehabilitation nursing”. Participants were asked to rank their agreement regarding each item on a 5-point scale from 1  to 5 (strongly agree). A higher score means higher perceived capability to care for rehabilitation patients. The internal consistency based on Cronbach’s alpha was 0.86.Perceived professional opportunity in rehabilitation nursing, including the cognitive and emotional process needed for analytical decision making. For example, “Treating a patient with a rehabilitation potential is a professional challenge for me.” Responses were given on a 5-point scale from 1  to 5 (strongly agree). A higher score means a higher perception of the professional opportunity in rehabilitation nursing. The internal consistency based on Cronbach’s alpha was 0.73.Students’ motivation to care for rehabilitation patients. This means an external factor that motivates the students and makes rehabilitation care a possible behavior. A sample item is, “I am proud of the contribution of nursing in the field of rehabilitation.” Responses were given on a 5-point scale from 1  to 5 (strongly agree). A higher score means higher motivation to care for rehabilitation patients. The internal consistency based on Cronbach’s alpha was 0.72.C) Students’ feelings, thoughts, and professional behavior toward rehabilitation patients: This section of the questionnaire was adopted from the validated Multidimensional Attitudes Scale (MAS) for people with disabilities [bilities . The secbilities .The original questionnaire was adapted to the present study, and the vignette dealt with a nurse caring for rehabilitation patients in a hospital. The vignette presented the participants with a short case description of a rehabilitation patient hospitalized in a rehabilitation unit after experiencing a stroke. The patient was described as having a low rehabilitation potential. His family visits him frequently and demands that the attending nurse and physician not stop the rehabilitation process. Immediately following, participants are asked to reply to three sections based on the earlier description: (a) possible feelings of the nurse in the vignette toward the patient, (b) possible thoughts of the nurse in the vignette toward the patient, and (c) possible professional behaviors performed by the nurse in the vignette concerning the patient . Participants were asked to rank the likelihood that the nurse would feel each of the feelings toward the patient, on a 5-point Likert scale from 1  to 5 (very likely). Factor analysis of this part indicates that it is divided into two sub-scales: negative feelings  and positive feelings .Thoughts - This section contains a list of five positive thoughts the nurse in the vignette may think regarding the patient . Participants are asked to rank the likelihood that the nurse would think each of the thoughts toward the patient, on a 5-point Likert scale from 1  to 5 (very likely). A higher score means more positive thoughts regarding the rehabilitation patient. Cronbach’s alpha = 0.70.Professional behavior – This section contains a list of five negative professional behaviors the nurse in the description might perform . Participants are asked to rank the likelihood that the nurse would perform each of the professional behaviors toward the patient, on a 5-point Likert scale from 1  to 5 (very likely). A higher score means more negative professional behavior toward the patient. Cronbach’s alpha = 0.78.The whole questionnaire underwent content validation by two senior rehabilitation practitioner nurses. Each one of them examined the questionnaire alone and later a joint meeting was held with the research team. A discussion was conducted, and the vignette and the items were corrected with complete agreement.All second-year undergraduate nursing students in the university nursing program were approached two weeks before the “Nursing rehabilitation” course commenced, during March-June 2022. The study was conducted using the format of a commercial internet survey provider . A link to the online questionnaire appeared on a short explanatory page that presented the research aims. The page was posted in a social media group for second-year students, by a research assistant who was not an instructor of these students. The study received the approval of the university’s ethics committee (#0004421-1). A link to the Qualtrics code was sent to all sophomore students via their closed media groups. The link to the online questionnaire appeared on a short explanatory page that clarified the research purposes. Participants were assured that responses to the questionnaires would be anonymous and that their confidentiality would be maintained. Consent was assumed by submission of the questionnaire. Only students who agreed to participate and gave their informed consent could access the questionnaire.Based on the two questions regarding previous exposure to rehabilitation patients, the participants were divided into three groups as follows: no previous exposure recoded = 0, defined as group A; previously treated rehabilitation patients or having known relatives in the rehabilitation process recoded = 1, defined as group B; both previously treated rehabilitation patients and having known relatives in the rehabilitation process recoded = 2, defined as group C. Descriptive statistics were used to compare the sample characteristics of the three groups.H test was conducted to explore the differences in the variables among the three groups. Pairwise comparisons were performed using Dunn’s procedure (for the post hoc test) with Bonferroni correction for multiple comparisons, and adjustment p-value was calculated. The data were analyzed using the SPSS-27 statistical package . Statistical significance was considered at p < 0.05.The Kruskal-Wallis Altogether, 161 questionnaires were returned, but 39 were excluded as they had not been fully completed (response rate 49.8%). Most of the participants were female (83.1%), with a mean age of 26.5 (SD = 6.06), Jewish (80.0%), and secular (63.8%) (Table p < 0.001). This means that the greater the negative feelings rehabilitation patients evoke, the greater the negative professional behavior toward rehabilitation patients.A Spearman correlation test was conducted to explore the association between the research variables Table . The maip = 0.003. Subsequently, post hoc pairwise comparisons using Dunn’s procedure with Bonferroni correction for multiple comparisons revealed statistically significant differences in the scores for participants’ attitude to their capability between Groups B and A. Group B participants had a statistically significantly higher capability to care for rehabilitation patients compared to participants in group A  but other group combination.Table p = 0.03. Subsequently, post hoc pairwise comparisons using Dunn’s procedure with Bonferroni correction for multiple comparisons revealed statistically significant differences in the scores for negative professional behavior between Group A and Group C. Group A participants had statistically significantly higher scores for negative professional behavior compared to participants in Group C , but no such difference was found for any other group combination.The Kruskal-Wallis test revealed that the median scores for negative professional behavior of participants in the different groups were statistically significantly different, H = 6.49, No other significant differences were observed.The current study aimed to explore sophomore nursing students’ attitudes, feelings, thoughts, and professional behavior regarding rehabilitation patients. The findings suggest that students with no previous exposure to rehabilitation patients have a lower self-assessment of their capacity to care for rehabilitation patients and higher negative professional behavior toward rehabilitation patients and their families. These findings highlight negative professional behavior by students who were not exposed to these patients at all and indicate a professional value gap. Students display professional behavior not expected of sophomore nursing students , and this issue should be examined in depth. Our findings point to the need to expose students to the