Comparison of netupitant/palonosetron with 5-hydroxytryptamine-3 receptor antagonist in preventing of chemotherapy-induced nausea and vomiting in patients undergoing hematopoietic stem cell transplantation

BackgroundThe use of 5-hydroxytryptamine-3 receptor antagonists (5HT3RA) has long been considered the standard regimen for preventing chemotherapy-induced nausea and vomiting (CINV) prior to hematopoietic stem cell transplantation (HSCT). However, their therapeutic outcomes have been unsatisfactory. NEPA, an oral formulation combining the neurokinin-1 receptor antagonist netupitant and the 5HT3RA palonosetron, has received regulatory approval for the management of highly and moderately emetogenic chemotherapy. This study aims to compare the efficacy of NEPA with that of 5HT3RA alone in preventing CINV among patients undergoing multiday conditioning chemotherapy prior to HSCT.Patients and methodsWe conducted a retrospective analysis of patients who underwent HSCT between September 2019 and September 2022. Efficacy outcomes were assessed based on the rates of patients achieving complete response (CR: no emesis and no use of rescue medication), complete control (CC: CR without significant nausea), no vomiting, and no significant nausea.ResultsThe NEPA group consisted of 106 patients, while the 5HT3RA group included 107 patients. The NEPA group exhibited significantly higher rates of CR compared to the 5HT3RA group during the overall phase (71.7% vs. 32.7%, P<0.001), acute phase (78.3% vs. 43.0%, P<0.001), and delayed phase (84.9% vs. 58.9%, P<0.001). Similarly, rates of CC, no vomiting, and no significant nausea were significantly better in the NEPA group across all phases (P<0.001).ConclusionNEPA demonstrated superior efficacy compared to 5HT3RA in preventing CINV during all phases of multiday conditioning regimens among patients undergoing HSCT

Off-line evaluation of indoor positioning systems in different scenarios: the experiences from IPIN 2020 competition

Every year, for ten years now, the IPIN competition has aimed at evaluating real-world indoor localisation systems by testing them in a realistic environment, with realistic movement, using the EvAAL framework. The competition provided a unique overview of the state-of-the-art of systems, technologies, and methods for indoor positioning and navigation purposes. Through fair comparison of the performance achieved by each system, the competition was able to identify the most promising approaches and to pinpoint the most critical working conditions. In 2020, the competition included 5 diverse off-site off-site Tracks, each resembling real use cases and challenges for indoor positioning. The results in terms of participation and accuracy of the proposed systems have been encouraging. The best performing competitors obtained a third quartile of error of 1 m for the Smartphone Track and 0.5 m for the Foot-mounted IMU Track. While not running on physical systems, but only as algorithms, these results represent impressive achievements.Track 3 organizers were supported by the European Union’s Horizon 2020 Research and Innovation programme under the Marie Skłodowska Curie Grant 813278 (A-WEAR: A network for dynamic WEarable Applications with pRivacy constraints), MICROCEBUS (MICINN, ref. RTI2018-095168-B-C55, MCIU/AEI/FEDER UE), INSIGNIA (MICINN ref. PTQ2018-009981), and REPNIN+ (MICINN, ref. TEC2017-90808-REDT). We would like to thanks the UJI’s Library managers and employees for their support while collecting the required datasets for Track 3. Track 5 organizers were supported by JST-OPERA Program, Japan, under Grant JPMJOP1612. Track 7 organizers were supported by the Bavarian Ministry for Economic Affairs, Infrastructure, Transport and Technology through the Center for Analytics-Data-Applications (ADA-Center) within the framework of “BAYERN DIGITAL II. ” Team UMinho (Track 3) was supported by FCT—Fundação para a Ciência e Tecnologia within the R&D Units Project Scope under Grant UIDB/00319/2020, and the Ph.D. Fellowship under Grant PD/BD/137401/2018. Team YAI (Track 3) was supported by the Ministry of Science and Technology (MOST) of Taiwan under Grant MOST 109-2221-E-197-026. Team Indora (Track 3) was supported in part by the Slovak Grant Agency, Ministry of Education and Academy of Science, Slovakia, under Grant 1/0177/21, and in part by the Slovak Research and Development Agency under Contract APVV-15-0091. Team TJU (Track 3) was supported in part by the National Natural Science Foundation of China under Grant 61771338 and in part by the Tianjin Research Funding under Grant 18ZXRHSY00190. Team Next-Newbie Reckoners (Track 3) were supported by the Singapore Government through the Industry Alignment Fund—Industry Collaboration Projects Grant. This research was conducted at Singtel Cognitive and Artificial Intelligence Lab for Enterprises (SCALE@NTU), which is a collaboration between Singapore Telecommunications Limited (Singtel) and Nanyang Technological University (NTU). Team KawaguchiLab (Track 5) was supported by JSPS KAKENHI under Grant JP17H01762. Team WHU&AutoNavi (Track 6) was supported by the National Key Research and Development Program of China under Grant 2016YFB0502202. Team YAI (Tracks 6 and 7) was supported by the Ministry of Science and Technology (MOST) of Taiwan under Grant MOST 110-2634-F-155-001

