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Introduction: This study evaluates the accuracy of iECGs in comparison to the gold standard ECG in adult patients with congenital heart disease and recommends the appropriate iECG derivation based on the patient's characteristics. Methods: In 106 adults (51 female, 55 male) with congenital heart disease, a gold standard 12-lead ECG was recorded, followed by three iECGs with the Apple Watch series 4, which correspond to Einthoven leads I, II, and III. Two experienced and independent cardiologists analyzed the time intervals, amplitudes, and polarities of the ECG parameters as well as the rhythm type and correlated the patient characteristics with the iECG parameters. Results: The iECG parameters of all three iECG leads correlate strongly with those of the gold standard ECG, with exception of the P and T wave durations. We demonstrated that the informative value of the individual iECGs was independent of the patient's characteristics, in particular the heart axis, anatomy, and situs, even if the quality of the Einthoven III-like derivation was partially inadequate. The automatic rhythm analysis of the Apple Watch and the heart rhythm classification of a standard ECG analyzed manually by a cardiologist corresponded in 77%. Conclusion: iECG recordings of adults with congenital heart disease provide comparable results with Einthoven recordings I, II, and III of the 12-lead ECG and current data encourage the use of the Apple Watch not only in patients with structurally normal hearts but also in patients with congenital heart disease.

Abstract Background The aim of our study was to assess the impact the impact of gender and age on reactogenicity to three COVID-19 vaccine products: Biontech/Pfizer (BNT162b2), Moderna (mRNA-1273) and AstraZeneca (ChAdOx). Additional analyses focused on the reduction in working capacity after vaccination and the influence of the time of day when vaccines were administered. Methods We conducted a survey on COVID-19 vaccinations and eventual reactions among 73,000 employees of 89 hospitals of the Helios Group. On May 19th, 2021 all employees received an email, inviting all employees who received at least 1 dose of a COVID-19 to participate using an attached link. Additionally, the invitation was posted in the group’s intranet page. Participation was voluntary and non-traceable. The survey was closed on June 21st, 2021. Results 8375 participants reported on 16,727 vaccinations. Reactogenicity was reported after 74.6% of COVID-19 vaccinations. After 23.0% vaccinations the capacity to work was affected. ChAdOx induced impairing reactogenicity mainly after the prime vaccination (70.5%), while mRNA-1273 led to more pronounced reactions after the second dose (71.6%). Heterologous prime-booster vaccinations with ChAdOx followed by either mRNA-1273 or BNT162b2 were associated with the highest risk for impairment (81.4%). Multivariable analyses identified the factors older age, male gender and vaccine BNT162b as independently associated with lower odds ratio for both, impairing reactogenicity and incapacity to work. In the comparison of vaccine schedules, the heterologous combination ChAdOx + BNT162b or mRNA-1273 was associated with the highest and the homologue prime-booster vaccination with BNT162b with the lowest odds ratios. The time of vaccination had no significant influence. Conclusions Around 75% of the COVID-19 vaccinations led to reactogenicity and nearly 25% of them led to one or more days of work loss. Major risk factors were female gender, younger age and the administration of a vaccine other than BNT162b2. When vaccinating a large part of a workforce against COVID-19, especially in professions with a higher proportion of young and women such as health care, employers and employees must be prepared for a noticeable amount of absenteeism. Assuming vaccine effectiveness to be equivalent across the vaccine combinations, to minimize reactogenicity, employees at risk should receive a homologous prime-booster immunisation with BNT162b2. Trial registration: The study was approved by the Ethic Committee of the Aerztekammer Berlin on May 27th, 2021 (Eth-37/21) and registered in the German Clinical Trials Register (DRKS 00025745). The study was supported by the Helios research grant HCRI-ID 2021-0272.

An environmental proxy routinely used in paleoecological studies of peatlands is testate amoebae, which are used to infer successional and hydrological shifts through time. However, since many species of protists globally remain undescribed, important ecological information about community assemblages and their interaction with environmental conditions in both the past and present has potential gaps. During the analysis of testate amoeba assemblages from peat cores across the Hudson and James Bay region of Canada, a testate amoeba that has not been formally described was discovered with high abundance in subfossil assemblages (up to 50%). We describe this new species, Pyxidicula muskegii sp. nov., using morphometric measurements of tests from these peat core records and demonstrate its environmental preferences using modern samples collected from the same region. The hemispheric shape and irregular areolar surface pattern on the test, along with its preference for lawns in both fens and bogs, support that P. muskegii is a new species. This species is also found in much lower relative abundance in modern samples (<3%) than in paleo-peat core records. This difference in modern and paleo-assemblage suggests that there is a taphonomic bias in their relative abundance with depth, which we attribute to their organic test that is less prone to decomposition. Therefore, it is critical to include rare taxa within future transfer function models to incorporate their environmental tolerances and improve model predictions. [ABSTRACT FROM AUTHOR]

