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HOXA9 and MEIS1 are frequently upregulated in acute myeloid leukemia (AML), including those with MLL‐rearrangement. Because of their pivotal role in hemostasis, HOXA9 and MEIS1 appear non‐druggable. We, thus, interrogated gene expression data of pre‐leukemic (overexpressing Hoxa9) and leukemogenic (overexpressing Hoxa9 and Meis1; H9M) murine cell lines to identify cancer vulnerabilities. Through gene expression analysis and gene set enrichment analyses, we compiled a list of 15 candidates for functional validation. Using a novel lentiviral multiplexing approach, we selected and tested highly active sgRNAs to knockout candidate genes by CRISPR/Cas9, and subsequently identified a H9M cell growth dependency on the cytosolic phospholipase A2 (PLA2G4A). Similar results were obtained by shRNA‐mediated suppression of Pla2g4a. Remarkably, pharmacologic inhibition of PLA2G4A with arachidonyl trifluoromethyl ketone (AACOCF3) accelerated the loss of H9M cells in bulk cultures. Additionally, AACOCF3 treatment of H9M cells reduced colony numbers and colony sizes in methylcellulose. Moreover, AACOCF3 was highly active in human AML with MLL rearrangement, in which PLA2G4A was significantly higher expressed than in AML patients without MLL rearrangement, and is sufficient as an independent prognostic marker. Our work, thus, identifies PLA2G4A as a prognostic marker and potential therapeutic target for H9M‐dependent AML with MLL‐rearrangement.
In den Frühen Hilfen und im Kinderschutz fehlen selektive und indizierte Präventionsmaßnahmen für Väter mit einem hohen Risiko für (wiederholte) Kindesmisshandlung. Das kanadische Caring Dads Programm wird seit 2008 in Deutschland eingesetzt. Ziel dieser Studie war es, Väter zu untersuchen, die bis 2016 an einem Caring Dads Programm in Düsseldorf, Hannover oder Groß-Gerau teilgenommen haben. Die Studie an n = 60 Vätern und n = 34 Müttern beinhaltete die Veränderungsmessung von selbstberichteter Aggressivität, Erziehungsverhalten und Co-Parenting der Väter sowie Lebensqualität und Co-Parenting der Mütter, den Vergleich von in Deutschland und Kanada teilnehmenden Vätern (n = 59/64) und eine postalische Katamnese (n = 20). Die Ergebnisse zeigen im Mittel Verbesserungen von väterlicher Aggressivität (d = .39) und Erziehungsverhalten (d = .80, normiert: φ = .46) sowie mütterlichem Co-Parenting (d = .46) und väterlichem Verhalten gegenüber der Partnerin aus Müttersicht (d = .47). Bei einem Viertel bis einem Drittel risikobelasteter Väter waren die Verbesserungen bei Kontrolle von Messfehlern mittels Reliable Change Index klinisch signifikant. Deutsche Väter berichteten eine höhere Änderungssensitivität (T1/T2: d = 1.37/1.59) und verbale Aggressivität (T1/T2: d = 1.29/1.36) verglichen mit kanadischen Vätern. Die Katamnese zeigt subjektiv bedeutsame Verbesserungen der Beziehungs- und Erziehungsqualität aus Vätersicht. Die Evaluation liefert keine Hinweise auf kulturbedingte Hürden bei der Implementierung von Caring Dads in Deutschland.
We present a small case study on citations of conference posters using poster collections from both Figshare and Zenodo. The study takes into account the years 2016–2020 according to the dates of publication on the platforms. Citation data was taken from DataCite, Crossref and Dimensions. Primarily, we want to know to what extent scientific posters are being cited and thereby which impact posters potentially have on the scholarly landscape and especially on academic publications. Our data-driven analysis reveals that posters are rarely cited. Citations could only be found for 1% of the posters in our dataset. A limitation in this study however is that the impact of academic posters was not measured empirical but rather descriptive.
The objective of this study was to investigate the occurrence of bacteremia in dairy cows with severe mastitis. Milk samples were collected from affected udder quarters, and corresponding blood samples were collected from dairy cows with severe mastitis at the time of diagnosis before any therapeutic measures were undertaken. The cultural detection of pathogens in blood classified a bacteremia. Further diagnostic tests were performed to provide evidence of bacteremia. This was realized by PCR with regard to S. aureus, E. coli and S. uberis and the Limulus test. Detection of culturable pathogens in the blood of cows with severe clinical mastitis was rare and occurred in only one of 70 (1.4%) cases. Overall, bacterial growth was detected in 53 of 70 (75.7%) milk samples. S. uberis (22/70), E. coli (12/70) and S. aureus (4/70) were the most frequently isolated pathogens from milk of cows with severe mastitis. PCR was performed in 38 of 70 (54.3%) blood samples. PCR was positive in eight of 38 cases. S. uberis was found most frequently in six blood samples (8.6%). E. coli was found on PCR in one blood sample (1.4%). S. aureus was identified in one blood sample (1.4%). When Coliforms were detected in the quarter milk sample, a Limulus test was performed in the corresponding blood sample. In three of 15 cases, the Limulus test was positive (4.3% of samples). Further studies are needed to investigate the occurrence of bacteremia in cows with severe mastitis in a higher population size.
