Multi-copy gene families are especially prevalent in the male-specific region (MSY) of the mammalian Y chromosome. Copy number variations (CNV) of these Y-linked gene families have been shown to affect human and animal fertility. The PRAMEY (Preferentially expressed antigen in melanoma, Y-linked) gene family is a newly identified, bovid-specific Y-linked gene family, which codes for a cancer/testis antigen that is expressed predominantly in testis and various tumors. The PRAMEY gene family is believed to play an important role in spermatogenesis and male fertility in cattle. The objective of this study was to investigate the CNV of PRAMEY within and across breeds and to determine whether CNV was associated with reproductive traits in Holstein bulls. A quantitative real-time PCR method was applied to measure the copy number of PRAMEY among 460 bulls using a Y-linked single copy gene, DDX3Y (DEAD box polypeptide 3, Y-linked), as a reference. The median copy number of PRAMEY was 13, ranging from 2 to 31. Significant variations in PRAMEY copy number were observed among 15 breeds investigated. Holstein bulls had the lowest median copy number (12), whereas Limousin bulls possessed the highest median copy number (26). Furthermore, bulls in the taurine lineage (13) had a significantly lower median copy number than those bulls in the indicine lineage (20). Association analysis revealed that PRAMEY copy number was correlated negatively with scrotal circumference (SC), relative scrotal circumference (RLSC), percentage of normal sperm (PNS), and nonreturn rate (NRR), but had no significant association with postthaw motility (PTM), incubated motility (IM), percentage of intact acrosome (PIA), sire conception rate (SCR), or relative breeding efficiency (RBE). The data from this study indicate that CNV of the PRAMEY gene family is associated with male reproductive traits and may serve as a valuable marker for sire fertility selection at an early age in cattle.

BackgroundRecent transcriptomic analysis of the bovine Y chromosome revealed at least six multi-copy protein coding gene families, including TSPY, HSFY and ZNF280BY, on the male-specific region (MSY). Previous studies indicated that the copy number variations (CNVs) of the human and bovine TSPY were associated with male fertility in men and cattle. However, the relationship between CNVs of the bovine Y-linked HSFY and ZNF280BY gene families and bull fertility has not been investigated.ResultsWe investigated the copy number (CN) of the bovine HSFY and ZNF280BY in a total of 460 bulls from 15 breeds using a quantitative PCR approach. We observed CNVs for both gene families within and between cattle breeds. The median copy number (MCN) of HSFY among all bulls was 197, ranging from 21 to 308. The MCN of ZNF280BY was 236, varying from 28 to 380. Furthermore, bulls in the Bos taurus (BTA) lineage had a significantly higher MCN (202) of HSFY than bulls in the Bos indicus (BIN) lineage (178), while taurine bulls had a significantly lower MCN (231) of ZNF280BY than indicine bulls (284). In addition, the CN of ZNF280BY was positively correlated to that of HSFY on the BTAY. Association analysis revealed that the CNVs of both HSFY and ZNF280BY were correlated negatively with testis size, while positively with sire conception rate.ConclusionThe bovine HSFY and ZNF280BY gene families have extensively expanded on the Y chromosome during evolution. The CN of both gene families varies significantly among individuals and cattle breeds. These variations were associated with testis size and bull fertility in Holstein, suggesting that the CNVs of HSFY and ZNF280BY may serve as valuable makers for male fertility selection in cattle.

To facilitate effective targeted COVID-19 vaccination strategies, it is important to understand reasons for vaccine hesitancy where uptake is low. Artificial intelligence (AI) techniques offer an opportunity for real-time analysis of public attitudes, sentiments, and key discussion topics from sources of soft-intelligence, including social media data. In this work, we explore the value of soft-intelligence, leveraged using AI, as an evidence source to support public health research. As a case study, we deployed a natural language processing (NLP) platform to rapidly identify and analyse key barriers to vaccine uptake from a collection of geo-located tweets from London, UK. We developed a search strategy to capture COVID-19 vaccine related tweets, identifying 91,473 tweets between 30 November 2020 and 15 August 2021. The platform's algorithm clustered tweets according to their topic and sentiment, from which we extracted 913 tweets from the top 12 negative sentiment topic clusters. These tweets were extracted for further qualitative analysis. We identified safety concerns; mistrust of government and pharmaceutical companies; and accessibility issues as key barriers limiting vaccine uptake. Our analysis also revealed widespread sharing of vaccine misinformation amongst Twitter users. This study further demonstrates that there is promising utility for using off-the-shelf NLP tools to leverage insights from social media data to support public health research. Future work to examine where this type of work might be integrated as part of a mixed-methods research approach to support local and national decision making is suggested.

Background Malnutrition worsens the health of frail older adults. Current treatments for malnutrition may include prescribed oral nutritional supplements, which are multinutrient products containing macronutrients and micronutrients. Objective To assess the effectiveness and cost-effectiveness of oral nutritional supplements (with or without other dietary interventions) in frail older people who are malnourished or at risk of malnutrition. Data sources MEDLINE, EMBASE, Cochrane Library, Scopus, CINAHL (Cumulative Index to Nursing and Allied Health Literature) and grey literature were searched from inception to 13 September 2021. Review methods A systematic review and meta-analysis was conducted to evaluate the effectiveness and cost-effectiveness of oral nutritional supplements in frail older people (aged ≥ 65 years) who are malnourished or at risk of malnutrition (defined as undernutrition as per National Institute for Health and Care Excellence guidelines). Meta-analysis and network meta-analysis were undertaken, where feasible, along with a narrative synthesis. A cost-effectiveness review was reported narratively. A de novo model was developed using effectiveness evidence identified in the systematic review to estimate the cost-effectiveness of oral nutritional supplements. Results Eleven studies (n = 822 participants) were included in the effectiveness review, six of which were fully or partly funded by industry. Meta-analyses suggested positive effects of oral nutritional supplements compared with standard care for energy intake (kcal) (standardised mean difference 1.02, 95% confidence interval 0.15 to 1.88; very low quality evidence) and poor mobility (mean difference 0.03, p < 0.00001, 95% confidence interval 0.02 to 0.04; very low quality evidence) but no evidence of an effect for body weight (mean difference 1.31, 95% confidence interval –0.05 to 2.66; very low quality evidence) and body mass index (mean difference 0.54, 95% confidence interval –0.03 to 1.11; very low quality evidence). Pooled results for other outcomes were statistically non-significant. There was mixed narrative evidence regarding the effect of oral nutritional supplements on quality of life. Network meta-analysis could be conducted only for body weight and grip strength; there was evidence of an effect for oral nutritional supplements compared with standard care for body weight only. Study quality was mixed; the randomisation method was typically poorly reported. One economic evaluation, in a care home setting, was included. This was a well-conducted study showing that oral nutritional supplements could be cost-effective. Cost-effectiveness analysis suggested that oral nutritional supplements may only be cost-effective for people with lower body mass index (< 21 kg/m2) using cheaper oral nutritional supplements products that require minimal staff time to administer. Limitations The review scope was narrow in focus as few primary studies used frailty measures (or our proxy criteria). This resulted in only 11 included studies. The small evidence base and varied quality of evidence meant that it was not possible to determine accurate estimates of the effectiveness or cost-effectiveness of oral nutritional supplements. Furthermore, only English-language publications were considered. Conclusions Overall, the review found little evidence of oral nutritional supplements having significant effects on reducing malnutrition or its adverse outcomes in frail older adults. Future work Future research should focus on independent, high-quality, adequately powered studies to investigate oral nutritional supplements alongside other nutritional interventions, with longer-term follow-up and detailed analysis of determinants, intervention components and cost-effectiveness. Study registration This study is registered as PROSPERO CRD42020170906. Funding This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 51. See the NIHR Journals Library website for further project information.