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Farming and sedentism first appear in southwest Asia during the early Holocene and later spread to neighboring regions, including Europe, along multiple dispersal routes. Conspicuous uncertainties remain about the relative roles of migration, cultural diffusion and admixture with local foragers in the early Neolithisation of Europe. Here we present paleogenomic data for five Neolithic individuals from northwestern Turkey and northern Greece, spanning the time and region of the earliest spread of farming into Europe. We observe striking genetic similarity both among Aegean early farmers and with those from across Europe. Our study demonstrates a direct genetic link between Mediterranean and Central European early farmers and those of Greece and Anatolia, extending the European Neolithic migratory chain all the way back to southwestern Asia.

Cytomegalovirus (CMV) infection or reactivation in immune-compromised individuals can lead to a wide range of severe complications including hepatitis. However, its relation with immune checkpoint inhibitors (ICIs) induced hepatitis (ICI-hepatitis) and tumor responses in advanced melanoma patients remains unclear. Hundred and ninety metastatic cutaneous melanoma patients (mCM) who received ICI treatment, with CMV IgG or IgM information available at baseline, were included in the study (Cohort 1). Clinical characteristics and immune cell count in the blood were retrieved from medical records. In addition, anti-CMV IgG and IgM were measured in pre and on-treatment serum samples from 49 advanced skin cancer patients using ELISA (Cohort 2). In the event of a positive anti-CMV IgM, further analysis with PCR was performed. Univariate and multivariate analysis was used to assess the relationship between CMV IgG or IgM and ICI-hepatitis tumor outcomes. Twenty-one patients (11%) developed hepatitis during ICI treatment (Cohort 1). ICI-hepatitis was significantly associated with disease control rate (DCR; p  = 0.017) and longer progression-free survival (PFS; p  = 0.008) in mCM patients. Detection of CMV IgG or IgM antibodies were not associated with ICI-hepatitis ( p  > 0.05). However, increased CMV IgG values at baseline correlated with disease progression ( p  = 0.047) and shorter PFS ( p  = 0.081). In addition, increased CMV IgG values were associated with reduced levels of monocytes ( p  = 0.005), eosinophils ( p  = 0.062), and neutrophils ( p  = 0.065) in the blood. In summary, anti-CMV IgG or IgM in the blood may not be associated with ICI-hepatitis, but high anti-CMV IgG at baseline indicates poor outcomes in ICI-treated mCM patients.

Health-related-quality-of-life is frequently reduced following intensive care treatment. Unwarranted or unwanted therapeutic interventions should be avoided at all costs. Since COPD patients are often faced with difficult decisions, an assessment was made of their desire for disease education. Our aim was to identify patients understanding of their disease and what their attitudes are towards different treatment options and whether this correlates to demographic factors. The COPD-Assessment-Test (CAT) was used to measure subjective disease burden. The COPD-Questionnaire (COPD-Q) was used to assess subjects' own knowledge of their disease. In addition, a specifically designed questionnaire was used to assess patient's subjective level of desire to be educated on COPD-specific topics. A multiple linear regression analysis was performed to identify the demographic factors associated with a greater desire for disease-specific information. 127 patients (67.2±8.8 years) were prospectively enrolled. Mean CAT score was 21.3±8.9 (95% CI:1-40). The desire for medical consultation was highly individual. In terms of vaccination, 31.5% of patients wished for more information while 34.6% wished for less. This also held true for information on long-term pharmacological therapy (29.1% vs 30.7%, respectively). Information on behaviour in case of emergencies as well as smoking cessation were wished for 38% and 42% of patients, respectively. Results of the COPD-Q showed that subjects were well-informed about specific topics (vaccination, etiology, emergency-inhaler) and less informed about long-term pharmacotherapy. In linear regression analyses, age (p=0.086), sex (p=0.906), education (p=0.833), health literacy (p=0.336) and burden of disease (p=0.296) did not influence patients´ desire for disease-specific information. Based on our cohort, COPD patients wish for more medical information related to behaviour in emergency situations and smoking cessation. The desire for education on disease-specific topics did not naturally correlate with demographic characteristics. The provision of medical information to patients remains a highly individualized and essential part of patient care. German Clinical Trials Registry (DRKS00022109).

