Telomere dynamics play a crucial role in the maintenance of chromosome integrity; changes in telomere length may thus contribute to the development of various diseases including cancer. Understanding the role of telomeric DNA in carcinogenesis and detecting the presence of cell-free telomeric DNA (cf-telDNA) in body fluids offer a potential biomarker for novel cancer screening and diagnostic strategies. Liquid biopsy is becoming increasingly popular due to its undeniable benefits over conventional invasive methods. However, the organization and function of cf-telDNA in the extracellular milieu are understudied. This paper provides a review based on 3,398,017 cancer patients, patients with other conditions, and control individuals with the aim to shed more light on the inconsistent nature of telomere lengthening/shortening in oncological contexts. To gain a better understanding of biological factors  affecting telomere homeostasis across different types of cancer, we summarize mechanisms responsible for telomere length maintenance. In conclusion, we compare tissue- and liquid biopsy-based approaches in cancer assessment and provide a brief outlook on the methodology used for telomere length evaluation, highlighting the advances of state-of-the-art approaches in the field. Telomeres have been studied for decades, as they are related to important biological processes such as aging and the development of various diseases. As they play a crucial role in maintaining chromosome integrity, its deregulation and telomere length (TL) changes may lead to various age-related disorders, cardiovascular disease, or cancer development. Recent findings suggest cell-free telomeric sequences in circulation may also play regulatory roles in fine-tuning of the immune system . DespiteLiquid biopsies involving the analysis of various biomolecules contained in the patient’s bodily fluids has become increasingly popular recently because of its undeniable benefits over conventional invasive methods . This apIn this paper, we summarize the mechanisms responsible for maintaining telomere length to better understand the biological factors affecting telomere homeostasis across different types of cancer cells. We focused on the studies looking into liquid biopsy-based telomere length analysis in cancer assessments. For early identification of telomere changes at a disease stage when the concentration of circulating tumor DNA is below the detection limit of standard methods, it is essential to apply highly sensitive methods. We therefore also provide a brief outlook on the methodology used for telomere length evaluation, highlighting the advances of state-of-the-art technologies in the field.Telomeres are protected by specialized nucleoprotein capping structures consisting of DNA and shelterin protein complexes . Human tp53 gene or other checkpoint proteins. As a result, they continue to proliferate, acquire immortality, and proceed to carcinogenesis [Telomere shortening can occur through two distinctive mechanisms . The firogenesis ,19.TERT expression regulated by transcription factors but it is also influenced by the epigenetic status [TERT expression correlates positively with the levels of methylation at the TERT promoter region. At the same time, it correlates negatively with the level of gene coding sequence methylation [To acquire replicative immortality, cancerous cells need to overcome the shortening of telomeres ,20. Mostc status ,27. As ohylation ,29. It whylation  as well hylation . We therAs telomeres shorten, they can also modify gene expression at the level of transcription by the telomere position effect (TPE) ,33. Due Although telomeres were considered to be transcriptionally silent, it has been recently shown that mammalian telomeres undergo transcription into telomeric repeat-containing RNA (TERRA) . This loTelomeres are protective DNA–protein structures at the end of chromosomes that prevent genome degradation and inappropriate activation of DNA responses . They caTelomeropathies are characterized by premature telomere shortening caused by mutations in genes involved in telomere maintenance or the DDR system. Based on the age of disease onset, severity, and type of organ systems affected, telomeropathies can be divided into three groups: (I) telomeropathies with very early onset and severe course ; (II) dyskeratosis congenita (DKC); and (III) cryptic telomeropathy, a form of DKC with a later onset . CurrentTelomere shortening has been associated with several disorders, including type 1 and type 2 diabetes , cardiovTERT and TERC gene amplification, TERT promoter (TERTp) mutation and methylation, genomic rearrangement of TERT , post-transcriptional regulation by microRNAs, and alternative splicing of the TERT gene [In cancerous cells, high telomerase activity overcomes the limitation of replication thus avoiding activation of the DNA damage signaling pathway . SeveralERT gene ,68.TERTp mutations are likely to be the most important mechanism participating in telomerase reactivation and TERT expression adjustment [TERTp is typically not covered by the whole-exome sequencing (WES) analysis, it is absent from most genomic studies. Said mutations may not only affect TERT expression but also telomere length and telomerase activity by way of abrogating telomerase silencing [TERT expression. The two most frequent TERTp mutations are C228T and C250T transitions found at -124 bp and -146 bp, respectively from the site of the transcription start [TERT expression which was initially observed in melanomas [TERTp were detected at different frequencies in cancers with high  and cer 0.9% , bladdercer 0.9% , and hepcer 0.9% ) prolifecer 0.9% . TERTp multuring , and itsulturing . In cancigenesis . Moreoveic event . TERTp mferation . An intr and IDH ,87,88.TERT locus have been associated with cancer risk [TERT-CLPTM1L 5p15.33 chromosomal region associated with susceptibility to 11 various cancers and 1 non-cancer disease (idiopathic pulmonary fibrosis).Several SNPs in the cer risk . The moscer risk  showed acer risk ,89. Morecer risk  found 13On the other hand, ALT is frequently observed ,29 in a Regulation of telomerase expression, assembly, and function occur across all levels of gene expression and is governed by a range of intracellular and environmental stimuli that share substantial overlap with pathways that control malignant transformation and tumor progression . Thus, tLiquid biopsies have shown tremendous potential in detecting early-stage cancers, selection of targeted therapies, monitoring disease progression, or post-surgical detection of residual disease . This isThe presence of cfDNA in circulation is not exclusive to cancer, but the levels in cancer patients are increased due to its additional release by tumor cells, known as circulating tumor DNA (ctDNA) . A smallSingle liquid biopsy biomarkers often cannot deliver accurate prediction of the disease state due to heterogenous phenotype and disease expression across individual patients. To deal with this challenge, researchers combine multiplexed measurements spanning across a full range of various biomarkers that combine to define robust signatures for different disease states. Machine learning may be regarded as a helpful instrument delivering automated discovery and detection of said signatures, especially as new technology leads to increasing quantities of molecular data output .The measurement of the leukocyte telomere length (LTL) from peripheral blood represents the gold standard for evaluating the dynamics of TL changes. It is usually provided by way of qPCR   compared to hematopoietic stem cells . To achiThe advantage of measuring LTL is the simplicity and availability of blood sampling that can be performed by a nurse in an outpatient setting, while measuring TL from a tissue biopsy requires a team of health workers cooperating during invasive sample collection and presents certain health risks for the patient. However, it is necessary to thoroughly understand the correlation between LTL and TL in tumor tissues in the respective types of cancer in order to use LTL as a biomarker for monitoring the dynamics of cancer development and treatment.Over the past decade, much effort has been devoted to the development of non-invasive approaches for cancer diagnosis and monitoring to replace the conventional invasive techniques ,130,131.Wu and Tanaka quantified plasma cf-telDNA levels in breast cancer patients . They foTERT mRNA may be detected in the plasma of cancer patients. Moreover, the measured levels significantly correlate with those in tumor samples [TERT mRNA is not detected in the plasma sampled from healthy individuals [TERT mRNA is an independent prognostic marker for various tumor types [TERT mRNA as opposed to individuals from the non-tumor cohort both not only at baseline but also in follow-up samples. These findings are in line with the evidence that an increased TERT expression represents a hallmark of cancer [TERT is a key rate-limiting catalytic subunit with low or absent expression in normal cells. However, it plays a key role in sustaining the unlimited replication potential of cancerous cells , suggest samples . Furtherividuals ,146. In or types , includior types , prostator types , lung [1or types , and color types ,151,152.or types . Cangemior types  found thf cancer .Because of the importance of telomeres in human physiology, various methods have been developed to measure telomere length ,156. SevCastle et al.  providedThe PubMed search for the term “telomere length” AND “cancer” has shown a gradual decrease in the number of publications from 2017 onwards, suggesting that scientists have depleted the potential of conventional approaches to studying telomere length in cancer . Thus, uLong-read sequencing enables the sequencing of DNA longer than 10 kilobase pairs, representing an emerging approach suited for the study of long repetitive elements like telomeres . Indeed,To our knowledge, there is no accepted consensus on whether telomeres are lengthened or shortened in cancer. The literature indicates that there are telomere length differences between diseases, cells/tissues, types of biological material, and methods used for telomere analysis. Since the current knowledge is based on various methodologies, understanding the strategies for telomere length measurements is necessary to compare the results published in different studies. Despite the increasing amount of next-generation sequencing data entering the clinical routine, analyses of telomere length by short-read MPS have not yet been widely implemented in practice. Another factor coming into play is the bioinformatics tools enabling telomere detection or telomere length measurements that have reached a high level of applicability to estimate telomere length from MPS data. Telomere length testing has the potential to provide assistance to physicians when identifying patients who are at risk of developing telomere-related disorders and their associated complications. However, the bilateral nature of telomere length changes in cancer remains a challenge to be addressed. It will therefore be necessary to explore other biological factors that could explain this phenomenon. The current methodology seems to be sufficient, but large-scale validation studies will be necessary to confirm cf-telDNA length as a reliable biomarker for biomedical applications in cancer screening, early diagnosis, or monitoring.