care of patients in the process of rehabilitation and expand and deepen the knowledge base on this topic. Developing students’ knowledge and providing them with professional opportunities to meet and care for these patients and to encounter the rehabilitation process can promote positive attitudes towards the field, positive feelings and thoughts, and positive professional behavior. These recommendations are enhanced and receive added importance in light of the increase in life expectancy in developed countries , the impA significant difference was found in students’ attitudes regarding their perceived capability to care for rehabilitation patients: students who had previous experience with rehabilitation patients in their professional or personal life had a significantly more positive attitude regarding their capability to care for rehabilitation patients than their peers who had no professional or personal previous exposure to rehabilitation, which means that exposure to rehabilitation patients may affect students’ attitudes toward the care of these patients. This finding is congruent with earlier findings among nursing students in other clinical fields, emphasizing the central role of exposure and interaction with complex patients on students’ attitudes. Increasing the quantity and quality of student’s experience can impact their confidence in their knowledge and skills regarding the capability to care for complex patients , 23, 24.With regard to negative professional behavior, only students who had previous exposure to rehabilitation patients in their professional and personal life reported low perceived negative professional behavior, compared to the other two groups. This finding should receive the attention of nurse educators as it points to the need to strengthen and emphasize professional values and professional behavior towards patients. Sümen et al. (2022) found a low positive association between nursing students’ positive professional attitudes and caring behavior . NegativGroup C participants in the current study, who had been previously exposed to rehabilitation patients and were familiar with rehabilitation patients, were older than the other two groups and expressed lower negative professional behavior toward rehabilitation patients. Similar findings were reported in an integrative literature review, indicating an association between age and the nurse’s professional values. Notably, an increase in age was associated with higher positive professional values. Other factors described in this literature review were the nurse’s level of education and learning activities . In the The current study has several limitations related to the research design and tools. It employed a convenience sampling drawn from a single university and was based on self-reports. Although this university has the largest nursing department in Israel, this might limit the generalizability of the findings to the entire population of second-year nursing students. This study could be improved by drawing participants from several universities in the future. The questionnaire included only closed-end questions. Adding more open questions and interviews with students and educators could have provided more information and a deeper understanding of students’ perceptions and comprehension of the subject of rehabilitation.The sections referring to thoughts and professional behavior considered only positive thoughts and negative professional behavior, as recommended in the original tool. In the future, we recommend adding negative thoughts and positive professional behavior to the tool in order to explore the full range of the phenomena. The vignette used in the current study dealt with one case of nurse-patient-family encounters. Adding more clinical scenarios may uncover different and more detailed findings than found in the current study. In addition, the MAS questionnaire was adapted for rehabilitation patients. Content validation was conducted, and internal consistency was calculated. However, it is recommended to validate the questionnaire in additional statistical ways. Finally, the response rate in our study was less than 50% and there are no details regarding the students who did not respond to the study.Students’ exposure to rehabilitation patients and expanding their knowledge base on the subject can promote positive attitudes, feelings, thoughts, and professional behavior toward this field. The research findings highlight the need to expand and deepen students’ knowledge in the field of rehabilitation to promote positive attitudes and strengthen professional values and positive professional behavior. Moreover, nursing professional values and professional behavior toward rehabilitation patients should be refined and strengthened.Below is the link to the electronic supplementary material.Supplementary Material 1


To compare vitreous angiomosaic images (VAMIs), obtained by widefield swept-source optical coherence tomographic angiography (wfSS-OCTA) and the image of fluorescein fundus angiography (FFA) in the identification of retinal neovascularization (NV) in patients with diabetic retinopathy (DR).In this prospective observational study, severe non-proliferative diabetic retinopathy (NPDR) or proliferative DR (PDR) patients were included. All patients underwent FFA and wfSS-OCTA. The number of NVs identified by wfSS-OCTA VAMIs using five fixations 12 × 12 mm montage scans and the resembling FFA images were compared.p = 0.203), with excellent agreement (intraclass correlation coefficient = 0.941).Fifty-three eyes of 29 patients were enrolled. NVs were detected in 25 eyes by using FFA, including 9 NVs of the disc (NVDs) and 72 NVs elsewhere (NVEs), and in 29 eyes by OCTA, including 11 NVDs and 90 NVEs. The detection rate of NV and NVD of OCTA was comparable to that of FFA (p > 0.05), and the level of agreement was excellent . Using FFA as the gold standard, the sensitivity for detection of NV by OCTA was 100.0%, specificity was 85.7%, the positive-predictive value was 86.2%, and the negative-predictive value was 100.0%. Compared with FFA, OCTA was superior in terms of the number of NVEs identified (p = 0.024). When we excluded images of patients treated with anti-vascular endothelial growth factor (VEGF) intravitreal therapy for < 3 months, OCTA was comparable to FFA in terms of the number of NVEs discovered (WfSS-OCTA is an independent non-invasive alternative to FFA for NV discovery, NVD detection, and individual NVE identification, particularly in patients with PDR who have a history of prior treatment with anti-VEGF. Diabetic retinopathy (DR) is the leading cause of blindness among the global working-age population –3. ProliFluorescein fundus angiography (FFA) has been used for identifying NV for over 50 years –11; howeIn contrast, optical coherence tomography angiography (OCTA) is a non-invasive and safe procedure, providing clear three-dimensional (3D) images of blood vessels and structures without the need to use dye agents. Generally, OCTA is used to diagnose macular or optic disc diseases and as an alternative to FFA , 13. WidWfSS-OCTA using 15 × 15 mm montage scan plus ultra-widefield color fundus photography may offer a less invasive alternative to FFA for DR diagnosis . WfSS-OCHere, we conducted a prospective study to compare five-fixations of 12 × 12 mm scan montage VAMI up to 17.5 × 23.5 mm of the retina surface obtained by wfSS-OCTA with resembling FFA images for the detection of NV.This prospective observational study was approved by the ethics committee of Shandong Provincial Hospital  and was performed in accordance with the principles of the Declaration of Helsinki. Informed consent was obtained from all patients. Severe non-proliferative DR (NPDR) or PDR patients with type 2 diabetes mellitus (DM) based on clinical diagnosis were consecutively included in this study at Shandong Provincial Hospital from September 2020 to January 2021. The exclusion criteria were as follows: patients with severe media opacities , fixation difficulty, acute angle-closure glaucoma, concomitant chorioretinal diseases, unavailable FFA images, unavailable automatic image montage, poor image quality, and a history