Non-invasive ventilation (NIV) is vital for managing chronic hypercapnic respiratory failure in COPD patients, yet the impact of handling issues like mask compliance triggering hospitalisations is often underestimated. A prospective, monocentric observational study was performed in COPD patients hospitalized for acute exacerbation with established home NIV therapy. Various questionnaires (CAT, SRI, BORG) and blood gas analysis were used to determine the severity and cause of respiratory insufficiency. 59 patients (mean age 66.57 years ± 9.42, mean BMI 26.99 ± 8.63) were included. 54.24% were female (n=32). The overall cohort had a mean exacerbation rate of 2.24 ± 1.48 within the last 12 months prior to admission. Patients were divided into 4 sub cohorts based on their exacerbation trigger: infection (n=25), handling problem (n=12), non-infection (n=8), and an overlap cohort with evidence of both handling problem and non-handling problem (n=14). Significant differences exist when comparing exacerbation rate (handling-issue cohort: 2.58 ± 1.68 vs infection cohort: 1.76 ± 1.13, p=0.043), total hospital stay (handling-issue cohort: 9.25 ± 5.94 days vs infection cohort: 12.96 ± 5.76 days, p=0.039). There was no significant difference in health-related quality of life measured by the SRI (Summary Score 40.6±12.3 vs 46.8±14.2; p=0.103). In our study, we were able to show that handling problems are associated with frequent exacerbations, cause long hospitalisation periods and are associated with a reduced aspects of quality of life. Patient education and training should therefore play a key role in the treatment of patients.

Background The increased availability of myositis autoantibodies represents new possibilities and challenges in clinical practice (Lundberg IE, Tjärnlund A, Bottai M, Werth VP, Pilkington C, de Visser M, et al. 2017 European League Against Rheumatism/American College of Rheumatology classification criteria for adult and juvenile idiopathic inflammatory myopathies and their major subgroups. Ann Rheum Dis. 2017;76:1955–64. https://doi.org/10.1136/annrheumdis-2017-211468 .). The aim of this study was to perform a retrospective data analysis of patient cases with positive myositis autoantibodies to analyse their significance in routine rheumatology practice. Methods A monocentric analysis of all the orders used to determine myositis autoantibodies from July 2019 to May 2022 in the Department of Rheumatology, Krankenhaus Porz am Rhein, Cologne, Germany, was carried out. Results In the defined time interval, a total of 71,597 laboratory values for the antibodies mentioned above were obtained. A total of 238 different positive autoantibodies ​​were detected in 209 patients. Idiopathic inflammatory myopathy was diagnosed in 37 patients (18%), and inflammatory rheumatic diseases other than idiopathic inflammatory myopathy were diagnosed in 90 patients (43%). No inflammatory rheumatic disease was diagnosed in 82 patients (39%). General clusters of clinical manifestations were observed. Conclusions In our cohort, we were able to show that a relevant proportion of patients with positive myositis antibodies did not have idiopathic inflammatory myopathies or inflammatory rheumatic diseases. This finding indicates the importance of myositis autoantibodies in this group of patients. However, further studies on the course of symptoms and examination results in patients without inflammatory rheumatic diseases and with positive myositis antibodies are necessary.

Objective Patient involvement in scientific research is becoming increasingly important to ensure a patient-centered approach to medicine. The objective of this study is twofold: firstly, to ascertain patients’ perspectives on adherence to therapy and secondly, to integrate this information into a systematic review (SR) on interventions to improve adherence in chronic obstructive pulmonary disease (COPD). Methods In parallel with the SR, two focus group interviews with a COPD self-help group were conducted using semi-structured interview guidelines. The interviews were analyzed using computer-assisted qualitative content analysis according to Kuckartz with the aim of complementing the results of the systematic literature review and to develop propositions for further scientific use. Results The first focus group interview comprising 321 codes included 14 (mean age 67.7 ± 6.8 years; 71.4% female) and the second interview comprising 139 codes included 10 (mean age 68,5 ± 8,2 years; 50% female) patients. Ten categories of the content analysis informed the logic models and the applicability analysis of the SR and six propositions representing the patient’s perspective were developed for further scientific use: Main themes were (I) Enhancement of patient’s self-efficacy (II) Access to trusted medical information (III) Patient-physician relationship (IV) Measures to improve adherence (V) Sociocultural/medical environment (VI) Methods to measure adherence. Conclusion The inclusion of the patient perspective in an SR can be successfully achieved by conducting focus group interviews. Multimodal measures aimed at enhancing patient’s self-efficacy helping them to achieve individual goals reinforces adherence to therapy from a patient’s perspective.