Purtscher-like retinopathy (PLR) is an uncommon occlusive microangiopathy associated with various systemic conditions. We report a case of PLR related to severe progressive systemic sclerosis (SSc), an autoimmune disease characterized by widespread angiopathy and fibrosis, in a 44-year-old Caucasian male diagnosed with early diffuse cutaneous systemic sclerosis (dSSc). Upon ophthalmological examination, pathognomonic fundoscopy abnormalities were found. Spectral domain optical coherence tomography (SD-OCT), angio-OCT, and visual field results are documented at initial diagnosis and follow-up visits. The detailed ophthalmological assessment is juxtaposed with rheumatological evaluation and treatment. Current literature on probable pathophysiological mechanisms is reviewed in accordance with the described case. The PLR seems to be connected to severe SSc-related angiopathy initiated by capillary endothelial damage, with ultimate arteriolar precapillary occlusion in the inner retinal layer. Although this is not routinely recommended, we suggest that ophthalmological examinations may be advantageous in patients with SSc, as serious eye pathology may be present despite the lack of symptoms reported by the patient. Patients with PLR require a differential diagnosis and regular follow-up. Proper treatment of the underlying disease may have beneficial effects on the natural course of PLR. Purtscher-like retinopathy (PLR) is an uncommon occlusive microangiopathy associated with various systemic conditions. The most common causes are acute pancreatitis, renal failure, and autoimmune diseases, including systemic lupus erythematosus (SLE) and dermatomyositis ,2,3,4. TA 44-year-old Caucasian male diagnosed with early diffuse cutaneous systemic sclerosis (dSSc) (anti-Scl-70 antibodies positive (+++)) with a duration of 3 months was admitted to the Department of Rheumatology, Medical University of Bialystok, Poland, due to progressive skin thickening, painful ulcers on both hands , and sigThe patient had no previous history of severe trauma or ocular disease, and he denied any visual disturbance. Upon routine ophthalmological examination, the patient presented full uncorrected visual acuity (VA) bilaterally. The intraocular pressure (IOP) in the right eye (RE) and left eye (LE) was 17 and 16 mmHg, respectively. Slit-lamp examination revealed lid stiffness and telangiectasia on the upper and lower lids of both eyes, without any abnormalities in the anterior segment. Fundoscopy revealed cotton-wool spots confined to the posterior pole surrounding the optic disc and subtle Purtscher flecken, discrete areas of retinal whitening between the arterioles and venules (pathognomonic sign), in both eyes A.Spectral-domain optical coherence tomography  of both eyes showed hyperreflectivity in the nerve fiber layer, corresponding to cotton-wool spots and slight cystoid spaces in the macula of the RE . OCT thiFluorescein angiography of both eyes revealed vascular wall enhancement, vein dilatation, and capillary occlusion corresponding to the cotton-wool spots, as well as slight leakage within the macula and optic disc in the RE . OCT angA visual field test using a Humphrey visual field analyzer  with the 30-2 SITA Standard algorithm revealed arcuate scotoma in the RE and diffuse double arcuate scotoma in the LE A. A 120-Over a period of almost 12 months, the patient received nine infusions of tocilizumab, and methotrexate treatment was intensified (20 mg per week). Laboratory tests showed normalization of the troponin and NT-proBNP concentrations, with a tendency to decrease compared to previous hospitalizations .Purtscher’s retinopathy (PUR) occurs primarily as a result of cranial trauma or thoracic compression. However, in cases of nontraumatic etiology, the correct term is Purtscher-like retinopathy (PLR) . The mosThe pathogenesis of PUR/PLR remains unclear, and several mechanisms have been proposed to date. Arteriolar precapillary occlusion resulting in an infarct of the retinal nerve fiber layer appears to be the most accepted and consistent possibility. Fat emboli, pancreatic protease in systemic circulation, or leukocyte aggregation and C5 complement activation can lead to microembolization. Other, rarely proposed pathogenic processes include vascular endothelial dysregulation and capillary endothelial damage followed by endothelin-induced vasculopathy . HarrisoChoroidal vessel involvement in PUR/PRL has also been discussed. In one study, indocyanine green angiography revealed areas of choroidal hypofluorescence, and the authors suggested that the involvement of the choroidal vasculature may occur more often than expected and may be associated with a worse prognosis for vision improvement . HistopaThe most frequently reported ocular manifestation of SSc is keratoconjunctivitis sicca, but skin changes of the eyelids (such as lid stiffness and tightness) are the most consistent features related to the underlying disease in patients with SSc . Kreps eIt is worth noting that among autoimmune diseases, PLR is most frequently described as coexisting with SLE; however, SLE is more common than SSc. It has been reported that PLR is a devastating and severe complication of SLE, and an association of PLR with central nervous system involvement in lupus and highly active disease has been observed. It has been hypothesized that endothelial damage related to vasculitis could play a key role in the pathogenesis of PLR in patients with SLE .Most cases of PLR are bilateral, with variability in visual disturbances (asymptomatic full VA to light perception) . The mosRegular follow-up of patients with PLR is worth consideration. Harrison et al. suggested examination by an ophthalmologist with funduscopic evaluation at least 1 month, 2 months, and 6 months after initial diagnosis. Although normalization of the retinal appearance has been observed in 40% of patients, optic nerve atrophy, mottling of the retinal pigment epithelium, retinal thinning, and narrowing of the retinal arteries can occur . RecurreOur case report has some strengths, including a relatively long follow-up period and detailed imaging results change during this period. The study has some potential limitation. As our patient did not report any visual disturbances , we do not know at what stage of the disease the PLR diagnosis was made. It is possible that fundus changes might have been more advanced. Due to the rarity of the disease this is a case report and not a case series.At present, there are no clear treatment recommendations for PLR due to the rarity, varied etiology, and heterogenous course of this condition. Further studies are needed to determine whether treatment could change the natural course of the condition. The effectiveness of corticosteroid treatment has not been proven . Proper In our patient, PLR seemed to be connected to severe SSc-related angiopathy initiated by capillary endothelial damage, with ultimate arteriolar precapillary occlusion in the inner retinal layer.Our case shows that although it is not routinely recommended, ophthalmological examination may be advantageous for patients with SSc, as serious eye pathology may be present despite a lack of symptoms reported by the patient. Patients with PLR require a differential diagnosis and regular follow-up. Proper treatment of the underlying disease can have a beneficial effect on the natural course of PLR.


Durvalumab is an immune checkpoint inhibitor (ICI) belonging to the anti-programmed death-ligand 1 (PD-L1) class, and it is used in the treatment of various end-stage malignancies. Immune checkpoint inhibitors are associated with various systemic and cutaneous adverse events. Psoriasiform drug eruptions have been clinically observed in patients who have a personal history of psoriasis being treated with ICIs. We present a unique case of de novo psoriasis in a patient being treated for poorly differentiated adenocarcinoma of the lung. The patient responded well to topical treatment and did not require discontinuation of durvalumab. Our case highlights the importance of clinician familiarity with psoriasis presentation, its association with durvalumab therapy, and treatment options for durvalumab-induced psoriasis. Immune checkpoint inhibitors (ICIs) are novel agents used for the treatment of various malignancies. These drugs include anti-programmed death 1 (PD-1) and anti-programmed death-ligand 1 (PD-L1), which inhibit the programmed cell death protein 1 and the programmed cell death ligand, respectively . Though A 74-year-old man with stage III poorly differentiated adenocarcinoma of the lung being treated with durvalumab after chemotherapy and radiation presented to our dermatology clinic. The patient had a personal history of atopic dermatitis during childhood; however, he denied having any personal or family history of psoriasis or any other autoimmune or rheumatologic disease. He had no significant comorbidities. A medication review showed no psoriasis-inducing drugs. After eight months of treatment with durvalumab, he developed multiple enlarging plaques on his left lower extremity and back. The patient described the lesions as mildly itchy and stated that the lesions were slowly enlarging. Clinical examination revealed three brown hyperkeratotic plaques on his left lateral lower leg and one plaque on the mid-lower back Figure .Given their unusual appearance and size, a shave biopsy of the largest lesion on the patient’s left lower leg was performed to confirm the diagnosis. The skin biopsy of the lesion revealed psoriasiform acanthosis with parakeratosis and the presence of Munro microabscesses, which was consistent with psoriasis Figure .Clinically, the patient’s presentation was consistent with rupioid psoriasis. Given that the patient’s psoriasis presented after the initiation of durvalumab, it is presumed that the patient developed psoriasis induced by durvalumab. Another possible differential diagnosis is seborrheic keratosis, which presents with waxy or scaly stuck-on plaque. This clinical presentation is similar to that of our patient; however, histopathology of seborrheic keratosis would reveal keratin-filled invaginations and small horn cysts. The patient’s psoriasis was limited to only a few lesions on the body, therefore, he was treated with clobetasol ointment to apply to the plaques twice a day. The patient’s oncologist continued his durvalumab for another four months, completing one year of therapy for the treatment of his lung adenocarcinoma. At the patient’s follow-up after durvalumab completion, his lesions had decreased in size, and he did not report any new plaques.Durvalumab is currently used for the treatment of a variety of malignancies, including metastatic non-small cell lung cancer, locally advanced or metastatic urothelial carcinoma, extensive-stage small-cell lung cancer, and metastatic Merkel cell carcinoma ,6. The rExisting literature supports the need for strict skin surveillance for patients on ICIs, such as durvalumab, who have a personal or family history of psoriasis . HoweverThis case is unique in that previously reported ICIs-induced drug eruptions often present as guttate or plaque psoriasis, whereas rupioid psoriasis, characterized by a hyperkeratotic cone-shaped plaque, has not been reported. While our patient did not have a personal history of psoriasis, he did report having a different inflammatory skin condition, atopic dermatitis, in childhood. Current literature supports the idea that patients with a history of autoimmune or inflammatory disease are significantly susceptible to immune-mediated adverse events when treated with ICIs .Psoriasis flares occurring during ICI therapy typically do not warrant immunotherapy discontinuation due to the severity of the underlying malignant conditions being treated with ICIs , 8. CurrImmune checkpoint inhibitors have shown remarkable efficacy in treating various cancers, but they can also induce rare side effects, such as exacerbating or even causing psoriasis, in patients with no prior history of this skin condition. When confronted with psoriasis flares during ICI therapy, healthcare providers often recommend a combination of treatment approaches. In mild cases, management can involve the use of oral antihistamines to alleviate itching, topical emollients to maintain skin hydration, and mild-potency topical corticosteroids to reduce inflammation. Importantly, the continuation of ICI therapy is typically advised to ensure that the patient receives the full benefit of cancer treatment while managing psoriasis symptoms. In more severe cases, biologics, immunosuppressive medications, or phototherapy may be necessary to control the psoriasis flare, always with a careful balance between treating the skin condition and maintaining the efficacy of the immune checkpoint inhibitors in fighting cancer.