of vitrectomy. All enrolled patients underwent routine ophthalmologic examination, FFA , and wfSS-OCTA . Clinical information, including diabetes duration and DR severity, was collected from the medical records.WfSS- OCTA uses a swept-source laser with a central wavelength of 1,050 nm and a bandwidth of 100 nm at a scanning speed of 200,000 A per second. It provides 3D images of vessels and structures with an axial resolution of 5μm, digital resolution of 2.0μm, and scanning depth of 2.7 mm. This study used the 12×12 mm 1024×1024 R2 angio scan protocol in five prediction fixations  for each patient. Each scan was comprised of 1024 B-scans with 1024 A-scans per B-scan, repeated twice at each fixation. The 12×12 mm scans of the fundus obtained at five fixation points were auto-merged into different slabs of widefield AMI, with a scan area of up to 60°×80 (17.5 × 23.5 mm).The VAMI showed the hyper-reflected blood flow within a defined volume between the outer boundary 5μm anterior to the internal limiting membrane (ILM) and the inner boundary at the top of the vitreous cavity in the B-scan, and was the main image used to detect NV Fig. A, B. NV FFA was performed as a standard protocol after an intravenous injection of 5 mL of 10% sodium fluorescein into an antecubital vein. Images were captured digitally and compressed into high-quality JPEG files. For evaluation, the FFA images were transferred to Adobe Photoshop software , spliced according to the direction of the blood vessels, and cropped to the same location and size as that on wfSS-OCTA RAMI, which was labelled as “resembling FFA image” Figs. A, E. On p-value of < 0.05 was considered statistically significant. Statistical analysis was performed using SPSS V. 24.0 .The normally distributed continuous variables are presented as mean ± standard deviations. The detection rate of NV/NVD was compared between wfSS-OCTA VAMIs and resembling FFA images by means of McNemar’s test. Levels of agreement were calculated using Cohen’s kappa test. Kappa was characterized as follows: > 0.75 as excellent, 0.40–0.75 as fair to good, and < 0.40 as poor. Resembling FFA images were used as the gold standard. The sensitivity, specificity, and accuracy for discovering NV with wfSS-OCTA VAMI were calculated. The number of NVEs identified on wfSS-OCTA VAMIs and on FFA images were compared using the nonparametric Wilcoxon signed-rank test. Levels of agreement were calculated using the intraclass correlation coefficient (ICC). The ICC was characterized as follows: > 0.75 as excellent, 0.40–0.75 as fair to good, and < 0.40 as poor. A normal, two-tailed Fifty-three eyes of 29 patients (16 men and 13 women) were included in the study. The average age of the patients was 51.4 ± 9.5 years, and the average diabetes duration was 9.2 ± 5.2 years. The mean best-corrected visual acuity (BCVA) was 0.42 ± 0.40 logarithm of the minimum angle of resolution (LogMAR). The mean intraocular pressure (IOP) was 16.3 ± 2.4 mmHg. All enrolled patients were diagnosed with type 2 DM. Twenty-eight (52.8%) eyes were treatment-naïve, and 25 (47.2%) had a history of treatment before imaging . Twenty-three eyes of patients had concomitant diabetic macular edema, and one eye of one patient was diagnosed with DR secondary to NVG with eye drop-controlled IOP. All of these eyes underwent wfSS-OCTA and FFA examinations. The baseline characteristics of these patients are summarized in Table p = 0.125). The level of agreement was excellent .In 29 (54.7%) eyes, NV was detected by OCTA, and in 25 (47.2%) eyes, NV was detected by FFA , the specificity was 85.7% , the positive-predictive value was 86.2% , the negative-predictive value was 100.0% , and the accuracy was 92.4%.p = 0.625). The level of agreement was excellent  eyes, NVD was detected using OCTA, and in nine (17.2%) eyes, NVD was detected using FFA, of which NVD in eight (15.1%) eyes was confirmed by both FFA and OCTA examination (Table 0.8% eyesp = 0.024 < 0.05). Ninety and 72 NVEs were identified using OCTA and FFA, respectively (Table p = 0.203). The level of agreement was excellent ; 79 NVEs were detected using OCTA, and 71 NVEs were detected using FFA . The level of agreement was excellent . Twenty-seven (50.1%) eyes were diagnosed with PDR using merged FFA, and 25 (47.2%) eyes were diagnosed with PDR using resembling FFA (Table p = 0.001). The level of agreement was excellent . Of the 104 NVEs in 53 eyes, 32 NVEs were distributed outside the resembling FFA image; however, in only three eyes, all the NVEs were located outside the resembling FFA images, and in one of these three eyes, an NVD was found within the resembling FFA image. The diagnosis of PDR was affected in only two eyes, in which all NVs were outside the coverage area of the resembling FFA image.Use of resembling FFA images was comparable to use of merged FFA images in diagnosing PDR , the specificity was 100% , the positive-predictive value was 100.0% , the negative-predictive value was 92.86% , and the accuracy was 96.2%.OCTA is a useful tool for identifying the origins and morphological patterns of NV in PDR , 24. Prep < 0.001).NVEs are more likely to be located in the posterior pole than in the far periphery . A studyA pilot study obtained similar results in patients with PDR who underwent anti-VEGF IVT ; the strIn this study, NV was found in five eyes by OCTA, but not by FFA examination. Two eyes showed a large amount of fluorescence leakage, which obscured the features of NVEs, and three eyes had fluorescence leakage at small NVEs, coinciding with a hyper-fluorescence background of retinal photocoagulation scars. With no impact on fluorescein leakage, wfSS-OCTA VAMI may be more sensitive than FFA in detecting NV in patients with poor cooperation, diffuse leakage of abnormal vessels, or minimal dye leakage of NV. Therefore, with 3D flow imaging, even small-sized NV located closely in front of strong fluorescent areas, such as laser scars or retinal blood vessels in FFA, can be easily found on VAMIs, when excluding the blood flow behind the ILM. In addition, the single, auto-stitched wide-angle VAMI (17.5 × 23.5 mm) makes the white NV clear on the black background, which is convenient for the graders to find out NV and reduces the time spent in detecting NV in B scan frame by frame. VAMIs may be useful to detect and monitor NV in clinical practice. Thus, detecting and following-up changes in NV with OCTA VAMI is more advantageous than doing so with FFA for DR patients with a history of previous treatment with anti-VEGF IVT or PRP.NVs from the retinal and optic nerve head that grow into the vitreous cavity and show marked leakage visualized in FFA are the diagnostic hallmarks of PDR , 16. A VAs the eye is a sphere, the resembled eyeball is nearly flat when the scan coverage is small (3 × 3 mm), and the whole retina can be contained in the scan volume. With the expansion of coverage (17.5 × 23.5 mm), the resembled eyeball is nearly hemispherical. If we focus on the central part of the retina, the surrounding parts will bulge out of the scan volume. In our study, more NVEs located at the edge of the scan areas of RAMI were found in resembling FFA images than in VAMIs in two eyes. Usually, VAMI and RAMI have the same scan area. Sometimes, the surrounding parts of VAMI are cut off because they bulge out of the vitreous scan volume, resulting in a smaller scan area than that of RAMI. OCTA could only display the image of the central part of the posterior pole retina in patients with severe myopia, which restricted the use of OCTA in the independent diagnosis of PDR in DR patients with severe myopia. Therefore, the challenge for wfSS-OCTA is not only to expand the scan width but also to increase the scan depth accordingly.The limitations of the current study included the small sample size and that naïve and treated patients were not analyzed separately. To validate our conclusions, it will be necessary to perform a large-scale randomized and multicenter clinical trial.In conclusion, wfSS-OCTA is an independent alternative to FFA for diagnosing PDR, detecting NVD, and identifying individual NVE non-invasively, particularly for patients with PDR who have undergone previous treatment.