Background Non-invasive ventilation (NIV) is a well-established treatment for chronic hypercapnic respiratory failure (CHRF). While studies have demonstrated benefits for mortality, hospitalization rates, and health related quality of life (HRQL), evidence is particularly sparse regarding HRQL determinants in the older population. Methods In a prospective, monocentric observational study, HRQL was assessed using the established Severe Respiratory Insufficiency Questionnaire (SRI). The study was prospectively registered in the German Clinical Trials Register on 17 June 2015 under the registration number DRKS00008759. Patients were categorized into two age-based groups: older patients (≥ 65 years) and younger patients (< 65 years). Multiple linear regression analyses were used to analyze factors on HRQL, including SRI scores, anemia, autonomy impairment, exacerbation history and other factors. Results 237 Patients with COPD with CHRF receiving NIV therapy were included. The mean SRI summary score was 49.9 ± 16.8. with 23.2% ( N  = 55) suffering from anemia and 36.7% ( N  = 87) experiencing  ≥  2 exacerbations annually. Autonomy impairment was observed in 49.4% ( N  = 117) of patients. The updated Charlson Comorbidity Index (uCCI) was 2.2 ± 1.86. No significant differences were found in SRI Summary Scale scores between age groups ( p  = 0.581), but notable disparities were present in the uCCI ( p  = 0.014). Multiple regression analysis revealed a negative association of exacerbation history (Young group: -9.2; 95% CI = -14.8/ -3.55 vs. Older group: -6.17; 95% CI = -11.91/ -0.43) and level of autonomy impairment (e.g. Level of Care 2 Young group: -13.91; 95% CI = -21.4/ -6.43 vs. Older group: -14.94; 95% CI = -22.64/ -7.24) on SRI scores with age-related differences. Anemia only had a negative association on the SRI scores in younger patients with COPD (Young group: -7.9; 95% CI = -14.0/ -1.75 vs. Older group: -1.78; 95% CI = -9.21/ 5.65). Discussion Frequent exacerbations and a higher level of autonomy impairment had a negative association on HRQL across all ages. However only higher levels of impairment (≥ 2) have a detrimental impact on older patients. Anemia was a negative HRQL factor in younger patients, where it was more prevalent. Overall, HRQL was found to be comparably favorable in both older and younger patients, despite age-specific differences in influencing factors. Registration of the clinical trial The study from which the data were analyzed was prospectively registered in the German Clinical Trials Register (DRKS00008759) on June 17, 2015.

Interstitial lung disease (ILD) encompasses a heterogeneous group of diseases, including idiopathic interstitial pneumonia and lung diseases associated with environmental/ occupational exposures or systemic diseases.1 Connective tissue disease (CTD) is one of the common systemic disorders associated with ILD.2 Moreover, growing evidence has underscored a significant lifetime risk of ILD development in CTD.3 However, diagnostic delay is a common problem for patients with fibrotic ILD.4 This is further complicated since a subset of patients present with progressive pulmonary fibrosis (PPF), which is characterized by a rapid deterioration in symptoms, decline in lung function, or progressive fibrosis on high-resolution computed tomography (HRCT).5 Moreover, PPF is associated with a reduction in quality of life and high morbidity and mortality.2 Since no serum biomarkers have been validated for monitoring disease progression, scores based on clinical examination, HRCT, and pulmonary function testing (PFT) parameters have been developed to assess the disease progression.6 The definition of PPF has not been clear for a long time, and the literature contains variously used references.7 Recently, the American Thoracic Society (ATS), European Respiratory Society (ERS), Japanese Respiratory Society (JRS), and Asociación Latinoamericana de Thorax (ALAT) published a guideline with new reference values for the definition of PPF.8 In the present study, we examined data from 50 patients with confirmed CTD-associated 1LD (CTD-ILD) and described the course of these patients. PATIENTS AND METHODS This retrospective longitudinal study was performed at the Cologne Merheim Hospital, Kliniken der Stadt Köln gGmbh, Faculty of Health/School of Medicine, Witten/Herdecke University, Department of Pneumology. According to PFT and HRCT criteria, 23 (46%) patients met the criteria for PPF (Table 1). [...]clinical, functional, and radiologic characteristics and differences between patients with and without PPF were compared.

The human T-cell leukemia virus type 1 (HTLV-1)-encoded transactivator and oncoprotein Tax-1 is essential for HTLV-1 replication. We recently found that Tax-1 interacts with transcription elongation factor for RNA polymerase II 2, ELL2, which enhances Tax-1-mediated transactivation of the HTLV-1 promotor. Here, we characterize the Tax-1:ELL2 interaction and its impact on viral transactivation by confocal imaging, co-immunoprecipitation, and luciferase assays. We found that Tax-1 and ELL2 not only co-precipitate, but also co-localize in dot-like structures in the nucleus. Tax-1:ELL2 complex formation occurred independently of Tax-1 point mutations, which are crucial for post translational modifications (PTMs) of Tax-1, suggesting that these PTMs are irrelevant for Tax-1:ELL2 interaction. In contrast, Tax-1 deletion mutants lacking either N-terminal (aa 1–37) or C-terminal regions (aa 150–353) of Tax-1 were impaired in interacting with ELL2. Contrary to Tax-1, the related, non-oncogenic Tax-2B from HTLV-2B did not interact with ELL2. Finally, we found that ELL2-R1 (aa 1–353), which carries an RNA polymerase II binding domain, and ELL2-R3 (aa 515–640) are sufficient to interact with Tax-1; however, only ELL2-truncations expressing R1 could enhance Tax-1-mediated transactivation of the HTLV-1 promoter. Together, this study identifies domains in Tax-1 and ELL2 being required for Tax-1:ELL2 complex formation and for viral transactivation.

Introduction VEXAS syndrome, characterized by a UBA1 gene mutation, is a rare and severe systemic inflammatory disease predominantly affecting men. Since its initial description in 2020, it has been noted for its broad clinical phenotype and frequent misdiagnosis. Case Presentation A 76-year-old Caucasian male patient diagnosed with VEXAS syndrome is presented in this case report. He presented with typical symptoms including pulmonary manifestations (infiltrates and effusions), systemic inflammation, and haematological abnormalities. The diagnosis was challenging due to the disease's heterogeneous presentation, often resembling autoimmune or haematological diseases. This patient’s case featured ground-glass opacities and pleural effusions, underlining the significant pulmonary involvement seen in 50–67% of VEXAS patients. His condition was further complicated by recurrent fever and systemic inflammation affecting multiple organs. Conclusion VEXAS syndrome demands an aggressive treatment approach due to its high mortality rate and refractory nature. This case underscores the importance of including VEXAS syndrome in differential diagnoses, particularly for patients with systemic inflammation and pulmonary symptoms, and calls for multidisciplinary management and extensive research to understand its full range of clinical phenotypes. Established facts and novel insights VEXAS syndrome is a rare systemic inflammatory disease with UBA1 gene mutation. VEXAS syndrome involves various UBA 1 gene mutations, including the p.splice c.118-1G > C. It mainly affects men, often misdiagnosed due to its broad clinical phenotype. Novel insights Significant pulmonary involvement in VEXAS, including ground-glass opacities and pleural effusions. Patients with the same mutation exhibit a broad range of disease phenotypes A specific UBA1 mutation as the p.splice c.118-1G > C cannot be directly linked to a distinct disease phenotype Need for aggressive treatment strategies targeting the mutated clone and cytokine storms