During the COVID-19 pandemic in Germany, vaccination uptake exhibited considerable regional disparities. To assess the factors contributing to this variation, we examined the association of sociodemographic variables with COVID-19, COVID-19 booster, and influenza vaccination status within a cohort of 37,078 participants from 13 German federal states in the digital health cohort study commonly known as DigiHero. Our findings revealed variations in vaccination rates based on sociodemographic factors. However, these factors had limited explanatory power regarding regional differences in vaccine uptake. In contrast, we found substantial correlations between regional support of specific parties during the last local elections and the vaccination uptake at the level of each administrative district. In conclusion, sociodemographic factors alone did not suffice to explain the regional disparities in vaccine uptake. Political stances can play a major role, although the current investigation did not assess individual political orientations but rather used only an ecological approach. Vaccination against SARS-CoV-2 became available in the European Union at the end of 2020. In the summer of 2021, most of the German population had received basic immunization. Subsequently, the first booster vaccination became available towards the end of 2021. The spread of the Omicron variant was observed in numerous countries across the globe, including Germany, where the Robert Koch Institute (RKI)—the federal governmental agency in Germany tasked with the control and prevention of diseases—documented 16,748 Omicron cases as of 30 December 2021 [The introduction of available vaccinations against COVID-19 in 2021 met with strong resistance from some parts of the German population . VaccineIn Germany, there are notable disparities between former Eastern and Western federal states with respect to vaccinations. Vaccine hesitancy towards COVID-19 vaccines had a particularly noticeable presence in the former Eastern German states . EasternDue to respective recommendations from the STIKO (Standing Committee on Vaccination), a higher proportion of those aged 60 and above receive influenza or pneumococci vaccinations . During The outcome of vaccination uptake can be driven by both risk-benefit assessment and vaccine hesitancy. We hypothesized that regional differences in vaccination uptake are rather an indicator of vaccine hesitancy, while differences across age groups are rather an example of risk-benefit considerations. For other individual factors, like education, the distinction between both of these categories is less clear. Furthermore, theoretically, even knowledge of regionally different behavior can affect risk-benefit estimates, so hesitancy and risk-benefit considerations remain intertwined, and regional differences are only an indirect indicator of hesitancy. Given this contextual background, our objective was to investigate how much of the regional differences across federal states or within regions in Germany could be explained by differences in sociodemographic factors for COVID-19, COVID-19 booster, and influenza vaccinations. Furthermore, we studied whether regional differences in vaccine uptake were associated with support for specific political parties at the regional level. The data used in this study were collected in the population-based prospective cohort study for digital health research in Germany  . DigiHerIn the spring of 2023, we invited 70,538 participants from 13 federal states in Germany who had been recruited until then to answer questions regarding vaccinations against COVID-19 and influenza in the preceding autumn/winter season. Additionally, we collected information on all vaccinations against SARS-CoV-2 since the beginning of the pandemic. In our study, individuals who have received four doses or more are considered to have received a SARS-CoV-2 booster vaccination. We combined these data with sociodemographic information from the initial questionnaire. We categorized education levels based on the International Standard Classification of Education (ISCED-97) into three categories: low, medium, and high . In the We then retrieved results from the state elections in Saxony in 2019 and Saxony-Anhalt in 2021 at the administrative district (Landkreis) level from official election sources ,19. Descriptive statistics for this study are presented using frequencies and percentages. We employed generalized additive models (GAM) to effectively model vaccination uptake by age. We examined three outcomes: (i) receiving any vaccinations against SARS-CoV-2 versus none; (ii) receiving any booster vaccinations against SARS-CoV-2 versus none; and (iii) receiving an influenza vaccination in autumn/winter 2022/23 versus not receiving one. We examined the vaccination uptake across federal states initially without adjustments and subsequently accounting for sociodemographic factors such as age, sex, place of residence, urban/rural place of living, migration background, net household equivalent income, and education by a stepwise approach. We used the order of importance of the adjustment factors determined for any vaccination for the other outcomes as well. For the ecological analysis, we examined the regional variations in vaccination uptake within the federal states of Saxony and Saxony-Anhalt, both of which had participants from all administrative district units (Landkreis) in the DigiHero study. We then correlated these variations with the percentage of support for political parties.n = 1749), resulting in a final sample of 37,078. Those who responded to this questionnaire showed some differences in terms of sociodemographic data compared to those who did not participate, mainly a lower response rate among males, individuals in the youngest age group, and participants with low education and low income  completed the vaccination questionnaire between March and April 2023. We removed participants with incomplete vaccination data  assessment of the benefits and risks of being vaccinated against COVID-19; (ii) influence of existing social and political conditions; (iii) emotional responses to the pandemic and its social and political impact; and (iv) trust and confidence in health authorities and the vaccines themselves . RecurreSeveral other vaccines, apart from the SARS-CoV-2 vaccine, have faced resistance from the public. For example, the Hepatitis B vaccine and the HPV (Human Papillomavirus) vaccine are two modern vaccines that have encountered substantial resistance from the public . Many ofHesitancy towards the influenza vaccine was prominent even before the COVID-19 pandemic, and this hesitancy persisted when the initial COVID-19 vaccination rollout began in 2021. Less than half of the study participants were vaccinated for influenza, with the highest uptake observed in Eastern German states. This trend is consistent with previous research on influenza vaccination, which has shown higher coverage rates in Eastern Germany compared to Western Germany . VaccineThe low uptake of SARS-CoV-2 booster vaccination in the autumn/winter of 2022/23 suggests that a significant portion of the German population will have received their last vaccination more than 12 months ago by the autumn/winter of 2023/24. This is concerning because, during the winter season of 2022/23, a significant number of people continued to become infected with SARS-CoV-2 . While fOur study had several limitations. Firstly, our data included only information on vaccination uptake, so we did not assess vaccine hesitancy. Therefore, we can only indirectly infer concerning vaccination hesitancy from regional variation, after controlling for regional variation in sociodemographic factors. Furthermore, at the individual level, vaccine hesitancy can be intertwined with an individual risk-benefit assessment. An even more complex issue results from transmissibility of infections and the risk-benefit assessment can include considerations beyond one’s own health. Furthermore, at a more technical level, we considered only the number of vaccinations for COVID-19, while particularly in the early stages of the pandemic, infections were considered to provide protection for a certain period. This approach might have led to an underestimation of willingness for vaccination. Conversely, it is possible that those who participated in this study had a more positive attitude towards vaccination, which could have resulted in higher uptake estimates in our data. In fact, when we compared our findings to national data, we found a higher vaccination uptake, suggesting that our study participants may not fully represent the general population. Additionally, relying on study participants who may be more similar to each other across federal states than the general population of these states could have led to an underestimation of differences across federal states. Moreover, our questionnaire exclusively examined sociodemographic characteristics and did not explore political viewpoints or reasons for vaccine hesitancy. In our analysis, we compared vaccination proportions among study participants with external voting data. It is important to note that this approach may be susceptible to ecological fallacy. This was a simple correlation intended to provide an overall perspective rather than draw specific conclusions about the individual study participants’ political preferences. When correlating individual data with the percentage of support for political parties in state elections, we cannot infer the political preferences of individual participants. On the positive side, our study included a large sample size and provided regional-level data. We systematically recruited participants using a population-based approach, which differs from typical web-based studies.In summary, our analysis indicates that regional differences in the uptake of the studied vaccinations in Germany cannot be attributed to differences in sociodemographic factors alone. Instead, we observed different regional patterns after adjustment for sociodemographic data, and in the two federal states for which we had comprehensive regional coverage data. We also observed correlations between support of political parties and regional vaccination uptake. It appears that political stances and individual choices are rather intertwined, but this study used only ecological analysis for the assessment of this relation and could not infer individual participants’ political preferences.