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Off-Line Evaluation of Indoor Positioning Systems in Different Scenarios: The Experiences From IPIN 2020 Competition

Every year, for ten years now, the IPIN competition has aimed at evaluating real-world indoor localisation systems by testing them in a realistic environment, with realistic movement, using the EvAAL framework. The competition provided a unique overview of the state-of-the-art of systems, technologies, and methods for indoor positioning and navigation purposes. Through fair comparison of the performance achieved by each system, the competition was able to identify the most promising approaches and to pinpoint the most critical working conditions. In 2020, the competition included 5 diverse off-site off-site Tracks, each resembling real use cases and challenges for indoor positioning. The results in terms of participation and accuracy of the proposed systems have been encouraging. The best performing competitors obtained a third quartile of error of 1 m for the Smartphone Track and 0.5 m for the Foot-mounted IMU Track. While not running on physical systems, but only as algorithms, these results represent impressive achievements.Track 3 organizers were supported by the European Union’s Horizon 2020 Research and Innovation programme under the Marie Skłodowska Curie Grant 813278 (A-WEAR: A network for dynamic WEarable Applications with pRivacy constraints), MICROCEBUS (MICINN, ref. RTI2018-095168-B-C55, MCIU/AEI/FEDER UE), INSIGNIA (MICINN ref. PTQ2018-009981), and REPNIN+ (MICINN, ref. TEC2017-90808-REDT). We would like to thanks the UJI’s Library managers and employees for their support while collecting the required datasets for Track 3. Track 5 organizers were supported by JST-OPERA Program, Japan, under Grant JPMJOP1612. Track 7 organizers were supported by the Bavarian Ministry for Economic Affairs, Infrastructure, Transport and Technology through the Center for Analytics-Data-Applications (ADA-Center) within the framework of “BAYERN DIGITAL II. ” Team UMinho (Track 3) was supported by FCT—Fundação para a Ciência e Tecnologia within the R&D Units Project Scope under Grant UIDB/00319/2020, and the Ph.D. Fellowship under Grant PD/BD/137401/2018. Team YAI (Track 3) was supported by the Ministry of Science and Technology (MOST) of Taiwan under Grant MOST 109-2221-E-197-026. Team Indora (Track 3) was supported in part by the Slovak Grant Agency, Ministry of Education and Academy of Science, Slovakia, under Grant 1/0177/21, and in part by the Slovak Research and Development Agency under Contract APVV-15-0091. Team TJU (Track 3) was supported in part by the National Natural Science Foundation of China under Grant 61771338 and in part by the Tianjin Research Funding under Grant 18ZXRHSY00190. Team Next-Newbie Reckoners (Track 3) were supported by the Singapore Government through the Industry Alignment Fund—Industry Collaboration Projects Grant. This research was conducted at Singtel Cognitive and Artificial Intelligence Lab for Enterprises (SCALE@NTU), which is a collaboration between Singapore Telecommunications Limited (Singtel) and Nanyang Technological University (NTU). Team KawaguchiLab (Track 5) was supported by JSPS KAKENHI under Grant JP17H01762. Team WHU&AutoNavi (Track 6) was supported by the National Key Research and Development Program of China under Grant 2016YFB0502202. Team YAI (Tracks 6 and 7) was supported by the Ministry of Science and Technology (MOST) of Taiwan under Grant MOST 110-2634-F-155-001.Peer reviewe

A multimodal cell census and atlas of the mammalian primary motor cortex

ABSTRACT We report the generation of a multimodal cell census and atlas of the mammalian primary motor cortex (MOp or M1) as the initial product of the BRAIN Initiative Cell Census Network (BICCN). This was achieved by coordinated large-scale analyses of single-cell transcriptomes, chromatin accessibility, DNA methylomes, spatially resolved single-cell transcriptomes, morphological and electrophysiological properties, and cellular resolution input-output mapping, integrated through cross-modal computational analysis. Together, our results advance the collective knowledge and understanding of brain cell type organization: First, our study reveals a unified molecular genetic landscape of cortical cell types that congruently integrates their transcriptome, open chromatin and DNA methylation maps. Second, cross-species analysis achieves a unified taxonomy of transcriptomic types and their hierarchical organization that are conserved from mouse to marmoset and human. Third, cross-modal analysis provides compelling evidence for the epigenomic, transcriptomic, and gene regulatory basis of neuronal phenotypes such as their physiological and anatomical properties, demonstrating the biological validity and genomic underpinning of neuron types and subtypes. Fourth, in situ single-cell transcriptomics provides a spatially-resolved cell type atlas of the motor cortex. Fifth, integrated transcriptomic, epigenomic and anatomical analyses reveal the correspondence between neural circuits and transcriptomic cell types. We further present an extensive genetic toolset for targeting and fate mapping glutamatergic projection neuron types toward linking their developmental trajectory to their circuit function. Together, our results establish a unified and mechanistic framework of neuronal cell type organization that integrates multi-layered molecular genetic and spatial information with multi-faceted phenotypic properties

Dynamics of GBF1, a Brefeldin A-Sensitive Arf1 Exchange Factor at the Golgi

Trafficking through the Golgi apparatus requires members of the Arf family of GTPases, whose activation is regulated by guanine nucleotide exchange factors (GEFs). Once activated, Arf-GTP recruits effectors such as coat complexes and lipid-modifying enzymes to specific membrane sites, creating a domain competent for cargo concentration and transport. GBF1 is a peripherally associated Arf GEF involved in both endoplasmic reticulum–Golgi and intra-Golgi transport. The mechanism of GBF1 binding to membranes is unknown. As a first step to understanding the mechanism of membrane association, we constructed a yellow fluorescent protein-tagged version of GBF1 and performed fluorescence recovery after photobleaching analysis to determine its residence time on Golgi membranes. We find that GBF1 molecules are not stably associated with the Golgi but rather cycle rapidly on and off membranes. The drug brefeldin A (BFA), an uncompetitive inhibitor of the exchange reaction that binds to an Arf–GDP–Arf GEF complex, stabilizes GBF1 on Golgi membranes. Using an in vivo assay to monitor Arf1-GTP levels, we show that GBF1 exchange activity on Arf1 is inhibited by BFA in mammalian cells. These results suggest that an Arf1–GBF1–BFA complex is formed and has a longer residence time on Golgi membranes than GBF1 or Arf1 alone

Non-Steroid Anti-Inflammatory Drugs Are Better than Acetaminophen on Fever Control at Acute Stage of Fracture.

In addition to adequate surgical fixation and an aggressive rehabilitation program, pain relief is one of the most critical factors in the acute stage of fracture treatment. The most common analgesics are nonsteroid anti-inflammatory drugs and Acetaminophen, both of which relieve pain and reduce body temperature. In clinical experiences, they exhibit effective pain control; however, their influence on body temperature remains controversial. This study is aimed at determining the effects of analgesics at the acute stage of traumatic fracture by performing a clinical retrospective study of patients with fractures and a fracture animal model. The retrospective study revealed that, in the acetaminophen group, the mean value of postmedication body temperature (BT) was significantly higher than that of the premedication BT. The change in BT was highly related with the medication rather than other risk factors. Forty eight 12-week-old male Wistar rats were divided into 6 groups: a control group, fracture group, fracture-Acetaminophen group, Acetaminophen group, fracture-Arcoxia group, and Arcoxia group. Fracture rats were prepared by breaking their unilateral tibia and fibula. Their inflammation conditions were evaluated by measuring their serum cytokine level and their physiological status was evaluated by estimating their central temperature, heart rate, and mean blood pressure. The hepatic adverse effects were assessed by measuring the serum levels of aspartate aminotransferase (sGOT) and alanine aminotransferase (sGPT). The central temperature in the fracture-Acetaminophen group exceeded that in the groups fed normal saline water or Arcoxia. Accumulated hepatic injury was presented as steadily ascending curves of sGOT and sGPT. Inflammation-related cytokine levels were not higher in the Acetaminophen fracture group and were significantly lower in the fracture-Arcoxia group. Fever appeared to be aggravated by acetaminophen and more related to the elevation of hepatic enzymes than to the change in the inflammation-related cytokines. We suggest that acetaminophen may aggravate fever at the acute stage of fracture. This response is highly related to the accumulated and exacerbated side effects of hepatitis that are caused by the medication and trauma