Comparison of fludarabine/melphalan (FluMel) with fludarabine/melphalan/BCNU or thiotepa (FBM/FTM) in patients with AML in first complete remission undergoing allogeneic hematopoietic stem cell transplantation – a registry study on behalf of the EBMT Acute Leukemia Working Party

\ua9 2023, The Author(s).Conditioning protocols for patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT) are being developed continuously to improve their anti-leukemic efficacy and reduce their toxicity. In this study, we compared the conditioning protocol of fludarabine with melphalan 140 mg/m2 (FluMel) with conditioning protocols based on this same backbone but with an additional alkylating agent i.e., either fludarabine/BCNU (also known as carmustine)/melphalan (FBM), or fludarabine/thiotepa/melphalan (FTM) 110 mg/m2. We included 1272 adult patients (FluMel, n = 1002; FBM/FTM, n = 270) with acute myeloid leukemia (AML) with intermediate/poor cytogenetic risk in first complete remission (CR) from the registry of the EBMT Acute Leukemia Working Party. Despite patients in the FBM/FTM group were older (64.1 years vs. 59.8 years, p < 0.001) and had a worse Karnofsky performance score (KPS < 90, 33% vs. 24%, p = 0.003), they showed a better overall survival (OS) (2 y OS: 68.3% vs. 58.1%, p = 0.02) and less non-relapse mortality (NRM) (2 y NRM: 15.8% vs. 22.2%, p = 0.009) compared to patients treated with FluMel. No significant differences were observed in relapse incidence (RI) (2 y RI: 24.9% vs. 23.7%, p = 0.62). In conclusion, the addition of a second alkylating agent (BCNU/carmustine or thiotepa) to FluMel as FBM/FTM conditioning, improves OS in AML patients in first CR with intermediate/poor risk cytogenetics after allo-HCT

The diagnostic suitability of a xerostomia questionnaire and the association between xerostomia, hyposalivation and medication use in a group of nursing home residents

The study objective was to explore the diagnostic suitability of the Xerostomia Inventory and the association between xerostomia, hyposalivation and medication use in a group of nursing home residents. A cross-sectional study was carried out in 50 physically impaired nursing home residents (20 men) with a mean age of 78.1 years (range, 53–98) in The Netherlands. The Xerostomia Inventory-Dutch version was completed for all residents and the data were subjected to exploratory factor analysis to determine the diagnostic suitability. Residents’ data on xerostomia, whole saliva secretion rates and hyposalivation-related medications used were collected and statistically analyzed. The diagnostic suitability of the Xerostomia Inventory-Dutch version appeared restricted. The prevalence of xerostomia was 52%, without gender and age difference. The prevalence of hyposalivation was 24% for resting, 60% for chewing-stimulated and 18% for acid-stimulated whole saliva. All whole saliva secretion rates were significantly lower in women than in men and in older than in younger residents. Forty-four percent of all medications used were hyposalivation-related and women used significantly more medications than men. Xerostomia was significantly negatively correlated with the resting whole saliva secretion rate. The number of hyposalivation-related medications used was not significantly correlated with the various whole saliva secretion rates. In nursing home residents, xerostomia, hyposalivation and using hyposalivation-related medications seem common and partially associated features

Roles of glial cells in synapse development

Brain function relies on communication among neurons via highly specialized contacts, the synapses, and synaptic dysfunction lies at the heart of age-, disease-, and injury-induced defects of the nervous system. For these reasons, the formation—and repair—of synaptic connections is a major focus of neuroscience research. In this review, I summarize recent evidence that synapse development is not a cell-autonomous process and that its distinct phases depend on assistance from the so-called glial cells. The results supporting this view concern synapses in the central nervous system as well as neuromuscular junctions and originate from experimental models ranging from cell cultures to living flies, worms, and mice. Peeking at the future, I will highlight recent technical advances that are likely to revolutionize our views on synapse–glia interactions in the developing, adult and diseased brain

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency–Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research

Revised diagnosis and severity criteria for sinusoidal obstruction syndrome/veno-occlusive disease in adult patients : a new classification from the European Society for Blood and Marrow Transplantation

Sinusoidal obstruction syndrome, also known as veno-occlusive disease (SOS/VOD), is a potentially life threatening complication that can develop after hematopoietic cell transplantation. Although SOS/VOD progressively resolves within a few weeks in most patients, the most severe forms result in multi-organ dysfunction and are associated with a high mortality rate (480%). Therefore, careful attention must be paid to allow an early detection of SOS/VOD, particularly as drugs have now proven to be effective and licensed for its treatment. Unfortunately, current criteria lack sensitivity and specificity, making early identification and severity assessment of SOS/VOD difficult. The aim of this work is to propose a new definition for diagnosis, and a severity-grading system for SOS/VOD in adult patients, on behalf of the European Society for Blood and Marrow Transplantation.Peer reviewe

Chronological studies of the Arzhan-2 Scythian monument in Tuva (Russia)

The first radiocarbon dates from the unique early Scythian monument Arzhan-2, discovered in 2001, are presented. The monument contained a royal burial (grave nr 5). Unfortunately, precise dating is hampered by the Hallstatt plateau in the calibration curve. However, using both accelerator mass spectrometry measurements from buried materials and conventional dates for floating tree rings from the burial chamber, we were able to date the construction of the monument to the 7th century BC. This is consistent with archaeological expectations. Other graves located inside the barrow were also dated. Grave nr 11, located on the edge of the barrow, is younger, showing that the monument was a place of burial ritual for many years for this ancient population.