Since child maltreatment has highly negative effects on child adjustment, early identification of at-risk families is important. This study focuses on longitudinal risk factors for child maltreatment and associations between abuse risk and occurrence. It also examines whether abuse risk and involvement in early childhood intervention are associated. The sample comprises 197 German caregivers with children under 3 years of age. Data was collected in two waves. The Brief Child Abuse Potential Inventory assessed abuse risk. Socio-demographic, parent, child and family-related risk factors were measured using screening tools. The analysis revealed that parental characteristics (psychopathology, own maltreatment experiences etc.) were associated with concurrent abuse risk. Longitudinal changes in abuse risk were linked to caregiver education and child-related factors. Cumulative risk did not explain more variance than specific risk factors. Significant associations with caregiverreported abuse were found, and data suggest that some burdened families cannot be reached by early childhood intervention.
Introduction: Renal cell carcinoma (RCC), an immunogenic tumor, is the most common form of kidney cancer worldwide. Immune checkpoint inhibitors (ICIs) play an important role in the treatment of metastatic RCC. Programmed death-ligand (PD-L1) has already been proposed as a possible prognosticator for ICIs effectiveness. To elucidate the feasible role of ICIs in neoadjuvant settings, we have assessed the most common PD-L1 expression modalities [tumor proportion score (TPS), combined positivity score (CPS) and inflammatory cell (IC) score] in primary tumors (PTs) and venous tumor thrombi (VTT) in first diagnosed, previously untreated RCC patients with accompanying
VTT.
Methods: Between January 1999 and December 2016, 71 patients with a first diagnosed, untreated, locally advanced RCC (aRCC) (≥ pT3a) underwent surgery in Hanover Medical School (MHH). PD-L1 expression was examined separately in PTs and VTT using the CPS, IC score and TPS. We also considered the age at the time of the initial surgery and gender as probable influencing factors. By using a cutoff value of 1 (1%), PD-L1 expression levels in PTs and VTT were assessed to enable the determination of any frequency differences.
Results: Positive scores for PTs were shown by 54 (CPS), 53 (IC score) and 34 (TPS) patients, whereas in VTT, positive scores were evaluated
for a total of 50 (CPS), 47 (IC-score) and 36 (TPS) patients. No statistically significant differences were obtained between the PD-L1 expression immunoscores for PTs and VTT. The covariates age at the time of the initial surgery and gender could not be statistically proven to influence the differences in PD-L1 expression between the
VTT and PTs.
Conclusion: To the best of our knowledge, this research is the largest study to investigate PD-L1 expression in PTs and VTT in 71 cases. It could have relevance for the future development of neoadjuvant immunotherapy options, particularly in aRCC with VTT.
Cora Baltussen in den USA : Lernerfahrungen für die Supervision in den Niederlanden und Deutschland
(2021)
Cora Baltussen unternahm - wie zahlreiche europäische Sozialarbeitende - Anfang der 1950er Jahre eine 18-monatige Studienreise in die USA, um Casework und Supervision zu erlernen. Dieser Beitrag wertet ihren Summerreport von 1953 aus, der als Archivalie erhalten ist. So können ihre Lernerfahrungen in der historisch-kritischen Rekonstruktion kontextualisiert und in den Diskurs eingeordnet werden. Dabei werden erste Differenzierungen der frühen Supervisionsgeschichte ebenso sichtbar wie prägende Begegnungen und entstehende Netzwerke, die die Supervisionsentwicklung in Deutschland maßgeblich beeinflussten.
