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Both agronomic practices and spatial position can determine the assemblage of herbaceous species. We assess the dynamics and the contribution of these two aspects over time to the herb assemblages of different cocoa production systems. Braun-Blanquet surveys were performed over seven years in a long-term trial in Bolivia to compare different cocoa production systems: successional agroforestry (SA) with no external inputs, organic agroforestry (OA) and organic monoculture (OM), both including a leguminous perennial cover crop, conventional agroforestry (CA) and conventional monoculture (CM), where agrochemicals were applied. Using general linear models and multivariate analysis we found that assemblages were mainly driven by spatial position only at the beginning. After this, a very dynamic selection process related to the different management practices took place, which became more stable over the years. We observed a decline in species in both the CA and OA systems, due to the loss of heliophilous species and the low number of new species established in them. The OM presented the most conservative pattern, with the lowest number of new species and species lost, due to the presence of the cover crop. Both the most intensively managed system (CM) and the most diverse and least intensive one (SA) had the highest number of new species recorded over time, which led to highly specialized assemblages, with worldwide distributed and herbicide resistant species in the first case and secondary forest species, in the second. We conclude that the promotion of organic management and agroforestry systems, especially highly divers and successional agroforestry sytems would favour herb assemblages with high conservation value and prevent the establishment of globally distributed species.

Pathogenic and relative fitness of thiabendazole (TBZ)-resistant and TBZ-sensitive isolates of Penicillium digitatum was compared on oranges. No differences could be found amongst the parameters used to measure pathogenic fitness (i.e., decay incidence, lesion expansion rate, latent period and sporulation intensity). Relative fitness was determined in competition experiments pairing resistant and sensitive isolates. Resistant isolates proved to be less fit. Die absolute und relative Fitneß für Thiabendazol resistente und sensitive Stämme von Penicillium digitatum wurde auf Orangen verglichen. Es konnten zwischen den für die absolute Fitneß gemessenen Parametern (Befallshäufigkeit Fäule, Wachstumsrate der Läsionen und Sporulationsintensität) keine Unterschiede festgestellt werden. Die relative Fitneß wurde in Konkurrenzversuchen mit resistenten und sensitiven Isolaten untersucht. Resistente Isolate erwiesen sich als weniger fit.

TREC-NBS identifies patients with inborn errors of immunity (IEI) and syndromic features, but uncertainty remains regarding their immunological management. To address this, syndromic patients detected by TREC-NBS in Germany between August 2019 and April 2024 were systematically analyzed, including phenotype, treatment, and outcomes. National registries were screened, and data were completed by the treating centres. A total of 77 syndromic patients were identified, with 22 different gene defects found in 72 individuals (93.5%). Primary thymic deficiency was present in 64% (49/77), most commonly due to 22q11.2 deletion syndrome (62%). Common clinical features included congenital heart disease (57%), facial/skeletal abnormalities (53%), and neurological symptoms (36%). Definitive treatments were provided promptly in eligible patients, including 6 thymus transplants and 6 hematopoietic stem cell transplants (HSCT). A watch-and-wait approach was applied to the remaining patients, with 34% (22/65) receiving prophylactic treatment. Recovery of CD3 + T-cell counts was limited to a minority. Overall survival was 89%, with a median follow-up of 32 months (range 0.5–60). To conclude, this is the first comprehensive study of syndromic IEI patients identified through TREC-NBS. The findings show that the German healthcare system enables both early prophylactic care and timely access to definitive therapies. Moving forward, interdisciplinary collaboration will be key to developing evidence-based management guidelines for this challenging patient group.

Recently, chemical blood parameters gain more attraction as potential prognostic parameters in pancreatic cancer (PC). In the present study we investigated the prognostic relevance of the uric acid (UA) level in blood plasma at the time of diagnosis for overall survival (OS) in a large cohort of patients with PC. Data from 466 consecutive patients with ductal adenocarcinoma of the pancreas were evaluated retrospectively. Overall survival (OS) was analysed using the Kaplan-Meier method. To further evaluate the prognostic significance of the UA level, univariate and multivariate Cox regression models were calculated. None of the clinicopathological parameters (tumour grade, clinical stage, age, CA19-9 level, Karnofski Index (KI) or surgical resection) except gender was associated with UA level. In univariate analysis we observed the elevated UA level (<5.1 versus ≥5.1 mg/dl, p = 0.017) as poor prognostic factor for OS. In the multivariate analysis that included age, gender, tumour grade, tumour stage, surgical resection, CA19-9 level, the KI and UA level we confirmed the UA level as independent prognostic factor for OS (HR = 1.373%; CI = 1.077-1.751; p = 0.011). In conclusion, we identified the UA level at time of diagnosis as an independent prognostic factor in PC patients. Our results indicate that the UA level might represent a novel and useful marker for patient stratification in PC management.

Model systems that mimic human cardiac structure and function are essential for the development of novel diagnostics and effective treatments for cardiovascular diseases. While non‐human vertebrate models, from zebrafish to pig, remain vital to cardiovascular research, the translatability of findings to human patients is often limited. Therefore, animal experiments should be supplemented with human model systems, including human induced pluripotent stem cell‐derived cells, 3D engineered constructs, and last but not least, native tissue preparations and isolated primary cardiomyocytes. However, while human myocardium remains the gold standard, human heart tissue – and particularly tissue from control hearts–remains scarce, and its use in research is generally restricted to settings where tissue has been excised from diseased or failing hearts. While it is in principle possible to use tissue from rejected non‐failing donor hearts that cannot be transplanted, legal hurdles (e.g., in Germany) can restrict the use of non‐transplanted donor organs in research. Given the challenges associated with accessing and using human tissue in biomedical research, an integrated strategy towards combining non‐human vertebrate models, in silico models, and human tissue‐derived models is recommended, enhancing the chances of successful research and development, and helping bridge the gap between preclinical and clinical research. This manuscript reviews models that can be used to study the physiology and pathophysiology of the heart, and describes some the limitaions and ethical concerns associated with the use of human tissue.

Intrauterine exposure to zidovudine-based combination antiretroviral therapy (cART) can cause severe anemia within the first weeks of life. Tenofovir disoproxil fumarate (TDF)–based regimens may have less hematologic side effects but may affect growth parameters. This study aimed to assess the safety of TDF for prevention of mother-to-child transmission (PMTCT) in HIV-exposed uninfected infants regarding early growth outcomes and hematologic side effects. Our retrospective observational cohort study included children born (n = 232) to HIV-infected mothers (n = 228) on cART. Blood counts were compared at birth, 4–6 weeks, and 3, 12 and 18 months of age. Growth parameters were measured at birth and 12 and 18 months of age. Data were analyzed according to treatment group (TDF and non-TDF cART regimes). The median hemoglobin (Hgb) was significantly lower in the non-TDF-based group at birth (15.4 g/dl vs. 16.9 g/dl; **p = 0.002) and at 4–6 weeks of age (9.9 g/dl vs. 10.4 g/dl; **p = 0.004). The mean corpuscular volume was higher in the non-TDF-based group (109 fl vs. 105 fl; ***p < 0.001) as well at 4–6 weeks (102 fl vs. 95 fl; ***p < 0.001). In the TDF-based group, a higher proportion of neutropenia (grade 2 and higher) compared to the non-TDF-group (21.4% vs. 11%; *p = 0.015) was observed at three months of age. This effect was transient. There was no difference in growth.Conclusions: TDF appears to have no major side effects in our cohort. Transient anemia was observed more commonly with non-TDF regimens. However, our research suggests a potential delayed effect of TDF on neutrophils at 3 months of age.What is Known:• TDF is suspected to affect the growth of HIV-exposed uninfected infants.• Non-TDF-based cART regimes for prevention of mother-to-child transmission of HIV often result in transient anemia in the infant.What is New:• TDF appears to have no major side effects regarding the growth of HIV-exposed uninfected infants.• Our research suggests a potential delayed effect of TDF on neutrophils at 3 months of age in these infants.

Background: Due to the increase in survival rates for congenital heart disease (CHD) in the last decades, over 90% of patients today reach adulthood. Currently, there are more than 300,000 adults with CHD (ACHD) living in Germany. They have an increased need for specialized medical care, since almost all ACHD have chronic heart disease and suffer from specific chronic symptoms, risks, and sequelae. Primary care physicians (PCPs) play a crucial role in referring patients to ACHD specialists or specialized institutions. This cross-sectional study is intended to clarify the real-world care of ACHD from the PCP’s perspective. Methods: This analysis, initiated by the German Heart Centre Munich, was based on a 27-item questionnaire on actual ACHD health care practice in Germany from the PCP’s perspective. Results: In total, 767 questionnaires were considered valid for inclusion. The majority of the PCPs were general practitioners (95.9%), and 84.1% had cared for ACHD during the past year. A majority (69.2%) of the PCPs had cared for patients with simple CHD, while 50.6% and 33.4% had cared for patients with moderate and severe CHD, respectively, in all age groups. PCPs treated almost all typical residual symptoms and sequelae, and advised patients regarding difficult questions, including exercise capacity, pregnancy, genetics, and insurance matters. However, 33.8% of the PCPs did not even know about the existence of certified ACHD specialists or centers. Only 23.9% involved an ACHD-specialized physician in their treatment. In cases of severe cardiac issues, 70.8% of the PCPs referred patients to ACHD-certified centers. Although 52.5% of the PCPs were not sufficiently informed about existing structures, 64.2% rated the current care situation as either “very good” or “good”. Only 26.3% (n = 190) of the responding physicians were aware of patient organizations for ACHD. Conclusions: The present study showed that the majority of PCPs are not informed about the ACHD care structures available in Germany. The need for specialized ACHD follow-up care is largely underestimated, with an urgent need for optimization to reduce morbidity and mortality. For the future, solutions must be developed to integrate PCPs more intensively into the ACHD care network.