Physical activity (PA) is known to have beneficial effects on health, primarily through its antioxidative stress properties. However, the specific metabolic pathways that underlie these effects are not fully understood. This study aimed to investigate the metabolic pathways that are involved in the protective effects of moderate PA in non-obese and healthy individuals. Data on 305 young, non-obese participants were obtained from the Qatar Biobank. The participants were classified as active or sedentary based on their self-reported PA levels. Plasma metabolomics data were collected and analyzed to identify differences in metabolic pathways between the two groups. The results showed that active participants had increased activation of antioxidative, stress-related pathways, including lysoplasmalogen, plasmalogen, phosphatidylcholine, vitamin A, and glutathione. Additionally, there were significant associations between glutathione metabolites and certain clinical traits, including bilirubin, uric acid, hemoglobin, and iron. This study provides new insights into the metabolic pathways that are involved in the protective effects of moderate PA in non-obese and healthy individuals. The findings may have implications for the development of new therapeutic strategies that target these pathways. This can explain the exercise-induced increase in 2-hydroxybutyrate, since a highly accelerated glycolytic flux during high-intensity exercise would result in a high rate of NAD+-to-NADH conversion at the level of glyceraldehyde 3-phosphate dehydrogenase /[NADrogenase . Our resrogenase .In the present study, glutathione metabolites  were associated with higher hemoglobin and hematocrit concentrations in males and females. Recent studies have suggested that a strong effect of oxidative stress (reduced glutathione) on glutathione peroxidase and glutathione reductase levels may reduce hemoglobin concentration in diabetic patients . This in2⋅− may underlie a prominent physiologic role despite being significantly less abundant than other endogenous and exogenous antioxidants [Our data also revealed that glutathione metabolites, including Cys-gly, oxidized, cysteinylglycine, and cysteinylglycine disulfide, were positively associated with liver function enzymes, including total bilirubin in both genders. Bilirubin can also act as an antioxidant in vitro, but whether its redox activity is physiologically relevant is unclear. Bilirubin’s unique redox activity toward Ooxidants . In addioxidants ,48.Our data also revealed a positive correlation between uric acid and glutathione metabolites in females. Reduced GSH and uric acid are of particular interest as they are both antioxidants that are closely linked to the energy metabolism homeostasis. The magnitude of increase in plasma uric acid level following a session of intense exercise was previously suggested to be differently affected by the type of exercise performed . AdditioOur findings are limited by the relatively small sample size and lack of assessment of the physiological mechanisms that are activated by the generation of free radicals during moderate-intensity physical exercise. Future studies will replicate these findings in larger cohorts and will assess the correlation between the identified biomarkers and the previously reported physiological mechanisms that are triggered by free radicals during exercise. Another limitation of our study is the presence of significant differences in multiple related clinical outcomes, such as lipid profile, between moderately active and inactive individuals. While these differences are integral to metabolic processes, considering them as potential confounders might affect the interpretation of our results. It should be noted that while our primary focus is on the correlation analysis across different exercise levels, there is potential value in considering the relationship between oxidative stress markers and clinical traits among sedentary individuals. Such an exploration could provide additional insights into the intricate interplay between oxidative stress and clinical characteristics, which will be considered in future studies.This study has shed light on the metabolic pathways underlying the protective effect of moderate exercise in non-obese, apparently healthy individuals, including lysoplasmalogen, plasmalogen, PC, vitamin A, glutathione and related metabolites, and xanthine metabolism. The identification of these metabolites and metabolic pathways in response to moderate physical activity provides a better understanding of exercise physiology as a potent antioxidant mechanism with therapeutic potential. The emerging data offer valuable insights for researchers investigating the long-term effects of regular exercise on the metabolism of healthy, active adults. This is especially significant given that the majority of previous research has focused on short-term responses primarily observed in athletes.


Intranasal administration offers a feasible, non-invasive method of delivering therapeutic drugs to the brain, allowing therapeutic pharmaceuticals to be administered directly to the central nervous system by bypassing the blood-brain barrier. Furthermore, exosomes are naturally occurring cell-derived nanovesicles that can serve as carriers for a variety of chemical compounds. Many studies have focused on artificial exosomes as innovative medication delivery methods. As a result, trans-nasal delivery of artificial exosomes might be employed to treat brain illnesses in a novel method. This review will outline the drug delivery mechanism of artificial extracellular vesicles, emphasize its advantages as a nasal drug carrier, particularly its application as a novel nanocarriers in brain diseases, and focus on its prospective application in chronic inflammatory nose disorders. Finally, artificial exosomes may become a unique drug delivery mode for clinical therapeutic usage. The blood-brain barrier (BBB) may be seen at the level of the cerebral microvasculature and is critical for maintaining homeostasis of the central nervous system (CNS) . The BBBEVs are naturally occurring cell-derived nanovesicles that convey information between tissue microenvironments. They also have the ability to alter target cell activity and differentiation . EVs areIn recent years, a variety of artificial exosomes that can overcome the shortcomings of natural exosomes have been developed. It has been reported to be effective in the treatment of cancer , ischemicur (curcumin-loaded in MESC derived exosomes) has greater stability and solubility and MESC-exoscur therapy dramatically reduced neurological scores, cerebral edema, and infarct volume  has been identified as a critical element involved in the pathophysiological process of IR injury . Recombiin situ administration of hydrogel embedded with miltefosine  and temozolomide -loaded targeted nanovesicles could suppress the tumor relapses. Because transferrin receptors are overexpressed on the surface of the tumor, surface engineering of vesicles can increase cellular uptake and medication internalization into tumor (Glioblastoma multiforme (GBM) is the most malignant primary tumor of the central nervous system, having a poor prognosis and a high mortality rate. Chemotherapy remains the primary therapeutic choice for GBM treatment and the existence of the BBB inhibits medication effects. to tumor . As a reto tumor   protein is constitutively active in several forms of human malignancies and is essential for tumor development, including GBM. Cucurbitacin I (JSI-124), as a potent STAT3 signaling pathway inhibitor, have antitumor properties in human breast cancer, neuroblastoma, lung cancer, murine melanoma cell lines and B cell leukemia . Furthere arrest . Therefoe arrest . On the e arrest .In a recent work, researchers used a pressure-based disruption and reconstitution procedure to load miRNA (anti-miRNA 21 and miRNA 100) while managing the size of microfluidically processed EVs (mpEVs) . In thisIt is evident that microglial cells, or brain-resident macrophages, play an important role in many CNS inflammation-related disorders, including meningitis, migraine headaches, Parkinson’s disease, and others. Curcumin, as previously said, not only has anticancer and preventative effects, but it is also a potent anti-inflammatory agent. After incubation, the mixture was centrifuged using a sucrose gradient to extract exosomal curcumin (Exo-cur), the size and morphology of Exo-cur were similar to those of natural exosomes . LPS-chaSpinal cord injury (SCI) is a crippling disorder with few treatment options and erratic recovery. The inherent obstacle to axonal development in the pathological phase of SCI is mostly phosphatase and tensin homolog (PTEN). PTEN downregulates cytoplasmic mammalian target of rapamycin (mTOR) activity and plays an important role in regulating the regeneration of corticospinal neurons . MSC-ExoA nasal nanovesicle delivery system (NVS) for pain treatment was created and developed in a recent study. Ketoprofen (KET), butorphanol (BUT), or tramadol (TRA) were incorporated in a phospholipid nanovesicular carrier in an animal model of pain, resulting in a faster onset and improved analgesic effectiveness . Accordiin vivo and in vitro induced a 2-fold increase in NMDEs secretion (Chronic rhinosinusitis (CRS) is a common clinical inflammatory disease of the nasal cavity and sinuses that often involves multiple sinuses . The patecretion . P-glycoecretion   is one of the most common upper respiratory disorders worldwide, with a convoluted cause. It is a nasal mucosal inflammatory condition induced by allergen exposure. The imbalance between Th1 and Th2 differentiation is implicated in the development of AR . Recent AR model . GAS5, aAR model . And EVsAR model   via trigeminal and olfactory nerves via axonal or endocytic routes and intra- or extra-neuronal pathways, respectively . Althougin situ chitosan hydrogels, mucoadhesive nanostructured lipid carriers, and chitosan nanoparticles, have been used to overcome the nasal mucosa barrier and improve the efficacy of drug therapy. However, several of these techniques may cause nasal toxicity and membrane component leaching, resulting in local irritation of the nasal mucosa. Full artificial EVs based on phospholipids have been developed for nasal delivery. This carrier has demonstrated the potential to improve drug delivery to the brain and the systemic circulation without generating nasal mucosal irritation or toxicity. Furthermore, the carrier combining magnesium ions with soft phospholipid vesicles and a mucoadhesive molecule called the phospholipid magnetosome was performed to explore a transport carrier with higher efficiency (Many artificial approaches, such as ficiency . This chAlthough several studies demonstrated that nasal administration of artificial nanovesicles had significant advantages in safety and transport efficiency on the treatment of brain illness. Collectively, the BBB is considered to be the main barrier to drug penetration into the CNS. Intranasal administration is an attractive alternative route to central nervous system administration because it bypasses the BBB more effectively than systemic administration. Artificial EVs can effectively cross the BBB. Intranasal administration of artificial EVs may be particularly appropriate for drugs that cannot achieve perfect blood concentrations in the brain due to the presence of the BBB, drugs that tend to cause adverse effects in peripheral tissues or in the blood, and drugs that are easily degraded by intravenous or oral administration. Although intranasal treatment has been shown to be effective in many brain illnesses, it has not been used in chronic inflammatory nose disorders. Only few reports on the use of artificial EVs in the treatment of chronic nasal diseases, such as chronic rhinosinusitis and allergic rhinitis. The great ability of artificial EVs in nasal disorders of the nasal cavity can be further explored in the future.