In this species differentiation study of Corynebacterium spp. (C. spp.), quarter foremilk samples from 48 farms were included. These were obtained from both clinically healthy cows and those with clinical mastitis. First, all samples were examined cyto-microbiologically and all catalase-positive rods were differentiated using the direct transfer method in MALDI-TOF MS. C. bovis, C. amycolatum, C. xerosis, and five other species were identified with proportions of 90.1%, 7.7%, and 0.8% for the named species, respectively, and 1.4% for the remaining unnamed species. In addition, somatic cell count (SCC) was determined by flow cytometry. Based on this, the isolates were classified into four udder health groups: “latent infection”, “subclinical mastitis”, “clinical mastitis” and “others”. Approximately 90% of isolates of C. bovis and C. amycolatum were from latently and subclinically infected quarters. Of the C. bovis isolates, 5.8% were obtained from milk samples from clinical mastitis, whereas C. amycolatum was not present in clinical mastitis. The distribution of groups in these two species differed significantly. The geometric mean SCC of all species combined was 76,000 SCC/mL, almost the same as the SCC of C. bovis. With 50,000 SCC/mL, the SCC of C. amycolatum was slightly below the SCC of C. bovis. Through the species-level detection and consideration of SCC performed here, it is apparent that individual species differ in terms of their pathogenicity. Overall, their classification as minor pathogens with an SCC increase is confirmed.
The aim of this study was to define the time-related period of intramammary infections and its relation to risk factors for intramammary infections and clinical mastitis at cow and quarter levels. In total, 269 German Holstein Frisian dairy cows on three farms in Northern and Eastern Germany were included in this study. Quarter milk samples were collected at dry-off, 3 ± 1 days after calving and 17 ± 3 days after calving, for cytomicrobiological examination. Risk factors at quarter- and cow-level associated with intramammary infections and clinical mastitis were recorded during the trial period. Data were analyzed using logistic regression procedures and odds ratios were calculated. Calving for the second time increased the odds of clinical mastitis during the first 100 days of lactation compared to cows calving for the third time or more. A high milk yield after calving was a risk factor for new infections, with environmental pathogens 17 ± 3 days postpartum. A body condition score after calving less than 3.5 was associated with a decreased risk of having an intra-mammary infection (IMI) with non-aureus staphylococci and coryneforms 3 ± 1 days postpartum and consistent body condition between dry-off and early lactation decreased the risk of intramammary infections after calving. The absence of a ring of hyperkeratosis at the teat apex shown at dry-off was associated with a lower risk of intramammary infections with environmental pathogens 17 ± 3 days postpartum. This study shows the important influence of the dry period and early lactation on intramammary infections and clinical mastitis postpartum in dairy cows. Udder quarters may have eliminated pathogens during the dry period in 43.6% of cases in this study. Additionally, new infections occurred during early lactation, so 5.1% more quarters were infected 17 ± 3 days compared to 3 ± 1 days postpartum. New infections can be traced to non-aureus staphylococci and Staphylococcus aureus from dry-off up until 3 ± 1 days postpartum, and to non-aureus staphylococci, Staphylococcus aureus and Streptococcus uberis, after calving. In total, 88.7% of the infected quarters showed new infections with another pathogen species 3 ± 1 days postpartum than at dry-off, and 89.2% of the quarters 17 ± 3 days postpartum than 3 ± 1 days postpartum. In conclusion, the early lactation has just as important an influence on intramammary infections postpartum in dairy cows as the dry period. There is the possibility that udder quarters eliminate pathogens during the early lactation, especially during the dry period. However, there is also the danger that new infections manifest, with a large proportion of new infections occurring after calving. Thus, additional control strategies are of great importance to prevent new infections occurring during early lactation as well as during the dry period to reduce negative effects on milk yield and culling hazards in dairy cows by minimizing the associated risk factors
Lack of knowledge regarding antibiotics use has been widely identified as a main reason for inappropriate antibiotics use which leads to antibiotic resistance phenomenon. This study aimed to evaluate the effects of pharmacist-initiated educational intervention on promoting appropriate use of antibiotics and reducing self-medication with antibiotics. A pre and post intervention study using two validated self-administered questionnaires was performed in Yogyakarta province. A-two hour session of course and case discussion was delivered as method of intervention. Pharmacy customers attended Gema Cermat program were invited conveniently to complete both of pre- and post-educational questionnaires. Descriptive presentation was conducted to show scores on questions. Knowledge scores were categorized as poor, adequate and high. Of 268 respondents, 34.22% respondents had poor level of knowledge before receiving educational intervention, but this number decreased into 12.21% after post-interventional phase. Another 28.23% respondents had adequate level of knowledge before and then elevated into 38.28% after receiving education about appropriate use of antibiotics. Pre-education, 37.43% participants had a high level of knowledge about antibiotics use and resistance, whereas after education the number became slightly higher (49.25%). A vast majority of respondents (75.24%) became more aware about appropriate antibiotics practice after receiving educational inter- vention. Overall, didactic educational intervention imposed higher knowledge and better practice regarding antibiotics use (p < 0.05). This study showed that using didactical education intervention towards antibiotics use and resistance can be an initial strategy that led to substantial improvement of appropriate antibiotics use. Further systemic interventions to educate people should be performed and evaluated in order to promote the appropriate use of antibiotics.