Drowsiness associated with sleep loss and circadian misalignment is a risk factor for accidents and human error. The percentage of time that the eyes are more than 80% closed (PERCLOS) is one of the most validated indices used for the passive detection of drowsiness, which is increased with sleep deprivation, after partial sleep restriction, at nighttime, and by other drowsiness manipulations during vigilance tests, simulated driving, and on-road driving. However, some cases have been reported wherein PERCLOS was not affected by drowsiness manipulations, such as in moderate drowsiness conditions, in older adults, and during aviation-related tasks. Additionally, although PERCLOS is one of the most sensitive indices for detecting drowsiness-related performance impairments during the psychomotor vigilance test or behavioral maintenance of wakefulness test, no single index is currently available as an optimal marker for detecting drowsiness during driving or other real-world situations. Based on the current published evidence, this narrative review suggests that future studies should focus on: (1) standardization to minimize differences in the definition of PERCLOS between studies; (2) extensive validation using a single device that utilizes PERCLOS-based technology; (3) development and validation of technologies that integrate PERCLOS with other behavioral and/or physiological indices, because PERCLOS alone may not be sufficiently sensitive for detecting drowsiness caused by factors other than falling asleep, such as inattention or distraction; and (4) further validation studies and field trials targeting sleep disorders and trials in real-world environments. Through such studies, PERCLOS-based technology may contribute to preventing drowsiness-related accidents and human error. Extensive evidence indicates that the percentage of time that the eyes are 80% closed (PERCLOS) increases with drowsiness caused by sleep loss or circadian misalignment during vigilance tests, simulated driving, and on-road driving. However, this is not always the case, such as under moderate drowsiness conditions, in older adults, and during aviation-related tasks. Although PERCLOS is one of the most accurate measures for detecting drowsiness in vigilance tests, it may not always be the most reliable indicator for detecting drowsiness while driving or in other real-world scenarios. Integrating PERCLOS with other physiological or behavioral measures may enable the robust detection of drowsiness in a variety of real-world situations and contribute to preventing drowsiness-related accidents and human error.Multiple factors are involved in “sleepiness,” including sleep loss/sleep restriction , time siet al. for detecting driver drowsiness  ≥3 s) during the OSLER test associated with drowsiness manipulation is shown to be higher than various measures, including slow eye movements, blink parameters, pupil diameter, heart rate variability, and EEG-based measures as demonstrated in Importantly, PERCLOS values during PVT have been shown to be similar in repeated exposures to sleep deprivation, indicating that the PERCLOS response to sleep deprivation is trait-like . This isA method for detecting vigilance deterioration in PVT with greater accuracy than PERCLOS has been reported. A PERCLOS-based algorithm that integrates multiple eye metrics was found to outperform PERCLOS, with ICCs of PVT RT ≥ 300 ms . HoweverValidation of PERCLOS as a measure of drowsiness in operational environments requires both simulated and field studies . Many vaThere are several issues that need to be addressed to increase the efficacy of PERCLOS in detecting drowsiness during on-road driving. First, there are conflicting pieces of evidence regarding the effectiveness of PERCLOS or %TEC in detecting drowsiness after night shifts. Some studies have found that PERCLOS or %TEC increases after a night shift when driving on a simulated course  or durinWhat behavioral parameters are related to PERCLOS during drowsy driving? There is generally robust evidence of a relationship between PERCLOS and measures of lateral position variability  during simulator driving , 89, 100Is PERCLOS more sensitive than other indicators in detecting drowsiness during driving? In vigilance tests, PERCLOS has consistently been shown to be more accurate in detecting drowsiness than other indicators; however, this is not always the case in the driving situation as shown in To overcome the issues of PERCLOS described above, integrating PERCLOS with other physiological or behavioral indicators has been attempted to provide a better estimation of a driver’s state or performance during driving, for example: (1) classifying drowsiness categories into three levels by integrating lane deviation of driving and PERCLOS , 103; .Many studies have shown that PERCLOS increases with sleep deprivation, after partial sleep restriction, at nighttime, and by other drowsiness manipulations during vigilance tests, simulated driving, and on-road driving. However, there are cases in which PERCLOS is not affected by drowsiness manipulation, such as in moderate drowsiness conditions, in older adults, and during aviation-related tasks. In addition, although PERCLOS is one of the most sensitive indices for detecting drowsiness-related performance impairments during PVT or the OSLER test, other indices exhibit superior performance compared with PERCLOS during simulated driving or aviation tasks. Another potential limitation of PERCLOS is that slight differences in the definition of PERCLOS and the presence of multiple measurement instruments may cause variations in PERCLOS values among different studies. Standardization of PERCLOS or validation across multiple studies using a single device to implement PERCLOS-based technology may be useful for clarifying the range of populations, tasks, and situations for which it is an effective measure. Furthermore, PERCLOS alone may not be sensitive for detecting drowsiness-related performance impairment by factors such as inattention or distraction other than falling asleep , 72. The


The upper limb functional index (ULFI) is a widely used self-report outcome measure questionnaire with robust psychometric properties to assess the upper limb musculoskeletal disorders (UL-MSDs). This study aimed to investigate the psychometric properties of the Arabic version of ULFI (ULFI-Ar).n = 46) and responsiveness (n = 27).In this observational study, 139 patients  with various UL-MSD’s, completed the ULFI-Ar, Disability of Arm, Shoulder, and Hand questionnaire (DASH-Arabic), and numeric pain rating scale (NPRS-Arabic). All participants determined the factor structure, and the construct validity. A subgroup of the participants determined test–retest reliability (2:1) = 0.95], measurement error , medium internal responsiveness [Cohen’s d = 0.62 and standard response of mean (SRM) = 0.67], strong external responsiveness DASH-Arabic , and negative strong correlation with NPRS-Arabic .The ULFI-Ar construct validity obtained by the expletory factor analysis as one-factor structure, demonstrated an excellent test–retest reliability [intraclass correlation coefficient (ICCThe ULFI-Ar is a valid, reliable, and responsive self-report questionnaire to assess UL-MSDs in Arabic speaking patients. Musculoskeletal disorders (MSDs) are common complaints encountered by clinicians including physical therapists . The uppOne of the evaluation tools is self-reported outcome measures, which are designed to detect a patients’ health status, function level, and health-related quality of life , 