Increased cardiovascular (CV) morbidity and death are linked to obstructive sleep apnoea (OSA). The primary method of treating OSA is continuous positive airway pressure (CPAP). CPAP has some debatable outcomes on CV events in people suffering from OSA. The current study investigates how CPAP affects CV outcomes. The goal is to evaluate CPAP's effectiveness in lowering CV outcomes in OSA patients. We used a computer to search the PubMed, PubMed Central Library, Science Direct, and Google Scholar databases for studies comparing the effects of CPAP and a control group on CV outcomes in OSA patients. These included randomised control trials (RCT), narrative reviews, systematic reviews, case-control studies, observational studies and meta-analyses. A total of 52,937 patients were included in the final analysis of six RCTs, four observational studies, 10 meta-analyses, one case-control study, two systematic reviews and one narrative review. The weighted mean follow-up lasted for a period of between three months and nine years. The risk of major cardiovascular adverse events (MACE) was the same for both the CPAP and control groups. According to subgroup analysis, patients with lower MACE adherence rates (four hours per night) were more likely to use CPAP. The risk of all-cause mortality, CV-related complications causing mortality, acute myocardial infarction acute stroke, or hospitalisations for angina was the same in the CPAP and control groups. The primary outcome was that in patients with therapy with CPAP in addition to usual care and usual care alone did not prevent CV events in patients with moderate-to-severe OSA and existing CV illness. Patients with OSA who utilise CPAP may not experience fewer CV events. Patients who use CPAP consistently (four hours per night) could benefit from improved CV results. Future research must assess how well-adherent patients with severe OSA and low CV event rates respond to CPAP therapy. In patients who use CPAP for more than four hours each night, CPAP therapy may minimise the risk of MACE and stroke. Additional randomised trials requiring adequate CPAP time adherence are needed to support this perception. Despite the fact that there is no evidence to support the claim that CPAP therapy improves CV outcomes, bias difficulties, CPAP adherence problems, and the patient groups included in each RCT may have made it more difficult to generalise the findings to all patients. Future research is therefore needed to look at these relevant results. Obstructive sleep apnea (OSA) is the most prevalent disorder related to sleep, which is linked to the recurrent collapse of the upper airway during sleeping . OSA affMethods This systematic review seeks to study and assess the use of CPAP in patients with OSA to prevent negative cardiovascular consequences. This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines.Search StrategyThe past 10 years' worth of pertinent articles were chosen after a thorough search of databases including PubMed, PubMed Central (PMC), Science Direct Library, and Google Scholar for articles on Cohort Studies, Systematic Reviews and Meta-Analysis, Observational Studies, Narrative Reviews, and Randomised Control Trials (RCTs). The terms "CPAP," "Obstructive Sleep Apnoea," and "Cardiovascular Events" were used to construct the search, which was then combined using the Boolean operators "AND" and "OR." The published articles were reduced using a mesh technique. The databases checked for article collections are shown in Table Inclusion criteria and exclusion criteria: The studies were picked for inclusion based on the following participant, intervention, and outcome characteristics: Participants: population with OSA symptoms that spans all ages, genders, and ethnicities. The use of CPAP in the aforementioned demographic is the intervention. Papers written and published in English and translated papers, papers focusing on all age groups, papers focusing on CPAP including outcomes focused on cardiovascular events in patients with OSA, RCTs, cohort studies, observational studies, systematic reviews, narrative reviews, meta-analyses and case-control studies. Animal studies patients, translated papers, grey literature, irrelevant studies, and studies that do not address the research question or topic of interest. Studies that focus on a different Population, Intervention, Comparison, or Outcome (PICO) than specified in the review. Case reports or case series, conference abstracts or posters without full-text articles. Studies that do not investigate the specified intervention or comparator(s) of interest. Studies that do not report outcomes relevant to the research question or fail to measure key outcomes. Studies with incomplete or insufficient data extract the required outcome measures. Studies with a high risk of bias or poor methodological quality, as assessed by appropriate quality assessment tools. Studies with incomplete or inadequate reporting of methods, results, or statistical analyses.ResultsUsing the aforementioned search techniques and proper filters, 214 articles from the databases that have been published within the last 10 years (January 2013 to May 2023) were found, utilising Google Scholar's 2013-2023 filter and PubMed's Meta-Analysis, Observational Study, RCTs, Systematic Reviews and Meta-analysis, Human research, English and translated publications filters, respectively. The titles and abstracts of the papers were then used to screen them. The eligibility requirements and availability of the full text were used to filter the articles. Following the removal of duplicates and irrelevant records, the screened articles were subjected to quality assessment using tools such as the Newcastle-Ottawa checklist for case-control and cohort studies, the Cochrane (CCBRT) for RCTs and non-RCTs, and Assessment of Multiple Systematic Reviews 2 (AMSTAR 2) for systematic reviews and meta-analyses. The PRISMA chart, as seen in Figure The studies included in this systematic review are summarised in Table DiscussionPathophysiology of OSAThe underlying causes of OSA and its adverse effects on cardiovascular outcomes are still unknown . SeveralObesity and OSA are interdependent, which leads to a vicious cycle in which the former contributes to weight increase. At the same time, the latter furthers the former's role in the pathophysiology of OSA. In general, two main pathways contribute to weight gain: OSA's detrimental effects on energy expenditure and the dysregulation of the hormones that regulate hunger and fullness. Hormonal alterations promote weight gain by ghrelin-stimulating hunger and leptin resistance-induced low satiety . Among tMechanism of Action of CPAP TherapyCPAP therapy has been shown to improve symptoms and other surrogate outcomes, including blood pressure and glycemic management, by lowering hypoxemic burden and obstructive episodes. Theoretically, CPAP therapy is anticipated to lessen individuals with OSA's risk of cardiovascular events by obstructing the mechanisms mentioned earlier . CPAP haAnalysisWe sought to determine the effect of CPAP on cardiovascular events in this updated systematic review of meta-analysis, RCT, systematic reviews, and meta-analysis, case-control studies and observational studies involving patients with OSA. The main findings of this analysis are (1) there was no significant difference between the CPAP and control groups in the occurrence of MACE at a mean follow-up of 42.6 months; (2) On subgroup analysis, CPAP use was associated with lower risk of MACE; (3) We discovered concerns about the included studies' potential for bias, primarily as a result of participant and staff blinding; (4) We discovered additional concerns about the applicability of the findings, primarily as a result of variations between included studies, including either non-sleepy or sleepy subjects, adherence to CPAP therapy, and the typical follow-up of the included RCTs; OSA can independently increase the risk of cardiovascular events, even after controlling for confounding factors, according to a systematic study conducted by Yingke Zhao et al. and observational study conducted by Yusel Peker et al. ,17. Due Strengths and WeaknessesOne of the key strengths of our analysis is the inclusion of a subgroup analysis based on CPAP adherence. This additional analysis allows us to examine the potential benefits of CPAP therapy when patients consistently adhere to treatment. We found that among the CPAP-adherent subgroup, there was a significant reduction in MACE, suggesting that adherence to CPAP treatment plays a crucial role in achieving positive outcomes. These findings highlight the importance of patient education and support to promote long-term adherence to CPAP therapy. The lack of an overall benefit for CPAP therapy in our analysis should be interpreted while considering certain limitations in the included randomised trials and other research studies. First, the majority of studies have mostly included non-severe OSA. Prior observational studies suggested that patients with severe OSA carry the highest risk of cardiovascular events; hence, the magnitude of the benefit of CPAP could be underestimated by eliminating those patients. Second, the magnitude of benefit from CPAP might differ in primary prevention versus secondary prevention in patients with OSA. Most randomised trials included patients with established cardiovascular events, and high cardiac risk factors, in whom OSA might not play a substantial risk factor compared to lower-risk populations. Therefore, the role of CPAP in the primary prevention of cardiovascular events cannot be determined from the current randomised data. Also, the included studies exhibited heterogeneity regarding patient characteristics, such as age, sex, and comorbidities. Therefore, caution should be exercised when extrapolating the results to broader populations. Future studies should include more diverse patient populations to enhance the external validity of the findings. Additionally, the issue of CPAP adherence poses a challenge in real-world clinical settings. While our subgroup analysis suggests that adherence is associated with improved outcomes, it is essential to recognise that achieving and maintaining adherence can be difficult for some patients. Further research should focus on identifying effective strategies to enhance CPAP adherence, such as personalised patient education, regular follow-up, and addressing barriers to adherence. Our review also identified a potential risk of bias in the included studies, particularly related to the blinding of participants and personnel. Blinding is challenging in CPAP studies due to the nature of the intervention, and the lack of blinding may introduce performance and detection bias. It is crucial for future research to implement rigorous blinding methods and consider alternative study designs, such as randomised controlled trials, to minimise bias and strengthen the evidence base. Finally, many of the included studies suffered poor adherence to CPAP therapy among the included patients. Our subgroup analysis is hypothesis-generating and suggests that adherence to CPAP may play an important role in determining the impact of CPAP on cardiovascular outcomes. We hypothesize that achieving a clinically meaningful reduction in cardiovascular events mandates the application of CPAP four hours or more daily to reverse airway obstruction, hypoxemia and ensuing detrimental mechanisms. In conclusion, our systematic review provides important insights into the impact of CPAP therapy on cardiovascular events and mortality. While the findings suggest a potential benefit, caution is warranted in generalising the results due to the heterogeneity of the included studies and the challenges associated with CPAP adherence. By addressing these limitations and implementing our proposed recommendations, future research can contribute to a more comprehensive understanding of the role of CPAP therapy in improving patient outcomes.LimitationsStatistical heterogeneity in outcome measures of MACE exists due to different study designs, small sample sizes, and variations in study quality and adjustment for confounders. Study populations vary from general CAD patients to specific subsets with MI and revascularization. Future studies should focus on more