Background: The consistency of effects of lemborexant (LEM), a dual orexin-receptor antagonist, on sleep maintenance variables across 2 phase 3 studies with contrasting populations was compared. Methods: E2006-G000-304 (Study 304; NCT02783729) and E2006-J086-311 (Study 311; NCT04549168) were 1-month, randomized, double-blind, placebo (PBO)-controlled studies evaluating LEM 10mg (LEM10) in adults with insomnia disorder. Global Study 304 (N=1006; PBO, n=208; LEM10, n=269) enrolled participants of any race (≥55y); Study 311 (N=193; PBO, n=100; LEM10, n=93) participants were exclusively Chinese (≥18y). Pairs of polysomnograms were conducted at baseline and after the first/last 2 doses of the 1-month treatment. Change from baseline in sleep efficiency (SE [%]), wake-after-sleep-onset (WASO [min]), and total-sleep-time (TST [min]) were analyzed. Results: Mean baseline sleep parameters: Study 304: SE, 67.9–68.9; WASO, 111.8–114.8; TST, 325.1–330.7; Study 311: SE, 69.4–70.3; WASO, 79.3-–85.8; TST, 333.2–336.7. Least squares mean [standard error] increases from baseline were significantly larger with LEM10 vs PBO (P<0.001) for SE (Study 304, 8.0 [0.7]; Study 311, 7.1 [1.4]) and TST (38.9 [3.7]; 32.8 [6.9]), as were decreases in WASO (-25.4 [3.1]; -17.8 [4.8]). Most treatment-emergent adverse events were mild–moderate. Conclusions: Short-term LEM10 treatment consistently improved objective sleep maintenance in patients with insomnia of different races.

The need for collaborative and transparent sharing of COVID-19 clinical trial and large-scale observational study data to accelerate scientific discovery and inform clinical practice is critical. Responsible data-sharing requires addressing challenges associated with data privacy and confidentiality, data linkage, data quality, variable harmonization, data formats, and comprehensive metadata documentation to produce a high-quality, contextually rich, findable, accessible, interoperable, and reusable (FAIR) dataset. This communication explores the experiences and lessons learned from sharing National Heart Lung and Blood Institute (NHLBI) COVID-19 clinical trial (including adaptive platform trials) and cohort study datasets through the NHLBI BioData Catalyst® (BDC) ecosystem, focusing on the challenges and successes of harmonizing these datasets for broader research use. Our findings highlight the importance of establishing standardized data formats, adopting common data elements and creating and maintaining robust data governance structures that address common challenges (i.e., data privacy and data-sharing limitations resulting from informed consent). These efforts resulted in a set of comprehensive and interoperable datasets from 5 clinical trials and 13 cohort studies that will enable downstream reuse in analyses and collaborations. The principles and strategies outlined, derived through experience with consortia data, can lay the groundwork for advancing collaborative and efficient data sharing.

We present the third data release from the Parkes Pulsar Timing Array (PPTA) project. The release contains observations of 32 pulsars obtained using the 64-m Parkes ‘Murriyang’ radio telescope. The data span is up to 18 yr with a typical cadence of 3 weeks. This data release is formed by combining an updated version of our second data release with $\sim$3 yr of more recent data primarily obtained using an ultra-wide-bandwidth receiver system that operates between 704 and 4032 MHz. We provide calibrated pulse profiles, flux density dynamic spectra, pulse times of arrival, and initial pulsar timing models. We describe methods for processing such wide-bandwidth observations and compare this data release with our previous release.

Background: Although unapproved by the FDA for treating insomnia, trazodone is commonly prescribed in the US partly due to lack of scheduling, hence it’s perceived as safer than z-drugs and benzodiazepines. This study investigated trazodone abuse/dependence potential and safety risks. Methods: Cases involving trazodone or benzodiazepines (temazepam, triazolam, estazolam) frequently prescribed for insomnia were identified from the FDA Adverse Events Reporting System (FAERS), National Forensic Laboratory Information System (NFLIS) for confiscation data, and the American Association of Poison Control Centers’-National Poison Data System (AAPCC-NPDS). Drug-related falls risk was assessed from claims databases. Results: FAERS included 11,228 trazodone and 5120 benzodiazepine reports. Of these, drug-abuse and drug-dependence cases with trazodone were lower than benzodiazepines (drug-abuse: 6.4%/12.6%; drug-dependence: 1.1%/3.6%). Serious cases (81.8%/83.9%) and deaths (35.4%/36.0%), were similar between trazodone and benzodiazepines. NFLIS reported 612/1,575,874 (0.04%) drug-seizure cases that included trazodone. AAPCC-NPDS reported 22,225/1,446,011 (1.54%) total case mentions of trazodone/all pharmaceuticals and 8445 trazodone-related single-exposure cases. Falls risk (1year-period) in Medicare beneficiaries ≥65y and commercially-insured enrollees ≥18y was reported for trazodone and benzodiazepines: Medicare, 9.5%/11.3%; Commercially-insured: 4.6%/3.7%. Conclusions: Trazodone has abuse/dependence potential and important safety risks. Given limited data from well-controlled studies and off-label use, re-evaluation of trazodone prescribing rates in patients with insomnia is warranted.