5. FurtThe upper limb functional index (ULFI), on the other hand, has overcome the aforementioned limitations successfully. The ULFI has been used in several countries and translated and validated in many languages including Spanish , French-This is an observational cross-sectional study that was conducted between of March and September 28, 2021 in . The Institutional Review Board of the  approved the study . The study followed the guidelines of the Strengthening the Reporting of OBservational studies in Epidemiology (STROBE)    in a sub2,1] . The meabaseline . The minMx2x1.65 .d) and the standard response mean (SRM) , which supported that the 25 items structure should be reserved.For construct validity, the EFA revealed six factors with Eigenvalues > 1; where only one factor exceeded 10% variance 25.62%) and was presented before the inflection point . The test–retest reliability of the ULFI-Ar was excellent  with an individual range of 95% CI = 0.90 – 0.97. The measurement error from the SEM and MDC90 were 4.43% and 10.34%, respectively.Paired t-tests showed no significant difference between the ULFI-Ar testing and retesting scores . The effect size was medium  and SRM was also medium . The percentage difference between SRM and effect size for the same change measurement on the same participant was 1%. The external responsiveness was strongly correlated with the DASH-Arabic (r =—0.90). A negative strong correlation was found between the ULFI-Ar and NPRS-Arabic .The internal responsiveness of the ULFI-Ar as represented by the paired t-test resulted in significant difference between the baseline and responsiveness scores . This result is in agreement with the studies of the English , Spanishctively] . Howeverctively] .2:1 = 0.95) supports the instrument’s stability. This is comparable with the English [ICC2:1 = 0.98] [2:1 = 0.97] [2:1 = 0.94] [2:1 = 0.93] [2:1 = 0.93] [2:1 = 0.92] [2:1 = 0.91] [2:1 = 0.90] [2:1 = 0.90] [2:1 = 0.72]   [t-test. It is an optimal period for the clinician to detect the patients’ functional status in a short time and to evaluate the intervention outcome [Internal responsiveness measured by Cohen’s  = 0.88]  but lowectively] , 31. ExtThe main strength of this study is that we attempted to investigate all psychometric properties of the ULFI-Ar.. Another strength is that our study recruited participants with acute, subacute, and chronic conditions . A limitThe study showed that the ULFI-Ar is a unidimensional factor and has excellent test–retest reliability, and medium to strong responsiveness. The ULFI-Ar can be used as an appropriate outcome measure in clinical and research setting for Arabic speaking patients with UL-MSDs. Future research is recommended to assess the psychometric properties of the ULFI-Ar in patients undergoing treatments than physical therapy.


The aim of this study is to evaluate the effect of inpatient rehabilitation on pulmonary function in patients recovering from COVID-19, a multifaceted disease caused by the SARS-CoV-2 virus. This aspect of recovery is crucial, as pneumonia associated with this disease can cause lung-function abnormalities with varying degrees of hypoxemia. This study involved 150 patients qualified for inpatient rehabilitation following SARS-CoV-2 infection. Functional assessment of the lungs was performed by spirometry. The mean age of patients was 64.66 (±11.93) years, and the mean body mass index (BMI) was 29.16 (±5.68). The tests showed a statistically significant improvement in spirometric parameters. The rehabilitation program based on aerobic, strength, and endurance exercises improved lung-function parameters in the long term. The improvement in spirometric parameters in patients after COVID-19 may be related to body mass index (BMI). COVID-19 is a multifaceted disease caused by the SARS-CoV-2 virus that affects the respiratory, nervous, cardiovascular, and gastrointestinal systems. It was declared a pandemic by the World Health Organization (WHO) in March 2020 .The lungs are the most common target of SARS-CoV-2 infection. COVID-19-associated pneumonia may cause lung-function abnormalities with varying degrees of hypoxemia, resulting in cough and shortness of breath. Chest computed tomography (CT) and chest radiography show characteristic multifocal, bilateral, patchy opacities or consolidation with interlobular septa and vascular thickening in peripheral lung areas ,5. ApproAbout half of patients recovering from COVID-19 report chronic dyspnea months after the onset of the disease. Respiratory function testing, including spirometry, shows reduced vital capacity (FVC) and total lung capacity (TLC) in COVID-19 patients. Other symptoms include reduced diffusing capacity, lower exercise capacity, and impaired respiratory-muscle strength ,11. RiskCardiopulmonary rehabilitation is the basis for dealing with people suffering from chronic lung diseases. Its strategy is based on individualized rehabilitation programs, which include aerobic exercises, breathing exercises, and muscle-strengthening exercises. There is ample evidence supporting the benefits of pulmonary rehabilitation in terms of disease mortality, improved cardiorespiratory fitness, and quality of life ,14.Improved respiratory function is an important symptom of recovery from COVID-19. According to the recommendations of scientific societies, pulmonary rehabilitation programs should be implemented in patients after COVID-19 ,16,17,18The aim of this study is to evaluate the effect of inpatient rehabilitation, implemented according to the Polish National Health Fund guidelines, on lung function in COVID-19 patients. The effectiveness of rehabilitation was measured by the improvement in spirometric parameters. An additional objective is to determine the relationship between spirometric parameters before and after rehabilitation and gender, age, body mass index (BMI), length of hospitalization, and the presence of COVID-19-associated pneumonia.The study was conducted between May 2021 and September 2022 at the St. Charles Borromeo Rehabilitation Hospital in Szczecin (Poland), where inpatient rehabilitation of COVID-19 patients was carried out in accordance with the guidelines of the National Health Fund (NFZ), as indicated in Order No. 42/2021/DSOZ of the President of the NFZ dated 5 March 2021.The study included 171 patients qualified for inpatient rehabilitation following SARS-CoV-2 infection, each based on a referral issued by a physician no later than 12 months after the completion of treatment for COVID-19, confirmed by a positive polymeraze chain reaction (PCR) test for SARS-CoV-2. The completion of treatment was defined as the date of completion of home isolation, discharge from the hospital, or end of isolation.Patients’ eligibility criteria were post-COVID-19 respiratory or cardiovascular or nervous-system or musculoskeletal complications  Scale). Patients who experienced a decrease in muscle strength  muscle-strength score) or an increase in dyspnea  dyspnea score) were also eligible for rehabilitation. Only patients who gave informed consent were included in the study.The exclusion criteria for the study were age under 18 and lack of consent. Patients who performed the spirometric test incorrectly or could not perform it due to contraindications were excluded from the study. Taking into account all inclusion and exclusion criteria, 150 patients participated in the study .Patients actively participated in the post-COVID-19 rehabilitation program, according to the regimen of the St. Charles Borromeo Rehabilitation Hospital in Szczecin. Rehabilitation