homogeneous patient groups. Differences in definitions and adherence to CPAP treatment impact treatment effects compared to control groups. Standardized definitions are needed. Risk estimates of individual cardiovascular events could be more balanced due to the small number of studies and variations in event definitions. Summary data from moderate-to-large-sized RCTs show limited events and may not capture the moderate benefits of positive airway pressure (PAP) therapy. More data are needed to detect these effects. Adverse effects of PAP therapy may be revealed with additional data, as some associations suggest harm rather than benefit. Recommendations for future studies: In light of the limitations identified in our review, we propose several recommendations for clinical practice and future research. Firstly, healthcare professionals should prioritise patient education and support to improve CPAP adherence. Overall, better-designed randomised trials are warranted to appreciate the true role of CPAP therapy on cardiovascular events among patients with OSA. Future trials should pursue alternate designs to maximise CPAP adherence rates among participants and, importantly, enrol sleepy patients with OSA who would hypothetically benefit more from CPAP therapy. This may involve providing clear instructions on CPAP use, addressing patient concerns and misconceptions, and offering ongoing support and monitoring. Furthermore, given the potential impact of patient characteristics on treatment outcomes, clinicians should consider individualised approaches when prescribing CPAP therapy. Future research should focus on conducting well-designed RCTs encompassing diverse patient populations and address the limitations of the current evidence. Additionally, investigations into the long-term effects of CPAP therapy, the optimal duration of treatment, and the comparative effectiveness of different CPAP devices and modes of delivery would provide valuable insights into refining treatment strategies. Standardisation is crucial to reduce heterogeneity in study design, CPAP application, sleep evaluation, and event definitions. This will enhance comparability and reliability across studies. focusing on more homogeneous patient groups will enable a more accurate assessment of CPAP treatment effects. Large sample sizes should be considered to adequately power the analysis and detect statistically significant effects on cardiovascular endpoints. Additionally, longer follow-up periods are necessary to accurately assess the clinical benefits of CPAP therapy. Comparative placebo-controlled trials can help reduce bias and provide stronger evidence for treatment effects. Thorough documentation of potential confounders, co morbidities, and clinical variables is essential in cohort studies to account for their influence on prognosis. Homogenous patient populations, such as those with CAD or MI, should be the focus of research to accurately evaluate the treatment effects of CPAP therapy. Increasing sample sizes will provide adequate statistical power for detecting meaningful differences in cardiovascular events. Extending the duration of follow-up will capture long-term outcomes and comprehensively evaluate the clinical benefits of CPAP therapy. Incorporating placebo-controlled arms in trials is important to assess the true efficacy of CPAP therapy and reduce bias. Lastly, establishing standardized protocols, encouraging collaboration and data sharing, and performing sensitivity analyses will enhance the reliability and generalizability of study findings. By implementing these recommendations, future research on CPAP therapy can be improved and provide more robust evidence for its effectiveness. By implementing these recommendations, future studies can address the limitations identified and provide more robust evidence regarding the effectiveness and safety of CPAP therapy in cardiovascular outcomes.Even though our present study indicates that patients with a diagnosis of cardiovascular disease and OSA do not benefit from CPAP therapy when it comes to preventing clinically relevant outcomes like mortality or improving cardiovascular disease, it is essential to remember that the absence of any effect is not equivalent to the absence of an effect. In our evaluation, we highlight several issues with most research, how to read these studies and this meta-analysis. (1) Even though CPAP therapy did not reduce the risk of cardiovascular events, these results should be interpreted cautiously, and further study is required before RCTs involving patients with OSA are designed differently. (2) Long-term follow-up shows a high correlation between CPAP adherence and better outcomes. Additional research should concentrate on incorporating OSA patients who use CPAP for more hours per night as few studies mentioned in the analysis section described that the normal patients were using CPAP only for 3.3 to 3.5 hours per night which might not be enough to unveil the true positive effects of CPAP, so studies where patients have used CPAP for four hours or more than four hours per night should be included. (3) Different OSA phenotypes, including subgroups like sleepy vs. non-sleepy patients, hypoxemic characteristics in patients with moderate to severe OSA, and descriptions of poorer populations using metrics other than the AHI, should all be included in novel RCTs. (4) The majority of studies involved patients from hospital and sleep clinic populations, and future research should include population-based studies to examine the effectiveness in the primary prevention of cardiovascular illnesses.


Muscle regeneration is a physiological process that converts satellite cells into mature myotubes under the influence of an inflammatory environment progressively replaced by an anti-inflammatory environment, with precise crosstalk between immune and muscular cells. If the succession of these phases is disturbed, the immune system can sometimes become auto-reactive, leading to chronic muscular inflammatory diseases, such as myositis. The triggers of these autoimmune myopathies remain mostly unknown, but the main mechanisms of pathogenesis are partially understood. They involve chronic inflammation, which could be associated with an auto-reactive immune response, and gradually with a decrease in the regenerative capacities of the muscle, leading to its degeneration, fibrosis and vascular architecture deterioration. Immunosuppressive treatments can block the first part of the process, but sometimes muscle remains weakened, or even still deteriorates, due to the exhaustion of its capacities. For patients refractory to immunosuppressive therapies, mesenchymal stem cells have shown interesting effects but their use is limited by their availability. Stromal vascular fraction, which can easily be extracted from adipose tissue, has shown good tolerance and possible therapeutic benefits in several degenerative and autoimmune diseases. However, despite the increasing use of stromal vascular fraction, the therapeutically active components within this heterogeneous cellular product are ill-defined and the mechanisms by which this therapy might be active remain insufficiently understood. We review herein the current knowledge on the mechanisms of action of stromal vascular fraction and hypothesise on how it could potentially respond to some of the unmet treatment needs of refractory myositis. Muscle regeneration involves a sequence of tissue repair mechanisms regulated by both pro- and anti-inflammatory immune cells.Myositis pathomechanisms are not fully understood but may result from chronic exposure to immune cells and cytokines, leading to destruction and mis-repair of muscle, with fibrosis and vascular architecture disturbance.Therapeutic options for inflammatory myopathies are predominantly based on immunosuppressive treatments, which are sometimes insufficient to regulate the different features of these complex pathologies.Adipose tissue-derived stem cells and stromal vascular fraction have immunomodulatory, anti-fibrotic, proangiogenic and regenerative properties that could be exploited for the treatment of refractory or relapsed myositis.However, the mechanisms behind these effects are still insufficiently understood and more preclinical studies are required before their clinical use.Does repeated acute muscular destruction trigger chronical autoimmune inflammation, or is auto-immunity responsible for muscle destruction in myositis?In myositis, how does chronicle inflammation affect adipose-derived cells capacities?Will adipose stem cells replace muscle stem cells and directly participate in tissue regeneration, or rather have a supporting role for immune and local stem cells?The mechanisms of muscle regeneration following injury are now well-known and involve both muscle and immune cells, through a regulated process . A disruFor these patients, cell therapies have sometimes shown long-term beneficial effects. Autologous hematopoietic stem cell transplants, which have been used to replace auto-reactive immune systems, have improved patients’ conditions, and even allowed some of them to enter into remission. These therapies generally seem to be safe, but can be complicated by severe or even life-threatening iatrogenic infections due to myeloablative conditioning regimens –10. MoreAdipose tissue is another source of MSC. They can be extracted safely and in large quantities from a lipoaspirate by enzymatic digestion or mechanical isolation for Stromal Vascular Fraction (SVF), followed by replicative cultures of adherent cells for Adipose-Derived Stem Cells (ADSC) . If ADSCIn order to evaluate the potential of SVF as a treatment for refractory myositis, we first summarise here the physiological mechanisms of muscle regeneration and the pathological mechanisms involved in myositis. Next, we address the main features of these diseases through the known mechanisms of action of this cell therapy. Last, we discuss its clinical relevance by analysing results from various clinical trials.Muscle regeneration after trauma is a process that involves both immune and muscular cells in order to restore normal muscle function. At first, satellite cell activation and proliferation accompanied by inflammation, followed by a progressive decrease of inflammation under the influence of anti-inflammatory cells, which stimulate muscle progenitor cell differentiation and tissue remodelling .At the earliest stage of regeneration after injury, muscle damaged cells release Damage-Associated Molecular Patterns (DAMP) , which l+ and CD4+ T cells appear at the lesion site and can be detected for up to ten days [+ T cells pursue the task of macrophages and neutrophils, by releasing many cytokines which amplify the recruitment of leucocytes and by acting on extracellular matrix remodelling to speed up cellular debris elimination [+ T cells seem to be recruited a little later than CD8+ T cells [Around three days after injury, both CD8ten days . CD8+ T mination . CD4+ T  T cells . They diThe large amount of secreted cytokines modulates the environment of the injured site and triggers muscular regeneration . Fu et aWhen the clearing of damaged cells ends, the naive T cells recruited polarise into Th2 cells, which release anti-inflammatory cytokines (IL-4 and IL-13) . These c+-mediated cytotoxicity, and nonimmunological mechanisms [+ and CD8+ T cells can be activated by muscle cells, which act directly as antigen presenting cells, but also indirectly through dendritic cells (DC) detected in muscular infiltrate during myositis [+ or CD20+ B cells and CD138+ plasma cells and by the expression of B-cell activating factor [The myoregeneration process relies on the presence of functional satellite cells in the muscle and the environmental agents that control at different phases the proliferation, differentiation and fusion of these cells into myotubes . Among tchanisms , 55. Themyositis , or TLR myositis , 57. Theg factor . Myositig factor . The patg factor . Furtherg factor . This pag factor .Fig. 1SkAnti-inflammatory cells are also present in myositis muscle and some of them take part in the pathomechanism. If the Th2 cytokine IL-4 overexpressed in myositis seems inversely correlated with the severity of muscular destruction, as evidenced by muscular enzyme levels in the