Simple Summary: The treatment of bladder cancer is still a challenge. New treatment options are required for patients not responding to established chemotherapy (e.g., cisplatin) due to primary or acquired chemoresistance. Bladder cancer cells are known for disturbed epigenetics contributing to resistance. This study aimed to investigate the combination of cisplatin, the class I histone deacetylase inhibitor (HDACi) entinostat, and bromodomain inhibitors (BETis) in two urothelial grade 3 bladder carcinoma cell pairs J82, cisplatin-resistant J82 cisR, T24, and cisplatin-resistant T24 LTT. Our results indicate that treatment of bladder cancer cells with entinostat and a BETi prior to cisplatin can completely reverse cisplatin resistance. This is of particular interest since entinostat and OTX015 (one of the used BETi) are already in clinical trials in other cancers. Thus, this study encourages further preclinical and eventually clinical trials with epigenetic inhibitors in combination with cisplatin to re-establish cisplatin efficacy in bladder cancer. Background/Objectives. Cisplatin is part of the first-line treatment of advanced urothelial carcinoma. Cisplatin resistance is a major problem but may be overcome by combination treatments such as targeting epigenetic aberrances. Here, we investigated the effect of the class I HDACi entinostat and bromodomain inhibitors (BETis) on the potency of cisplatin in two pairs of sensitive and cisplatin-resistant bladder cancer cell lines. Cisplatin-resistant J82cisR and T24 LTT were 3.8- and 24-fold more resistant to cisplatin compared to the native cell lines J82 and T24. In addition, a hybrid compound (compound 20) comprising structural features of an HDACi and a BETi was investigated. Results. We found complete (J82cisR) or partial (T24 LTT) reversal of chemoresistance upon combination of entinostat, JQ1, and cisplatin. The same was found for the BETis JQ35 and OTX015, both in clinical trials, and for compound 20. The combinations were highly synergistic (Chou Talalay analysis) and increased caspase-mediated apoptosis accompanied by enhanced expression of p21, Bim, and FOXO1. Notably, the combinations were at least 4-fold less toxic in non-cancer cell lines HBLAK and HEK293. Conclusions. The triple combination of entinostat, a BETi, and cisplatin is highly synergistic, reverses cisplatin resistance, and may thus serve as a novel therapeutic approach for bladder cancer. [ABSTRACT FROM AUTHOR]

It is normally supposed that populations of the same species should evolve shared mechanisms of adaptation to common stressors due to evolutionary constraint. Here, we describe a system of within-species local adaptation to coastal habitats, Brassica fruticulosa, and detail surprising strategic variability in adaptive responses to high salinity. These different adaptive responses in neighboring populations are evidenced by transcriptomes, diverse physiological outputs, and distinct genomic selective landscapes. In response to high salinity Northern Catalonian populations restrict root-to-shoot Na+ transport, favoring K+ uptake. Contrastingly, Central Catalonian populations accumulate Na+ in leaves and compensate for the osmotic imbalance with compatible solutes such as proline. Despite contrasting responses, both metapopulations were salinity tolerant relative to all inland accessions. To characterize the genomic basis of these divergent adaptive strategies in an otherwise non-saline-tolerant species, we generate a long-read-based genome and population sequencing of 18 populations (nine inland, nine coastal) across the B. fruticulosa species range. Results of genomic and transcriptomic approaches support the physiological observations of distinct underlying mechanisms of adaptation to high salinity and reveal potential genetic targets of these two very recently evolved salinity adaptations. We therefore provide a model of within-species salinity adaptation and reveal cryptic variation in neighboring plant populations in the mechanisms of adaptation to an important natural stressor highly relevant to agriculture. [ABSTRACT FROM AUTHOR]

Aims: Heart failure (HF) and chronic kidney disease (CKD) place significant challenges on the healthcare system, and their co‐existence is associated with shared adverse outcomes. The multinational CaReMe project was initiated to provide contemporary, real‐world epidemiological data on cardiovascular and reno‐metabolic diseases. Utilizing data from the German CaReMe cohort, we characterize a multicentric HF population and describe in‐hospital outcomes stratified for co‐morbid CKD. Methods and results: This retrospective, observational study analysed administrative data from inpatient cases hospitalized in 87 German Helios hospitals between 1 January 2016 and 31 August 2022. The first hospitalization of patients aged ≥18 years with a primary discharge diagnosis of HF, based on ICD‐10 codes, were considered the index cases, and subsequent hospitalizations were considered as readmissions. Baseline characteristics and outcomes were stratified for co‐morbid CKD using ICD‐10‐encoding from the index cases. Cox regression was utilized for readmission endpoints and in‐hospital mortality. In total, 174 829 index cases (mean age 79 ± 15 years, 49.9% female) were included; of these, 55.0% had coexisting CKD. Patients with CKD were older, suffered from worse HF‐related symptoms, had a higher co‐morbidity burden, and in‐hospital mortality was increased at index and during follow‐up. Prevalent CKD was associated with higher rehospitalization rates and was an independent predictor for in‐hospital death. Conclusions: Within this HF inpatient cohort from a multicentric German database, CKD was diagnosed in more than half of the patients and was associated with increased in‐hospital mortality at baseline and during follow‐up. Rehospitalizations were observed earlier and more frequently in patients with HF and co‐morbid CKD. [ABSTRACT FROM AUTHOR]

Here we present a new 850-year long coccolithophore record from core SO130-289KL in the northeastern Arabian Sea that spans the Greenland Interstadial 20–Greenland Stadial 20 transition including the timing of the ∼74 ka Youngest Toba Tuff (YTT) supereruption. During the warm interstadial, the coccolithophore assemblage is characterized by Gephyrocapsa oceanica (41%) and Florisphaera profunda (30%) while the succeeding cold stadial is distinguished by the abundance of small placolith species (Emiliania huxleyi + G. ericsonii) (52%). However, the oldest samples of the study interval seem to show a stadial-like coccolithophore assemblage. Spectral analysis revealed an interdecadal cycle imprinted in the coccolithophore record during the interstadial that was also independently reported in other terrestrial and marine proxies. Immediately after the YTT eruption, small placoliths increased by 42% from 5% right below the YTT layer to 47% ∼1 mm above the YTT layer, while G. oceanica and Helicosphaera carteri increased and F. profunda decreased within the ∼1.15 cm layer representing about 8–19 years. Subsequently, the coccolithophore assemblage returned to a composition similar to the warm interstadial period before abruptly changing to a stadial composition characterized by the abundance of small placoliths about 100–130 years after the YTT eruption. Therefore, the YTT eruption had a significant impact on the overall coccolithophore assemblage but appears to have not caused the climate transition from interstadial to stadial conditions, supporting proxy and modeling data. However, the overall mechanism driving the observed changes and cyclicities remains unknown but might be related to rapid atmospheric teleconnections of North Atlantic climate variability to the low latitudes. [ABSTRACT FROM AUTHOR]

The trematodes that cause schistosomiasis in humans require aquatic snails as intermediate hosts. Identifying the genes in snails at which allelic variation controls resistance to infection by schistosomes could lead to novel ways to break the cycle of transmission. We therefore mapped genetic variation within the BS90 population of Biomphalaria glabrata snails that controls their resistance to infection by the SmLE population of Schistosoma mansoni. A marker in the PTC2 genomic region strongly associates with variation in resistance. The S-haplotype, which confers increased susceptibility, appears to be almost completely dominant to the R-haplotype, which confers increased resistance. This result suggests a model in which the parasite must match a molecule on the host side to successfully infect. The genomic region surrounding our marker shows high structural and sequence variability between haplotypes. It is also highly enriched for genes that code for single-pass transmembrane (TM1) genes. Several of the TM1 genes present on the S-haplotype lack orthologs on the R-haplotype, which makes them intriguing candidate genes in a model of dominant susceptibility. These results add to a growing body of work that suggests TM1 genes, especially those in this exceptionally diverse genomic region, may play an important role in snail-schistosome compatibility polymorphisms. Author summary: Schistosomiasis is a parasitic disease of humans that is caused by trematodes in the genus Schistosoma. Schistosomes require aquatic snails as an intermediate host. Infected snails shed parasites into water, which then infect people through their skin. Biomphalaria glabrata host snails show substantial genetic variation for susceptibility to infection by Schistosoma mansoni. Via genome-wide mapping we identified the general location of a gene in the B. glabrata genome at which different alleles control whether snails can be infected or not. The allele that causes susceptibility is dominant to the allele that causes resistance. This uncommon pattern suggests that an invading parasite must match some target on the host side to successfully establish an infection. The mapped snail genomic region contains multiple genes that code for proteins that span cell membranes. These proteins have an extracellular piece that can interact with molecules outside of cells. We hypothesize that these proteins are the targets of molecules produced by the schistosome. If so, then identifying the interacting molecules on the schistosome side, and how they interact with snail proteins, might reveal ways we could genetically modify snails to make them unable to transmit schistosomes to humans. [ABSTRACT FROM AUTHOR]

Background The COVID-19 pandemic has significantly affected acute ischemic stroke (AIS) care. In this study, we examined the effects of the pandemic on neurosurgical AIS care by means of decompressive surgery (DS). Methods In this retrospective observational study, we compared the characteristics, in-hospital processes, and in-hospital mortality rates among patients hospitalized for AIS during the first four waves of the pandemic (between January 1, 2020 and October 26, 2021) versus the corresponding periods in 2019 (prepandemic). We used administrative data from a nationwide hospital network in Germany. Results Of the 177 included AIS cases with DS, 60 were from 2019 and 117 from the first four pandemic waves. Compared with the prepandemic levels, there were no changes in weekly admissions for DS during the pandemic. The same was true for patient age (range: 51.7–60.4 years), the number of female patients (range: 33.3–57.1%), and the prevalence of comorbidity, as measured by the Elixhauser Comorbidity Index (range: 13.2–20.0 points). Also, no alterations were observed in transfer to the intensive care unit (range: 87.0–100%), duration of in-hospital stay (range: 14.6–22.7 days), and in-hospital mortality rates (range: 11.8–55.6%). Conclusion In Germany, compared with the prepandemic levels, AIS patients undergoing DS during the first four waves of the pandemic showed no changes in demographics, rates of comorbidity, and in-hospital mortality rates. This is in contrast to previous evidence on patients with less critical types of AIS not requiring DS and underlines the uniqueness of the subgroup of AIS patients requiring DS. Our findings suggests that these patients, in contrast to AIS patients in general, were unable to forgo hospitalization during the COVID-19 pandemic. Maintaining the delivery of DS is an essential aspect of AIS care during a pandemic. [ABSTRACT FROM AUTHOR]

Das Vorkommen resistenter Ungräser stellt für Landwirte und Beratung ein zusätzliches Problem für die langfristige Planung des Unkrautmanagements dar. Wir stellen hier einen Ansatz zur individuellen Risikoermittlung der Resistenzentwicklung und der Ableitung individueller Maßnahmen zur Resistenzvermeidung und Kontrolle von Ungräsern vor. Die Basis für die Entwicklung eines Beratungs- Algorithmus bildet dabei ein deutschlandweit durchgeführtes Monitoring der Jahre 2019-2021. Auf Basis dieser Daten, zusammen mit weiteren externen Daten, wird mit Hilfe von Verfahren des maschinellen Lernens ein Algorithmus erarbeitet, der frühzeitig auf Resistenz-Probleme einzelner Flächen hinweist und eine Anpassung von Maßnahmen vorschlägt. Ein Prototyp ist für die Saison 2022/23 geplant.

Der Befall und die Resistenzsituation von Alopecurus myosuroides Huds., Apera spica-venti (L.) P. Beauv., Bromus spp. und Lolium spp. wurden in den Jahren 2019-2021 untersucht. Es zeigt sich, dass gerade im Jahr 2021 der Befall höher war als in den Jahren davor. Resistenzen wurden gerade bei A. myosuroides und Lolium spp. sowohl bei den ACCase- als auch bei den ALS-Inhibitoren gefunden, während für Bromus spp. und A. spica-venti eher Probleme bei Sulfonylharnstoffen gefunden wurden. Zunehmend beobachten wir jedoch Fälle von Mischverungrasungen mehrerer resistenter Gräser, die die Landwirte zunehmend vor Probleme stellen.

Abstract Background Circular RNAs (circRNAs) constitute a largely unexplored source for biomarker discovery in prostate cancer (PC). Here, we characterize the biomarker potential of circRNAs in PC, where the need for novel diagnostic and prognostic tools to facilitate more personalized management is pressing. Methods We profiled the transcriptomic landscape of circRNAs in PC by total RNA sequencing of 31 adjacent-normal and 143 tumor samples from localized (radical prostatectomy (RP)) and metastatic PC patients (cohort 1, training). Diagnostic and prognostic potential was evaluated in cohort 1, and 39 top circRNA candidates were selected for validation in two additional PC cohorts (cohort 2, n = 111; RP cohort 3, n = 191) by NanoString-based expression analysis. Biochemical recurrence (BCR)-free survival was assessed using Kaplan-Meier, univariate, and multivariate Cox regression analyses. The circRNA candidates were further detected in extracellular vesicle (EV)-enriched plasma samples from PC patients and controls (cohort 4, n = 54). Results Expression of circABCC4, circFAT3, circATRNL1, and circITGA7 was highly cancer-specific (area under the curve 0.71–0.86), while low circITGA7 expression was significantly (P < 0.05) associated with BCR in univariate analysis in two RP cohorts. Moreover, we successfully trained and validated a novel 5-circRNA prognostic signature (circKMD1A/circTULP4/circZNF532/circSUMF1/circMKLN1) significantly associated with BCR beyond routine clinicopathological variables (RP cohort 1: P = 0.02, hazard ratio = 2.1; RP cohort 3: P < 0.001, hazard ratio = 2.1). Lastly, we provide proof-of-principle for detection of candidate circRNAs in EV-enriched plasma samples from PC patients. Conclusions circRNAs hold great biomarker potential in PC and display both high cancer specificity and association to disease progression.

Abstract Background Whereas the genomic landscape of endocrine‐resistant breast cancer has been intensely characterized in previously treated cases with local or distant recurrence, comparably little is known about genomic alterations conveying primary non‐responsiveness to endocrine treatment in luminal early breast cancer. Methods In this study, 622 estrogen receptor‐expressing breast cancer cases treated with short‐term preoperative endocrine therapy (pET) from the WSG‐ADAPT trial (NCT01779206) were analyzed for genetic alterations associated with impaired endocrine proliferative response (EPR) to 3‐week pET with tamoxifen or aromatase inhibitors. EPR was categorized as optimal (post‐pET Ki67

Mesoscopic (0.1-0.5 mm) interrogation of the living human brain is critical for advancing neuroscience and bridging the resolution gap with animal models. Despite the variety of MRI contrasts measured in recent years at the mesoscopic scale, in vivo quantitative imaging of T2* has not been performed. Here we provide a dataset containing empirical T2* measurements acquired at 0.35 × 0.35 × 0.35 mm3 voxel resolution using 7 Tesla MRI. To demonstrate unique features and high quality of this dataset, we generate flat map visualizations that reveal fine-scale cortical substructures such as layers and vessels, and we report quantitative depth-dependent T2* (as well as R2*) values in primary visual cortex and auditory cortex that are highly consistent across subjects. This dataset is freely available at https://doi.org/10.17605/OSF.IO/N5BJ7, and may prove useful for anatomical investigations of the human brain, as well as for improving our understanding of the basis of the T2*-weighted (f)MRI signal.

Objectives: SARS-CoV-2 rapid antigen tests (RAT) provide fast identification of infectious patients when RT-PCR results are not immediately available. We aimed to develop a prediction model for identification of false negative (FN) RAT results. Methods: In this multicenter trial, patients with documented paired results of RAT and RT-PCR between October 1st 2020 and January 31st 2021 were retrospectively analyzed regarding clinical findings. Variables included demographics, laboratory values and specific symptoms. Three different models were evaluated using Bayesian logistic regression. Results: The initial dataset contained 4,076 patients. Overall sensitivity and specificity of RAT was 62.3% and 97.6%. 2,997 cases with negative RAT results (FN: 120; true negative: 2,877; reference: RT-PCR) underwent further evaluation after removal of cases with missing data. The best-performing model for predicting FN RAT results containing 10 variables yielded an area under the curve of 0.971. Sensitivity, specificity, PPV and NPV for 0.09 as cut-off value (probability for FN RAT) were 0.85, 0.99, 0.7 and 0.99. Conclusion: FN RAT results can be accurately identified through ten routinely available variables. Implementation of a prediction model in addition to RAT testing in clinical care can provide decision guidance for initiating appropriate hygiene measures and therefore helps avoiding nosocomial infections.