activities were carried out six times a week, from Monday to Saturday. Sunday was a day off. A detailed rehabilitation program is presented in The duration of rehabilitation, as recommended by the National Health Service, lasted 2 to 6 weeks. Throughout the rehabilitation period, each patient was under medical and nursing care. The length of the patient’s stay in the rehabilitation unit was decided by the attending physician, based on a comparison of the results of examinations and tests, such as the exercise test with exercise tolerance assessment and spirometric respiratory functional assessment, carried out at the beginning and end of treatment.Functional assessment of the lungs was determined by spirometry on the day of admission to the rehabilitation unit, on the day of discharge from the rehabilitation unit, and 2 months after completion of rehabilitation. The portable spirometer BTL-08 Spiro  was used for the measurement. The following parameters were determined: forced expiratory volume in the first second (FEV 1), forced vital capacity (FVC), FEV 1/FVC ratio, maximal expiratory flow (MEF) 25–75%, maximal mid-expiratory flow (MMEF), and peak expiratory flow (PEF). Results were expressed as a percentage of the patient’s predicted normal values, which were calculated automatically based on age, gender, height, weight, and ethnicity. The FEV1/FVC ratio is shown as an absolute value. For the interpretation of spirometry data, ECCS/ERS 1993 reference values were used. Normal values for these parameters are FVC > 80%, FEV1 > 75%, FEV1/FVC > 75%, MEF75, MEF50, and MEF25 > 75% of the reference value . All spiOn the day of admission to the rehabilitation department, an additional interview was conducted to obtain demographic data. Information regarding the patient’s medical history and treatment, as well as comorbidities, was obtained from medical records.The study was approved by the Bioethics Committee of Pomeranian Medical University in Szczecin (decision no. KB-0012/15/2021).t-test and the Mann–Whitney U-test. The difference between multiple groups was analyzed by the Kruskal–Wallis test or by the ANOVA test. Correlation analysis was performed using Spearman’s Rho test. Nominal variables were tested using the chi-squared test. Dependent variables were tested with the t-test for dependent samples and the Wilcoxon test. Multivariable logistic regression analysis was performed. For the logistic regression analysis, an increase in FVC after rehabilitation was assumed as a predictor of lung-function improvement. The model for multivariable logistic regression was adjusted for gender, age, body mass index, pneumonia, and length of hospitalization. A p-value of <0.05 was regarded as statistically significant.Statistical analysis was carried out using Statistica (version 13.1). Characterization of the study group was performed, taking into account the number of patients, patients’ percentage, mean, median, first and third quartiles, and standard deviation. Normality of distribution was tested using the Shapiro–Wilk test. For the normal distribution, the data are presented in the mean and standard deviation. For the non-normal distribution, the data are presented in the median, first, and third quartiles. The differences between two groups were analyzed using Student’s A total of 150 subjects were included in the study. They were characterized in terms of age, gender, and nutritional status. The need for hospitalization, length of hospitalization, presence of pneumonia in the course of SARS-CoV-2 infection, and length of stay in the rehabilitation unit after COVID-19 were also analyzed.The average age in the study group was 64.66 (±11.93) years. The average height and weight of the study population were 168.08 cm (±9.5) and 82.67 kg (±17.63), respectively. The average body mass index (BMI) was 29.16 (±5.68). The characteristics of the study population are shown in p = 0.016), FEV1 (p < 0.001), PEF (p < 0.001), MMEF (p < 0.001), MEF75 (p < 0.001), and MEF 50 (p < 0.001). Detailed results are shown in The analysis of the results is presented in the form of correlations between spirometric test parameters before and after rehabilitation. Improvement in spirometric parameters was observed for FVC (p = 0.026) and FEV1 (p = 0.007).p = 0.033).A post hoc analysis of statistically significant differences in parameters in the intergroup analysis of multiple variables  was performed. It was shown that there were no statistically significant differences between the analyzed groups.p = 0.012) and first-degree obesity .The results of the multivariate regression analysis are presented in Cardiopulmonary rehabilitation programs are recommended in the care of patients recovering from COVID-19 to prevent long-term complications in the musculoskeletal, respiratory, and circulatory systems. Individualized rehabilitation programs that include aerobic, muscle-strengthening, and respiratory exercises may allow a faster recovery of COVID-19 patients .The present study evaluated the short- and long-term effects of rehabilitation on spirometric parameters in COVID-19 patients. A multivariate analysis was also performed to assess the relationship between spirometric parameters before and after rehabilitation and gender, age, body mass index (BMI), length of hospitalization, and the presence of SARS-CoV-2 infection pneumonia.The present study showed a significant improvement in pulmonary function confirmed by spirometry after rehabilitation compared to the pre-rehabilitation evaluation. Similar results are presented by Hockele et al. , who useOur study was not randomized and did not include a control group for those with COVID-19 but without rehabilitation. Following the study of Liu et al. [A number of authors evaluated the lung function of COVID-19 patients at different times since recovery but without any rehabilitation ,28,29. ZTo the best of our knowledge, the present study is the first to evaluate the factors affecting the improvement in spirometric parameters in patients after COVID-19. Our study shows that people with overweight and the first-degree of obesity showed significantly less improvement in lung-function parameters after rehabilitation. Guler et al.  showed tA limitation of this study was the lack of a control group. However, for ethical reasons, this was not possible. Patients with asthma and COPD who may have already had pulmonary dysfunction were included in this study. However, after analyzing the results of the spirometry test, they showed no significant differences from the rest of the group. Another limitation of this study was the varying time between the onset of COVID-19 and the first day of rehabilitation. However, it was not longer than 12 months. The duration of the rehabilitation cycle was also not uniform—it ranged from 2 to 6 weeks. The indicated factors may affect the final results of this study.The strength of this study is the supervised rehabilitation process. All patients performed exercises in a stationary center under the constant supervision of physiotherapists. In future studies, it would be interesting to investigate respiratory function with additional tests, such as the plethysmography or lung gas diffusion capacity (DLCO) tests.A rehabilitation program based on aerobic, strength, and endurance exercises improved lung-function parameters in patients after their recovery from COVID-19. The achieved effects of rehabilitation were sustained in the long term. The improvement in spirometric parameters in patients after COVID-19 may be related to body mass index (BMI).


Although recent studies have shown that the human microbiome is involved in the pathogenesis of allergic diseases, the impact of microbiota on allergic rhinitis (AR) and non-allergic rhinitis (nAR) has not been elucidated. The aim of this study was to investigate the differences in the composition of the nasal flora in patients with AR and nAR and their role in the pathogenesis.From February to September 2022, 35 AR patients and 35 nAR patients admitted to Harbin Medical University’s Second Affiliated Hospital, as well as 20 healthy subjects who underwent physical examination during the same period, were subjected to 16SrDNA and metagenomic sequencing of nasal flora.The microbiota composition of the three groups of study subjects differs significantly. The relative abundance of Vibrio vulnificus and Acinetobacter baumanni in the nasal cavity of AR patients was significantly higher when compared to nAR patients, while the relative abundance of Lactobacillus murinus, Lactobacillus iners, Proteobacteria, Pseudomonadales, and Escherichia coli was lower. In addition, Lactobacillus murinus and Lacttobacillus kunkeei were also negatively correlated with IgE, while Lacttobacillus kunkeei was positively correlated with age. The relative distribution of Faecalibacterium was higher in moderate than in severe AR patients. According to KEGG functional enrichment annotation, ICMT is an AR microbiota-specific enzyme that plays a role, while glycan biosynthesis and metabolism are more active in AR microbiota. For AR, the model containing Parabacteroides goldstemii, Sutterella-SP-6FBBBBH3, Pseudoalteromonas luteoviolacea, Lachnospiraceae bacterium-615, and Bacteroides coprocola had the highest the area under the curve (AUC), which was 0.9733(95%CI:0.926-1.000) in the constructed random forest prediction model. The largest AUC for nAR is 0.984(95%CI:0.949−1.000) for the model containing Pseudomonas-SP-LTJR-52, Lachnospiraceae bacterium-615, Prevotella corporis, Anaerococcus vaginalis, and Roseburia inulinivorans.In conclusion, patients with AR and nAR had significantly different microbiota profiles compared to healthy controls. The results suggest that the nasal microbiota may play a key role in the pathogenesis and symptoms of AR and nAR, providing us with new ideas for the treatment of AR and nAR. There avia HDAC, thereby reducing allergic airway diseases  and registered with the China Clinical Trial Registration Center (registration number ChiCTR2200057919). All subjects and control groups have informed consent, and the case conforms to the ethical norms of the Helsinki Declaration .2.1.1The control group: (1) healthy people selected for the physical examination of the Second Affiliated Hospital of Harbin Medical University and the examination results are normal; (2) there is no history of allergies or family allergies; (3) There are no allergy-related symptoms; (4) After a comprehensive physical examination such as allergen testing, no factors that may cause deviation from the results of this test have been found; (5) Voluntary participation in this study.AR group: (1) Comply with the diagnostic criteria of AR in the Guidelines for the Diagnosis and Treatment of Allergic Rhinitis  , paroxysnAR group: (1) Have different degrees of clinical symptoms such as nasal congestion, runny nose, nasal itching, sneezing, etc.; (2) All SIgE test results are negative (<35kU/L); (3) All SPT test results are negative; (4) Total serum IgE negative (<100IU/mL); (5) Negative for nasal allergen provocation test (NAPT);(6) Participate in this study voluntarily.2.1.2The above subjects met the following exclusion criteria: (1) Patients on systemic or topical antibiotics, immune agents, glucocorticoids, and antihistamines within 3 months.; (2) Other related diseases in the nasal cavity: sinusitis, nasal polyps, benign and malignant tumors, nasal boils, carbuncles, intranasal infections, Nose bleeding within 1 month; (3) Other respiratory diseases: chronic obstructive pulmonary disease, asthma, bronchiectasis, tuberculosis, pneumonia, pulmonary heart disease, pulmonary malignant tumors; (4) Hypertension, coronary heart disease, hyperthyroidism, hypothyroidism, liver and kidney dysfunction, blood system diseases, etc.; 5) The patient has a history of mental and neurological diseases; (6) The abnormal examination results of clinical signs before the trial may deviate the results of this trial according to the judgment of the researchers; (7) Patients with nasal irrigation within 2 weeks.2.2Use the total score of nasal symptoms (TNSS) to evaluate the severity of the symptoms. TNSS score: 0 to 3 . Mild: no symptoms that cause obvious discomfort; Moderate: Symptoms cause discomfort but do not affect daily life or interfere with sleep; Severe: Symptoms interfere with daily activities and sleep status. Add the points of each symptom, and get a total score is TNSS . RQLQ is2.3Guide the swab to the lower turbinate area under the nasal endoscope, rotate at least six times until the swab is saturated, remove it, put it in a liquid nitrogen bottle, and refrigerate at -80°C for 15 minutes until DNA is extracted.2.42.4.1The genomic DNA of the sample is extracted by CTAB or SDS method, then use agarose gel electrophoresis to detect the purity and concentration of DNA, and use sterile water to dilute an appropriate amount of sample to 1ng/μL. Using diluted genomic DNA as a template, select the V3-V4 area and use specific primers with Barcode and high-efficiency high-fidelity enzymes for PCR. The PCR products that passed the test were purified by magnetic beads, quantified by enzyme labeling, and mixed with the same amount of samples according to the concentration of PCR products. After full mixing, use 2% agarose gel electrophoresis to detect the PCR products and construct the library. The constructed library was checked with Qubit and Q-PCR for quantification, and the qualified library will be sequenced.2.4.2® dsDNA Assay Kit in Qubit® 2.0 Fluorometer  to check DNA for quantification. Take an appropriate amount of sample into a centrifuge tube, and dilute the sample with sterile water until the OD value is between 1.8-2.0. Take 1μg genome DNA of the sample and use NEBNext® Ultra, DNA Library Prep Kit for Illumina  to construct the library. The genomic DNA was randomly sheared into fragments with a length of about 350 bp using Covaris ultrasonic crusher. The obtained fragments were end-repaired, A-tailed, and further ligated with a sequence adapter. The fragments with adapters were PCR amplified, size selected, and purified to construct the library. The constructed library was checked with Qubit2.0 for quantification, diluted to 2ng/ul, and then the insert size of the library was detected with Agilent 2100. After the insert size meets the expectation, the Q-PCR method is used to accurately quantify effective library concentration (effective library concentration is>3nM) to ensure the quality of the library. Quantified libraries will be pooled and sequenced on Illumina PE150 platforms, according to effective library concentration and data amount required.Use 1% agarose gel electrophoresis (AGE) to analyze the purity and integrity of DNA, and use Qubit2.52.5.1Use the Uparse algorithm to cluster sequences into OTUs and annotate species, use Qiime software to calculate Chao1, Shannon, Simpson and ace indexes, draw diluted curves and species accumulation curves, and analyze differences between Alpha diversity index groups. R software is used to analyze the differences between Beta diversity index groups, including LEfSe analysis, MetaStat analysis, and t.test_bar_plot analysis to compare the differences between groups, calculate the Spearman correlation coefficient values of species and environmental factors and test their significance. Based on species abundance, the correlation coefficient value between each genus is calculated using graphviz-2.38.0 to draw a network diagram, and MeanDecreeAccuracy chose a meaningful genus to build a random forest model.2.5.2Use MetaGeneMark for ORF prediction, and use Bowtie2 (Bowtie2.2.4) to compare the Clean Data of each sample to the initial gene catalog for basic information statistics, core-pan gene Analysis, correlation analysis between samples, and gene number Wayne diagram analysis. The sequence extracted from the NR database of NCBI is compared with Unigenes, the LCA algorithm is used to determine the species annotation information, Krona analysis is carried out, and then Metastats and LEfSe analysis are used to find different species between groups. Unigenes were compared with the KEGG database using DIAMOND software for annotated gene number statistics, relative abundance profile display, abundance clustering heat map display, comparative metabolic pathway analysis, and Metastat and LEfSe analysis of functional differences between groups based on abundance at each taxonomic level.33.1The mean age of the AR group was 21.03 ± 9.94, the TNSS score was 10.03 ± 3.67, the RQLQ score was 102.8 ± 29.64; the mean age of the nAR group was 33.73 ± 10.73, the TNSS score 8.77 ± 2.24, RQLQ score 89.67 ± 26.43, mean age of control group: 29.7 ± 12.25, AR group was significantly younger than the nAR group (p<0.001), and TNSS score and RQLQ score did not differ between the two groups (p>0.05) Table 1.3.23.2.1A total of 18,364 OTUs were obtained from the three groups by 16SrDNA assay, with 2515 OTUs specific to the AR group and 3512 OTUs specific to the nAR group, and a total of 8476 OTUs in the two groups. There were fewer specific OTU in the AR group than in the nAR group ; Corynebacterium propinquum and Prevotella buccalis were positively correlated with IgE, and Lactobacillus murinus and Lactobacillus kunkeei were negatively correlated with IgE  and severe (8-16) groups and compared bacterial diversity and community differences to explore the role of bacterial community structure in the progression of AR. Results show that diversity was not significantly different, and LEfSe analysis showed that the mean relative abundance of Faecalibacterium was higher in the moderate group than in the severe group, and the mean relative abundance of Ralstonia pickettii and Cupriavidus was lower than in the severe group, suggesting a role for specific flora in the progression of the disease Figure 53.2.6This is a classical machine learning model based on a classification tree algorithm that provides further support for differentiating AR groups, nAR groups, and control groups. Based on the analysis of OTU features, a random forest prediction model with 5 genera was constructed. Mean Decree Accuracy selected meaningful genera, performed 10-fold cross-validation of the model, plotted working characteristic (ROC) curves, and calculated the area under the curve (AUC) to score the predictive power.The results showed that mainly Parabacteroides goldstemii, Lachnospiraceae bacterium 615, Sutterella-SP-6FBBBH3, Pseudoalteromonas luteoviolacea, and Bacteroides coprocola were observed in the models of AR and healthy controls   . Galectiin (CBP) . GBP canin (CBP) . TherefoWe discovered that Lacttobacillus kunkeei was positively correlated with age using correlation analysis. In this study, the average age of onset in the AR group was 21.03 ± 9.94 years, while it was 33.73 ± 10.73 years in the nAR group. The relative abundance of Lacttobacillus kunkeei increased in the nAR group, implying that increased pathogenicity manifested by microbiota changes may be age-related. Previous studies have shown an association between Lactobacillus and age, with increased abundance with age  and thatPrevious research has shown that random forest analysis can predict the occurrence of AR . Our fin9 CFU) or cetirizine (2.5-5 mg) showed significant improvement in baseline AR symptoms in more than 95% of participants after 6 weeks of intervention (Currently, there is growing interest in the application of probiotics to modulate microecological balance in the treatment of AR, defined by the World Health Organization as living microorganisms that, when administered in adequate amounts, provide health benefits to the host. This beneficial effect was initially thought to stem from improved gut microbial balance, but there is now substantial evidence that probiotics can also provide benefits by modulating immune function . In animrvention . This va5In conclusion, this study establishes nasal microecological regulation as a potential therapeutic target for AR and nAR. We discovered that AR patients differed significantly from nAR patients and healthy controls in terms of nasal bacterial α and β diversity. AR is closely associated with an increase in the relative abundance of vibrio vulnificus and Acinetobacter baumanni, and an increase in the relative abundance of Lactobacillus iners, Lactobacillus murinus, and Escherichia coli may also be a key factor in the occurrence of nAR. The anti-inflammatory effect of probiotics such as Lacttobacillus kunkeei and Escherichia iners and the antagonism of ICMT could be a future treatment strategy for AR. Glycan biosynthesis and metabolism may play a role in the pathogenesis of AR, which will be investigated further in the following step. The joint detection of microbiota based on random forest results may also provide us with new ideas for future AR and nAR diagnosis.The data presented in the study are deposited in the NCBI repository, accession number PRJNA936719.The studies involving human participants were reviewed and approved by China Clinical Trial Registration Center, CHINA. The patients/participants provided their written informed consent to participate in this study.JW and YS conceived and designed the research. YC, NW, and QM conducted the experiments. JL and ZX analyzed the data. YC and QL wrote and edited the manuscript. All authors contributed to the article and approved the submitted version.