sera , anti-inIf the pathogenic triggers of myositis have not yet been identified, partially due to a lack of spontaneous animal models, the hypothesis of an immune system defect which is solely responsible or even at the origin of the disease is controversial, especially in IBM , 74. MusMyositis represents a heterogeneous group of diseases which involve immune and non-immune mechanisms. In these diseases, the immune system acts on both muscle degeneration and regeneration, with muscle progenitor cell stimulation by cytokines. While suppressing myositis may appear as an effective solution to stop or to slow down the disease, this can be insufficient or even aggravating sometimes, due to non-immune mechanisms or regenerative defects.Most of the treatments used in myositis target the inflammatory actors. Glucocorticoids are the most current therapeutic approach, alone as a first-line treatment or associated with other immunosuppressive molecules in refractory patients . These aCell therapies are occasionally used to treat patients with refractory PM or DM, but very few cases have been reported. As stated above, hematopoietic stem cell autologous transplantation, used to replace auto-reactive immune system after its depletion, has shown benefits but with a high risk of side effects –10. MSC The first clinical study using MSC was published in 2011 by Wang et al. and reported the case of 10 patients with refractory PM or DM, according to Bohan and Peter criteria . After tn = 37 patients) or without (n = 44 patients) allogeneic UC-MSC injections in patients with PM or DM [Lai et al. published the only controlled clinical trial, comparing conventional therapy (6 months of corticosteroids and immunosuppressors) with  and mobility 3 months after treatment, but no significant change in blood laboratory values . The patPharmaceutical and biological treatments have evolved and now allow to treat most of patients with myositis. After multiple lines and associations of treatment, some patients with PM or DM remain refractory and more often those with IBM. In the latter case, new treatments under evaluation target more specifically muscle degeneration, through metabolic or regulatory pathways, but the expected effect is not always obtained. Conversely, MSC therapies have shown interesting results in myositis, but their harvest and preparation are not simple and clinical studies remain rare. SVF, which has similar effects, could be an alternative, provided its clinical efficacy is proved through robust clinical trials. Two of them are about to start to study the safety of SVF in IBM .SVF isolation consists in adipocyte elimination through enzymatic or mechanical procedures , 91. DueToday, SVF is widely used and frequently compared to ADSC in both regenerative medicine and immune/inflammatory disorders and presents significant advantages. Indeed, SVF extraction is simpler and quicker than ADSC expansion and does not present the risks associated with long-term cell culture . Combined with a permissive regulatory framework in some countries, the use of SVF has regrettably been diverted by private clinics with little interest in studying the efficacy and mechanisms of action of this therapy, which has slowed its development. This was particularly observed in the United States, which had an unusually low number of publications on the topic  whereas The use of SVF has been reported in many indications and it may represent a promising adjunctive therapy for patients with diseases for which current and conventional therapies are inadequate. The variety of these indications was recently reviewed by Andia et al. who analysed 71 published clinical studies evaluating SVF . HoweverSome recent studies reviewed adverse events in patients receiving “unproven or unapproved” stem cell therapies reported in scientific publications, clinical case reports and also mass media publications, and showed an increased number of severe complications and hospitalisations compared to conventional therapies , 101. CoIntramuscular injections of SVF were clinically used as a local route for the treatment of muscle sequelae , 104, alAs seen above, intramuscular injection of SVF is known to be safe and has promising clinical effects in both autoimmune and muscular diseases. Its potential interest in myositis treatment is based on four properties, but mechanisms of action are not fully known Fig. .Fig. 3StFirst, the immunomodulatory effect of SVF is supported mainly by three cell populations: AD-MSC, macrophages and Treg cells. AD-MSC immunomodulatory capacities are similar or higher to those of BM-MSC according to different studies , 111 andADSC and SVF can also act on fibrosis via their immunomodulatory effects. Indeed, by reprogramming immune cells into anti-inflammatory cells, they increase the expression of IL-10, which presents several anti-fibrotic properties: inhibition of neutrophil and macrophage invasion and ROS release , down-reIndeed, SVF is known to express high levels of IGF1, IL-8, Platelet-Derived Growth Factor-beta (PDGFβ), bFGF and VEGF, and to have robust angiogenic and vasculogenic activities demonstrated both in vitro and in vivo in a hind limb ischaemia model . These gSVF, through its immunomodulatory properties, acts on both chronic inflammation and muscle repair via cytokine release (mainly IL-4 and IL-13). Moreover, growth factors secreted by stromal cells may have a positive effect on muscle regeneration, and some of them are currently under evaluation in the management of muscle disorders, such as sarcopenia . But oneMSC-based therapies have shown interesting effects in the treatment of refractory myositis, but their clinical use remains limited, especially for those extracted from adipose tissue. However, SVF, easily harvested from this tissue, could be beneficial for patients thanks to its properties combining an immunomodulatory effect and a response to the main muscular complications of myositis. While published cases report only IV infusion of MSC in myositis treatment, IM injection of SVF seems to be an interesting alternative, providing both local and systemic effects. Taken together, the evidence reviewed here seems to predict a potential benefit of SVF in myositis treatment. However, these findings also highlight the need for preclinical studies and clinical trials to better understand the mechanisms of this therapy and to optimise the practical modalities to ensure its safety and efficacy.


This study focused on identifying cancer type-specific genes, which are crucial for improving the detection, diagnosis, and treatment of various types of cancer. We used a network biology framework to explore the expression of transcription factors in different types of cancer. By comparing gene networks in normal cells with those in cancer cells, we were able to identify cancer type-specific genes. This offers a resource for understanding transcriptional networks across various cancer types.Identifying cancer type-specific genes that define cell states is important to develop effective therapies for patients and methods for detection, early diagnosis, and prevention. While molecular mechanisms that drive malignancy have been identified for various cancers, the identification of cell-type defining transcription factors (TFs) that distinguish normal cells from cancer cells has not been fully elucidated. Here, we utilized a network biology framework, which assesses the fidelity of cell fate conversions, to identify cancer type-specific gene regulatory networks (GRN) for 17 types of cancer. Through an integrative analysis of a compendium of expression data, we elucidated core TFs and GRNs for multiple cancer types. Moreover, by comparing normal tissues and cells to cancer type-specific GRNs, we found that the expression of key network-influencing TFs can be utilized as a survival prognostic indicator for a diverse cohort of cancer patients. These findings offer a valuable resource for exploring cancer type-specific networks across a broad range of cancer types. Sequence-specific TFs and chromatin modifying enzymes provide constraints to dictate diverse gene expression programs during development. In this highly choreographed process, TFs bind sets of genes that define cell type-specific gene regulatory networks (GRN), which are conditionally expressed following chromatin remodeling. The processes that are critical to maintaining normal cellular function can be disrupted or hijacked during tumorigenesis or neoplastic states by aberrantly controlling transcription. Overlapping gene expression patterns between normal and cancer cells and activation of developmental Directed in vitro differentiation of stem cells has been a focus of biologists to derive cell types for the purpose of studying development, regenerative medicine, and drug screening. An assortment of lineages have been reprogrammed to an induced pluripotent (iPS) stem cell state ,2,3,4,5,To decipher the molecular mechanisms that drive malignancy in a cell- and tissue-specific manner, it is crucial to understand the dominant oncogenic TFs that distinguish cancer cells from normal cells. As oncogenic transformation typically involves aberrant activation of primitive developmental programs, a process that is mirrored during the acquisition of iPS cells, it is plausible that tools that faithfully identify cell-type defining TFs can be successfully applied to reverse engineer cancer cells to a benign or drug-sensitive fate. Identifying GRNs across various types of cancer can aid in understanding oncogenic mechanisms and serve as targets for cancer therapy, making it highly relevant in the field of oncology. Despite a compendium of studies which have generated expression datasets for a variety of cancer types, GRNs that define cancer types have not been fully elucidated.Here, we utilized the core engine of a network biology platform  to identThe resulting platform, which we generated using a compendium of publicly available cancer expression datasets, is a robust tool to identify cancer type-specific GRNs, which are comprised of multiple TFs. We describe the performance of the platform and identify core TFs and GRNs for multiple cancer types. We also compared normal tissue and cell types with cancer type-specific networks to identify candidate oncogenic reprogramming factors, candidate therapeutic targets, or biomarkers. Findings from this study also show that the expression of network-influencing TFs can predict the survival of cancer patients. Overall, these findings provide a resource to study cancer-specific transcriptional networks.Generation of metadata file (training sample table)To obtain the full training datasets, GEO was used to search for expression profiles of 17 types of cancer  using th2.Pre-processing of training datahttps://github.com/KidderLab/CancerTFs (accessed on 10 August 2023) for additional training details. The pre-processing of both the training data and the query data to be analyzed by CellNet was performed using the same methodology.Pre-processing was performed using CellNet as previously described ,25,26. P3.GRN construction, training, and validation:This step generated cancer type-specific gene regulatory networks (GRNs). The evaluation of classifiers developed through GRN construction takes place in this step. The process involves dividing the training data equally into two sections. One part is employed to train the CellNet model, while the other part serves as validation data. The generated results enable the construction of heat maps and precision–recall curves, thereby facilitating the assessment of the classifiers.Using CellNet on the processed data, we generated several outputs: first, the classification score, which provides insight into the extent to which the expression profiles of the query samples resemble each of the reference cancer/tumor types. Secondly, the GRN Status, which serves as a metric to assess the level of establishment of cancer/tumor-specific GRN within the sample. Finally, a ranked list of transcription factors (TFs), whose expression modulation has the greatest probability of driving the desired fate change, referred to as the network influence score (NIS).4.Precision recall curvesThe performance of the classification model was evaluated using a precision versus sensitivity plot, where