The great demographic pressure brings tremendous volume of beef demand. The key to solve this problem is the growth and development of Chinese cattle. In order to find molecular markers conducive to the growth and development of Chinese cattle, sequencing was used to determine the position of copy number variations (CNVs), bioinformatics analysis was used to predict the function of ZNF146 gene, real-time fluorescent quantitative polymerase chain reaction (qPCR) was used for CNV genotyping and one-way analysis of variance was used for association analysis. The results showed that there exists CNV in Chr 18: 47225201-47229600 (5.0.1 version) of ZNF146 gene through the early sequencing results in the laboratory and predicted ZNF146 gene was expressed in liver, skeletal muscle and breast cells, and was amplified or overexpressed in pancreatic cancer, which promoted the development of tumour through bioinformatics. Therefore, it is predicted that ZNF146 gene affects the proliferation of muscle cells, and then affects the growth and development of cattle. Furthermore, CNV genotyping of ZNF146 gene was three types (deletion type, normal type and duplication type) by Real-time fluorescent quantitative PCR (qPCR). The association analysis results showed that ZNF146-CNV was significantly correlated with rump length of Qinchuan cattle, hucklebone width of Jiaxian red cattle and heart girth of Yunling cattle. From the above results, ZNF146-CNV had a significant effect on growth traits, which provided an important candidate molecular marker for growth and development of Chinese cattle.

This study evaluated the impact of three distinct diets; perennial ryegrass (GRS), perennial ryegrass/white clover (CLV) and total mixed ration (TMR), on the sensory properties and volatile profile of whole milk powder (WMP). The samples were evaluated using a hedonic sensory acceptance test (n = 99 consumers) and by optimised descriptive profiling (ODP) using trained assessors (n = 33). Volatile profiling was achieved by gas chromatography mass spectrometry using three different extraction techniques; headspace solid phase micro-extraction, thermal desorption and high capacity sorptive extraction. Significant differences were evident in both sensory perception and the volatile profiles of the WMP based on the diet, with WMP from GRS and CLV more similar than WMP from TMR. Consumers scored WMP from CLV diets highest for overall acceptability, flavour and quality, and WMP from TMR diets highest for cooked flavour and aftertaste. ODP analysis found that WMP from TMR diets had greater caramelised flavour, sweet aroma and sweet taste, and that WMP from GRS diets had greater cooked aroma and cooked flavour, with WMP derived from CLV diets having greater scores for liking of colour and creamy aroma. Sixty four VOCs were identified, twenty six were found to vary significantly based on diet and seventeen of these were derived from fatty acids; lactones, alcohols, aldehydes, ketones and esters. The abundance of δ-decalactone and δ-dodecalactone was very high in WMP derived from CLV and GRS diets as was γ-dodecalactone derived from a TMR diet. These lactones appeared to influence sweet, creamy, and caramelised attributes in the resultant WMP samples. The differences in these VOC derived from lipids due to diet are probably further exacerbated by the thermal treatments used in WMP manufacture.

Background: Despite a higher prevalence of traumatic spinal cord injury (TSCI) amongst Canadian Indigenous peoples, there is a paucity of studies focused on Indigenous TSCI. We present the first Canada-wide study comparing TSCI amongst Canadian Indigenous and non-Indigenous peoples. Methods: This study is a retrospective analysis of prospectively-collected TSCI data from the Rick Hansen Spinal Cord Injury Registry (RHSCIR) from 2004-2019. We divided participants into Indigenous and non-Indigenous cohorts and compared them with respect to demographics, injury mechanism, level, severity, and outcomes. Results: Compared with non-Indigenous patients, Indigenous patients were younger, more female, less likely to have higher education, and less likely to be employed. The mechanism of injury was more likely due to assault or transportation-related trauma in the Indigenous group. The length of stay for Indigenous patients was longer. Indigenous patients were more likely to be discharged to a rural setting, less likely to be discharged home, and more likely to be unemployed following injury. Conclusions: Our results suggest that more resources need to be dedicated for transitioning Indigenous patients sustaining a TSCI to community living and for supporting these patients in their home communities. A focus on resources and infrastructure for Indigenous patients by engagement with Indigenous communities is needed.

The most westerly Pacific island chain, running from Taiwan southwards through the Philippines, has long been central in debates about the origins and early migrations of Austronesian-speaking peoples from the Asian mainland into the islands of Southeast Asia and Oceania. Focusing on the Cagayan Valley of northern Luzon in the Philippines, the authors combine new and published radiocarbon dates to underpin a revised culture-historical synthesis. The results speak to the initial contacts and long-term relationships between Indigenous hunter-gatherers and immigrant Neolithic farmers, and the question of how the early speakers of Malayo-Polynesian languages spread into and through the Philippines.