precision represents the fraction of correctly classified positive samples, and sensitivity represents the fraction of all positive samples that were correctly classified for a specific cancer type, with each point on the plot representing the classification score at which these metrics were calculated. Precision and sensitivity were calculated using the number of true positive calls divided by the number of positive calls and the sum of true positives and false negatives, respectively.To obtain query datasets to compare to the trained cancer data, GEO was used to search for expression profiles of normal tissues  using thEnrichr , which fKM-plotter ,30, the p-values. The differential survival rates were visualized using Kaplan–Meier survival plots. We used the KM-plotter’s auto-select best cutoff feature, which calculates all possible cutoffs between the lower and upper expression quartiles. Each cutoff was independently assessed using Cox regression. We adjusted for multiple hypotheses testing using the false discovery rate (FDR), accepting only results with an FDR of less than 10%. The cutoff with the smallest p-value was employed for the final Kaplan–Meier plot.The survival curves partition patient outcomes into two groups based on low (black) and high (red) gene expression levels. Cox proportional hazards regression analyses were used to study the link between gene expression and overall survival. KM-plotter ,30 was uThe cancer dependency database  was usedWe utilized a computational biology platform , which uGenes whose promoters are bound by TF were derived from the gold standard ChIP-Seq data from the ENCODE project , the EscThe classifier performance was assessed using precision sensitivity curves for each gene expression cancer type classifier as previously described ,25 Figu. The meaWe also assessed the cancer type-specific networks’ structural characteristics, including each GRN’s node and edge counts , their sThe dataset that was employed to train CellNet and create the classifiers consists of expression data collected from primary tumor samples that come from 17 different types of cancer. Normal cell and tissue types were used as query datasets to assess the expression differences between cancer and normal tissues. We applied this classification strategy to identify key TF regulators that distinguish normal cells from cancer cells. Example classifications include normal adrenal, lung, and thyroid tissue classified as adrenal, lung, and thyroid, respectively, and reached >90% GRN status A, and noThe barplots in Additionally, neurons are classified as brain cancer or glioblastoma, and the uterus is classified as uterine cancer. Uterine tissue is comprised of various cell types, such as endometrial tissue cells , fibroblasts/stromal cells, smooth muscle and endothelial cells, and immune cells. As such, the uterine tissue cellular composition partially overlaps other organs resulting in a slightly lower GRN status (93%). When we applied this strategy to a variety of normal equivalent cells, we found that they were largely classified as their tumor counterpart  and reacNetwork influencing genes within GRNs that distinguish normal cells from their cancerous counterparts  are shown in Enrichr  was usedA detailed examination of all studied cancer types is presented in A further exploration of genes enriched in cancer cells relative to normal cells  using KaTo gain further insight into GRNs of prostate cancer, candidate core transcriptional regulatory factors were selected based on protein–protein interactions within the GRN  with eleSIN3A, which is a scaffolding protein associated with the nucleosome remodeling domain complex , and CTCHere, we implemented an algorithmic platform  to identTFs regulate cell identity and may be useful in engineering cell models of transformation and tumor formation. We propose that identification of genes whose expression is enriched in cancer cells relative to normal cells may serve as biomarkers of tumorigenesis or potential therapeutic targets. While predicting the expression of genes within GRNs is challenging, our approach simplifies complex networks to prioritize key TFs that regulate cell identity. The study also aimed to understand how GRNs differ between normal cells and cancer cells, as these differences can provide valuable information about oncogenic networks that drive tumorigenesis. By conducting a comparative analysis of GRNs between normal and tumor cells, this study identified distinct gene expression patterns. Our results also provide a rich resource to explore and understand expression patterns that exist in a wide range of cancer types. By mining cancer type-specific GRNs across a broad range of cancer subtypes, it may be possible to identify common patterns and mechanisms of tumor formation, which could lead to the development of more effective treatments for cancer.The study utilized a classification strategy to identify cancer type-specific GRNs and key TFs that distinguish normal cells and cancer cells. By using normal cell gene expression data as the query and contrasting it with GRNs generated from cancer cells, we were able to identify network-influencing genes within cancer GRNs.The examination of differentially expressed genes between normal and cancer cells and the structural characteristics of these cancer type-specific GRNs may point towards potential therapeutic targets or biomarkers. These alterations could potentially play a critical role in disease onset or progression. Targeting these hubs could hinder cancer progression and improve treatment outcomes by disrupting oncogenic pathways or serving as models for oncogenic transformation in various cancer types. These findings lay the groundwork for exploring how targeting these may impede cancer progression and improve treatment outcomes.Here, we conducted a comprehensive exploration and analysis of network-influencing genes within cancer type-specific GRNs, contrasting the gene expression data of normal cells with the GRN of various cancer cells. Our results revealed distinct TFs in different cancer types, providing insights into the gene regulatory alterations in cancer cells. Using Enrichr  and UMAPIn this study, further exploration of the GRNs of prostate cancer identified key transcriptional regulatory factors, CTCF and SIN3A. These two chromatin constituents exhibited overexpression in prostate cancer compared to normal tissue, and the low depmap dependency scores of these genes highlight their essential role in prostate cancer cell proliferation, suggesting their potential as crucial regulators of gene expression within prostate cancer cells. These findings set the stage for further exploration of the roles of CTCF and SIN3A in prostate cancer progression and resistance to treatment.Expression of the chromatin insulator, CTCF, which is involved in transcriptional regulation and chromatin loop formation, is overexpressed in prostate cancer relative to normal prostate tissue . ProstatOur results also highlight the GRN performance measures of gene targets per TF and the number of regulators per target gene. Transcription factors with more targets are likely to have a more extensive regulatory role. In contrast, transcription factors with fewer targets can be associated with increased specificity. The number of targets per TF can have an impact on the performance of the platform, as it affects the accuracy of the predicted regulatory networks. The number of targets per TF is a trade-off between specificity and accuracy in predicting regulatory networks with the model, where TFs with more targets are likely to have a broader regulatory role but may pose challenges in predicting specific interactions, while TFs with fewer targets may be more specific but are harder to predict using gene expression data alone. Our results leverage insight from the complex interplay between transcription factors and their targets to develop GRN models for the identification of cancer type-specific genes. By unraveling oncogenic transcriptional networks across various cancer types, it underscores the potential of this approach in revealing critical transcriptional regulators.Moreover, in our analysis, we discovered that different cancer types exhibited distinct numbers of nodes within their GRN . This vaIn conclusion, this study presents GRN models for the identification of cancer type-specific genes. By providing a resource for investigating the oncogenic transcriptional networks across a wide spectrum of cancer types, this study underscores the potential of utilizing this approach to reveal critical transcriptional regulators involved in various cancers.


Piriformospora indica, have been shown to have growth-promoting and disease-protection abilities  associated with the synthesis of cyclic lipopeptides (CLPs) in a phytopathogenic bacterium Pseudomonas fuscovaginae UPB264 that causes sheath brown rot disease in rice. The authors have obtained a single-contig genome of the UPB264 and identified that the bacterium encodes novel CLPs, asplenin, in addition to the previously reported CLPs, syringotoxin and fuscopeptin. Using the mutant strains, fuscopeptin and syringotoxin are important for the bacterium causing rice sheath rot disease. In contrast, asplenin and syringotoxin are important for bacterial swarming motility and antifungal activity. Syringotoxin has been reported to have antifungal activity against sheath blight pathogen Rhizoctonia solani. The study emphasises the characterisation of putative BGCs is an important area of research, which would lead to the identification of novel bioactive molecules for potential exploitation for plant growth promotion and disease control.Li et al. report that a Priestia megaterium strain JR48, isolated from the vegetable field, has a plant-growth-promoting and biocontrol effect. The data reflected that bacterial Treatment not only enhances the Chinese cabbage’s growth but also prevents the plants from black rot disease caused by Xanthomonas campestris pv. campestris 8004 (Xcc) infection. Notably, induced expression of various defence-related genes, including pathogenesis-related (PR) genes, enhanced callose deposition, salicylic acid (SA) accumulation, and hydrogen peroxide, were observed in the JR48-treated plants. Overall, the study emphasizes the importance of salicylic acid (SA)- mediated defence in the biocontrol ability of JR48.One of the important attributes of beneficial microbes is their ability to induce host immune responses and prevent disease establishment by phytopathogens. It is important to understand the defence-priming ability of the beneficial microbes to utilise them for disease control. Zhu et al. provide the current understanding in this field and elaborate on how quorum quenching is effective in countering pathogen growth and attenuating virulence in crop plants. The quorum quenchers either function through competitive inhibition of the active site or physical degradation of the signalling molecules. They are primarily considered to have fewer side effects on non-target micro-organisms. An additional advantage of using quorum quenchers is that, unlike antibiotics, for which there is selection pressure in bacteria to develop resistance, it is challenging to build tolerance against quorum quenchers. The review not only elaborates on various applications of quorum quenchers in agriculture but also discusses their exploitation in controlling aquacultural pathogens, human pathogens, and biofouling mitigation. The article advocates that it is important to investigate quorum quenching molecules’ side effects on non-target organisms, particularly whether they can alter the colonisation of beneficial microorganisms. The special issue on utilising microbiome for controlling phytopathogens provide novel approaches for biocontrol of diseases.Notably, plant-associated microbes continuously interact with the host plants and other co-having microbes in a hostile environment. They have intricate ability to communicate with each other using quorum sensing molecules. Extensive progress has been made in understanding the quorum-sensing mechanism and exploring whether using quorum-quenching molecules could prevent phytopathogens from establishing disease. All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication.