MiR-145-5p regulates granulosa cell proliferation by targeting the SET gene in KGN cells.

MiR-145-5p has been implicated in the development and progression of various disorders, and it is primarily recognized as a tumor suppressor in numerous cancers types. Its expression has been reported to decrease in the granulosa cells of patients with polycystic ovarian syndrome (PCOS). This study aimed to investigate whether miR-145-5p plays a role in granulosa cell proliferation and to shed light on the underlying pathological mechanisms of follicular development in patients with PCOS. Follicular fluid samples were collected from patients with PCOS and healthy individuals. The Cell Counting Kit-8 and bromodeoxyuridine assays were performed to assess KGN cell proliferation. The expression of miR-145-5p was significantly decreased in PCOS granulosa cells than in control cells, whereas the expression of SET was increased. Furthermore, miR-145-5p suppressed the proliferation of KGN cells. SET was identified as a direct target of miR-145-5p. Additionally, SET promoted the proliferation of KGN cells, and knockdown of SET counteracted the effect of the miR-145-5p inhibitor. Therefore, miR-145-5p regulates granulosa cell proliferation by targeting the SET in KGN cells; this process may be a potential pathological pathway that contributes to follicular developmental disorders in PCOS.

A hierarchical reinforcement learning model explains individual differences in attentional set shifting.

Attentional set shifting refers to the ease with which the focus of attention is directed and switched. Cognitive tasks, such as the widely used CANTAB IED, reveal great variation in set shifting ability in the general population, with notable impairments in those with psychiatric diagnoses. The attentional and learning processes underlying this cognitive ability and how they lead to the observed variation remain unknown. To directly test this, we used a modelling approach on two independent large-scale online general-population samples performing CANTAB IED, with one including additional psychiatric symptom assessment. We found a hierarchical model that learnt both feature values and dimension attention best explained the data and that compulsive symptoms were associated with slower learning and higher attentional bias to the first relevant stimulus dimension. These data showcase a new methodology to analyse data from the CANTAB IED task, as well as suggest a possible mechanistic explanation for the variation in set shifting performance, and its relationship to compulsive symptoms.

Comparison of dental movements in digital setups created by orthodontists and "3shape design service®" engineers: A cross-sectional study.

INTRODUCTION: The demand for faster and invisible orthodontic treatments has led to the increased use of clear aligners, facilitated by advancements in digital treatment planning. This study aims to evaluate the reliability of digital orthodontic setups performed by orthodontists compared to those by 3Shape Design Service®engineers. MATERIAL AND METHODS: A monocentric, cross-sectional observational study was conducted at Bretonneau Hospital from October 2022 to May 2023. All patients meeting the inclusion criteria and willing to participate were included in the study. Intraoral scans were used to create treatment setups using the Ortho System® software, performed by both orthodontists and 3Shape® engineers. The primary objective was to compare the dental movements (rotation, intrusion, extrusion, buccolingual inclination, tipping, mesiodistal translation and buccolingual translation) between the two groups. Secondary objectives included the number of teeth displaced, aligners needed, interproximal enamel reduction and number of attachments placed. RESULTS: Nineteen patients with mild to moderate malocclusion were included. Statistically significant differences were found in tooth displacements between the two groups with engineers executing greater dental movements for derotation (4.9±2.6 vs. 3.7±2.3), tipping (0.79±0.69 vs. 0.26±0.44), bucco-lingual (0.40±0.26 vs. 0.08±0.11) and mesio-distal translations (0.31±0.20 vs. 0.20±0.17). Secondary measures showed no significant differences except for the number of teeth displaced (15.32±5.21 vs. 9.68±4.82), which was higher in the 3Shape group. DISCUSSION: While digital setups by engineers showed more significant tooth movements, the practical impact on mild malocclusion treatment was minimal. This study highlights the need for precise treatment objectives and consideration of overcorrection practices. CONCLUSION: For mild malocclusions, outsourcing setups to 3Shape engineers can be an alternative to in-office setups by orthodontists. However, further studies are needed to evaluate setup reliability for more complex malocclusions.

Optimal Training Positive Sample Size Determination for Deep Learning with a Validation on CBCT Image Caries Recognition.

Objectives: During deep learning model training, it is essential to consider the balance among the effects of sample size, actual resources, and time constraints. Single-arm objective performance criteria (OPC) was proposed to determine the optimal positive sample size for training deep learning models in caries recognition. Methods: An expected sensitivity (PT) of 0.6 and a clinically acceptable sensitivity (P0) of 0.5 were applied to the single-arm OPC calculation formula, yielding an optimal training set comprising 263 carious teeth. U-Net, YOLOv5n, and CariesDetectNet were trained and validated using clinically self-collected cone-beam computed tomography (CBCT) images that included varying quantities of carious teeth. To assess performance, an additional dataset was utilized to evaluate the accuracy of caries detection by both the models and two dental radiologists. Results: When the number of carious teeth reached approximately 250, the models reached the optimal performance levels. U-Net demonstrated superior performance, achieving accuracy, sensitivity, specificity, F1-Score, and Dice similarity coefficients of 0.9929, 0.9307, 0.9989, 0.9590, and 0.9435, respectively. The three models exhibited greater accuracy in caries recognition compared to dental radiologists. Conclusions: This study demonstrated that the positive sample size of CBCT images containing caries was predictable and could be calculated using single-arm OPC.

Context-Dependent and Locus-Specific Role of H3K36 Methylation in Transcriptional Regulation.

H3K36 methylation is a critical histone modification involved in transcription regulation. It involves the mono (H3K36me1), di (H3K36me2), and/or tri-methylation (H3K36me3) of lysine 36 on histone H3 by methyltransferases. In yeast, Set2 catalyzes all three methylation states. By contrast, in higher eukaryotes, at least eight methyltransferases catalyze different methylation states, including SETD2 for H3K36me3 and the NSD family for H3K36me2 in vivo. Both Set2 and SETD2 interact with the phosphorylated CTD of RNA Pol II, which links H3K36 methylation to transcription. In yeast, H3K36me3 and H3K36me2 peak at the 3' ends of genes. In higher eukaryotes, this is also true for H3K36me3 but not for H3K36me2, which is enriched at the 5' ends of genes and intergenic regions, suggesting that H3K36me2 and H3K36me3 may play different regulatory roles. Whether H3K36me1 demonstrates preferential distribution remains unclear. H3K36me3 is essential for inhibiting transcription elongation. It also suppresses cryptic transcription by promoting histone deacetylation by the histone deacetylases Rpd3S (yeast) and variant NuRD (higher eukaryotes). H3K36me3 also facilitates DNA methylation by DNMT3B, thereby preventing spurious transcription initiation. H3K36me3 not only represses transcription since it promotes the activation of mRNA and cryptic promoters in response to environmental changes by targeting the histone acetyltransferase NuA3 in yeast. Further research is needed to elucidate the methylation state- and locus-specific functions of H3K36me1 and the mechanisms that regulate it.

Identification of key hub genes in knee osteoarthritis through integrated bioinformatics analysis.

Knee osteoarthritis (KOA) is a common chronic joint disease globally. Synovial inflammation plays a pivotal role in its pathogenesis, preceding cartilage damage. Identifying biomarkers in osteoarthritic synovial tissues holds promise for early diagnosis and targeted interventions. Gene expression profiles were obtained from the Gene Expression Omnibus database. Subsequent analyses included differential expression gene (DEG) analysis and weighted gene co-expression network analysis (WGCNA) on the combined datasets. We performed functional enrichment analysis on the overlapping genes between DEGs and module genes and constructed a protein-protein interaction network. Using Cytoscape software, we identified hub genes related to the disease and conducted gene set enrichment analysis on these hub genes. The CIBERSORT algorithm was employed to evaluate the correlation between hub genes and the abundance of immune cells within tissues. Finally, Mendelian randomization analysis was utilized to assess the potential of these hub genes as biomarkers. We identified 46 differentially expressed genes (DEGs), comprising 20 upregulated and 26 downregulated genes. Using WGCNA, we constructed a gene co-expression network and selected the most relevant modules, resulting in 24 intersecting genes with the DEGs. KEGG enrichment analysis of the intersecting genes identified the IL-17 signaling pathway, associated with inflammation, as the most significant pathway. Cytoscape software was utilized to rank the candidate genes, with JUN, ATF3, FOSB, NR4A2, and IL6 emerging as the top five based on the Degree algorithm. A nomogram model incorporating these five genes, supported by ROC curve analysis, validated their diagnostic efficacy. Immune infiltration and correlation analysis revealed that macrophages were significantly associated with JUN (p < 0.01), FOSB (p < 0.01), and NR4A2 (p < 0.05). Additionally, T follicular helper cells showed significant associations with ATF3 (p < 0.05), FOSB (p < 0.05), and JUN (p < 0.05). Mendelian randomization analysis provided strong evidence linking JUN (IVW: OR = 0.910, p = 0.005) and IL6 (IVW: OR = 1.024, p = 0.026) with KOA. Through the utilization of various bioinformatics analysis methods, we have pinpointed key hub genes relevant to knee osteoarthritis. These findings hold promise for advancing pre-symptomatic diagnostic strategies and enhancing our understanding of the biological underpinnings behind knee osteoarthritis susceptibility genes.

Development of a health state classification system for the PedsQL™ 4.0 Generic Core Scales for preference-based valuation in Australia.

OBJECTIVES: Pediatric Quality of Life InventoryTM Version 4.0 Generic Core Scales (PedsQL GCS), comprising 23 items covering four sub-scales (physical, emotional, social, and school functioning), is a widely applied generic measure of childhood health-related quality of life, but does not provide health utilities for cost-effectiveness-based decision-making. This study aimed to develop a reduced item version of PedsQL GCS amenable to health utility derivation in Australia. METHODS: Data sources were two cohorts of the Longitudinal Study of Australian Children, including proxy responses for all PedsQL GCS versions (Toddlers, Young Children, Children, Teens), and the CheckPoint sample containing child self-report to the Children version. Three analytic samples were: CheckPoint sample (n=1,874); Mallinson sample containing one measurement per child from one of the Young Children, Children or Teens versions (n=7,855); and Toddlers sample (n=7,401). Exploratory and confirmatory factor analyses assessed dimensionality. Psychometric analyses used Rasch and classical criteria on three randomly selected subsamples (n=500) per sample. Item selection prioritised psychometric performance in CheckPoint sample, also considering performance in other samples and conceptual content. RESULTS: Dimensionality assessments did not generate an alternative empirical structure for the measure, and psychometric analyses were conducted on the original four sub-scales. The selected items were: 'Get aches and pains' for physical functioning; 'Feel sad/blue' for emotional functioning; 'Other kids not friends' for social functioning; and 'Keeping up with school work' for school functioning. CONCLUSIONS: The final four-item set, pending further psychometric validation and valuation, can generate health utilities from the widely used PedsQL GCS to inform cost-effectiveness-based decision-making.

Improvement of Single Event Transient Effects for a Novel AlGaN/GaN High Electron-Mobility Transistor with a P-GaN Buried Layer and a Locally Doped Barrier Layer.

In this paper, a novel AlGaN/GaN HEMT structure with a P-GaN buried layer in the buffer layer and a locally doped barrier layer under the gate (PN-HEMT) is proposed to enhance its resistance to single event transient (SET) effects while also overcoming the degradation of other characteristics. The device operation mechanism and characteristics are investigated by TCAD simulation. The results show that the peak electric field and impact ionization at the gate edges are reduced in the PN-HEMT due to the introduced P-GaN buried layer in the buffer layer. This leads to a decrease in the peak drain current (Ipeak) induced by the SET effect and an improvement in the breakdown voltage (BV). Additionally, the locally doped barrier layer provides extra electrons to the channel, resulting in higher saturated drain current (ID,sat) and maximum transconductance (gmax). The Ipeak of the PN-HEMT (1.37 A/mm) is 71.8% lower than that of the conventional AlGaN/GaN HEMT (C-HEMT) (4.85 A/mm) at 0.6 pC/µm. Simultaneously, ID,sat and BV are increased by 21.2% and 63.9%, respectively. Therefore, the PN-HEMT enhances the hardened SET effect of the device without sacrificing other key characteristics of the AlGaN/GaN HEMT.

Reproductive Performance of the Alpine Plant Species Ranunculus kuepferi in a Climatic Elevation Gradient: Apomictic Tetraploids Do Not Show a General Fitness Advantage over Sexual Diploids.

Previous studies on the mountain plant Ranunculus kuepferi concluded that apomictic self-compatible tetraploids have experienced a niche shift toward a colder climate during the Holocene, which suggests a fitness advantage over the sexual, self-sterile diploid parents under cold and stressful high-mountain conditions. However, there is still a lack of information on whether reproductive development would be advantageous for tetraploids. Here, we report on microsporogenesis, megagametogenesis, the dynamics of flower and seed development, and the consequences for reproductive success in a common garden experiment along a 1000 m climatic elevation gradient and in natural populations. Flower buds were initiated in the year preceding anthesis and passed winter in a pre-meiotic stage. Flower morphology differed in the known cytotype-specific way in that tetraploid flowers produced about twice as many carpels and fewer petals, stamens, and pollen grains than diploid flowers. Tetraploids developed precociously aposporous embryo sacs and showed a high rate of developmental disturbances. Sexual seed formation prevailed in diploids and pseudogamous apomixis in tetraploids. Along the elevation gradient, stigma pollen load, pollen performance, and seed output decreased. Combinations of reproductive traits, namely, bypass of meiosis irregularities and uniparental reproduction, might have promoted the vast expansion of apomictic R. kuepferi lines across the European Alps.

Animal pollination contributes to more than half of citrus production.

Animal pollination is crucial for the reproduction and economic viability of a wide range of crops. Despite the existing data, the extent to which citrus crops depend on pollinators to guarantee fruit production still needs to be determined. Here, we described the composition of potential pollinators in citrus (Citrus spp.) from the main growing areas of Argentina; moreover, we combined Bayesian models and empirical simulations to assess the contribution of animal pollination on fruit set and yield ha-1 in different species and cultivars of lemons, grapefruits, mandarins, and oranges. Honeybee (A. mellifera L.) was the most commonly observed potential pollinator, followed by a diverse group of insects, mainly native bees. Regardless of citrus species and cultivars, the probability of flowers setting fruit in pollinated flowers was 2.4 times higher than unpollinated flowers. Furthermore, our simulations showed that about 60% of the citrus yield ha-1 can be attributable to animal pollination across all species and cultivars. Therefore, it is crucial to maintain environments that support pollinator diversity and increase consumer and to producer awareness and demand in order to ensure the significant benefits of animal pollination in citrus production.

Estimating the prevalence of osteoporosis using ranked-based methodologies and Manitoba's population-based BMD registry.

Osteoporosis is a metabolic bone disorder that is characterized by reduced bone mineral density (BMD) and deterioration of bone microarchitecture. Osteoporosis is highly prevalent among women over 50, leading to skeletal fragility and risk of fracture. Early diagnosis and treatment of those at high risk for fracture is very important in order to avoid morbidity, mortality and economic burden from preventable fractures. The province of Manitoba established a BMD testing program in 1997. The Manitoba BMD registry is now the largest population-based BMD registry in the world, and has detailed information on fracture outcomes and other covariates for over 160,000 BMD assessments. In this paper, we develop a number of methodologies based on ranked-set type sampling designs to estimate the prevalence of osteoporosis among women of age 50 and older in the province of Manitoba. We use a parametric approach based on finite mixture models, as well as the usual approaches using simple random and stratified sampling designs. Results are obtained under perfect and imperfect ranking scenarios while the sampling and ranking costs are incorporated into the study. We observe that rank-based methodologies can be used as cost-efficient methods to monitor the prevalence of osteoporosis.

Evaluating thermal comfort indices for outdoor spaces on a university campus.

This study evaluates the applicability of three thermal comfort indices-Physiologically Equivalent Temperature (PET), Standard Effective Temperature (SET), and Universal Thermal Climate Index (UTCI)-in various outdoor environments on the campus of Xi'an University, China. Meteorological data were collected on sunny days using a portable weather station at a height of 1.5 m, and subjective questionnaires were administered to 25 healthy university students over three months to gather Thermal Sensation Votes (TSV) and Thermal Comfort Votes (TCV). The study was conducted at four distinct outdoor locations: a lakeside area (Location 1), a shaded path (Location 2), a sports field (Location 3), and a plaza (Location 4). PET, SET, and UTCI values were calculated from the collected data using Rayman software. The analysis revealed significant differences in thermal comfort across the four locations, with the highest proportion of subjects feeling hot at the sports field (54.4%) and the highest proportion feeling cold at the lakeside (39%). The shaded path had the highest proportion of subjects feeling comfortable (79.4%), while the lakeside had the lowest (60.1%). The results indicated that SET underestimated thermal sensation at Locations 1, 3, and 4, necessitating calibration. PET was suitable for Locations 2, 3, and 4 but failed to reflect the thermal sensation at Location 1 due to prolonged sun exposure. In contrast, UTCI demonstrated applicability across all locations. To enhance accuracy, revised indices SET' and PET' were formulated using the mean-median method, providing more precise thermal comfort assessments. These findings underscore the limitations of SET and PET under specific conditions and highlight the robustness of UTCI, offering valuable insights for urban planning and design aimed at improving outdoor thermal comfort and well-being.

Identification of key regulatory genes involved in myelination after spinal cord injury by GSEA analysis.

Multilayer dense myelin tissue provides insulating space and nutritional support for axons in healthy spinal cord tissue. Oligodendrocyte precursor cells (OPCs) are the main glial cells that complement myelin loss in the central nervous system and play an important role in the repair of spinal cord injury (SCI). However, the regulation of axonal remyelination after SCI is still insufficient. In this study, we focused on the changes in genes related to myelin repair after rat hemisection SCI by gene set enrichment analysis (GSEA). Key genes proteolipid protein 1 (Plp1), hexosaminidase subunit alpha (Hexa), and hexosaminidase subunit beta (Hexb) during remyelination after SCI were found. Through quantitative real-time polymerase chain reaction (qPCR) experiments, we confirmed that within 28 days after rat hemisection SCI, the mRNA expression of gene Plp1 gradually decreased, while the expressions of gene Hexa and Hexb gradually increased, which was consistent with RNA sequencing results. In vitro, we performed EdU proliferation assays on OPC cell line OLN-93 and primary rat OPCs. We found that interference of Plp1 promoted OPC proliferation, while interference of Hexa and Hexb inhibited OPC proliferation. In addition, we performed in vitro differentiation experiments on primary rat OPCs. By measuring myelin sheath branch outgrowth and the fluorescence intensity of the mature myelin sheath marker myelin basic protein (MBP), we found that interference of Hexa or Hexb promoted OPC differentiation and maturation, but interference of Plp1 inhibited this process. Finally, we injected Hexb siRNA in vivo and found that interfering Hexb could improve motor movements and myelin regeneration after SCI in rats. Our results provide new target genes that can selectively regulate the proliferation and differentiation of endogenous OPCs, providing new ideas for promoting remyelination and functional recovery after SCI.

National stakeholder consultation on how to measure care home residents' quality of life.

Background: The Developing research resources And minimum data set for Care Homes' Adoption and use or DACHA study aims to create a prototype minimum data set combining residents' information recorded by care homes with their data held in health and social care data sets. The DACHA minimum data set will contain information on quality of life. Internationally and in the UK, there is no consensus on collecting information on quality of life in a standardised format equivalent to the consensus for health measures. Objective: This paper describes an online consultation with stakeholder representatives about how to measure the quality of life of residents in UK older-adult care homes, for inclusion in the DACHA minimum data set. Design: We drew on principles of the Delphi technique, identifying participants knowledgeable about living, working in and visiting care homes, and preference scoring. Setting: We used a bespoke online research engagement platform (Thiscovery, www.thiscovery.org, Cambridge, UK) to engage the participants. Participants: Participants included care home staff and managers, old age specialists (clinical/research), commissioners/providers/regulators, primary care professionals, relatives/family carers of care home residents. The consultation is complementary to DACHA's research and patient and public involvement and engagement activities, which have involved people living in care homes; thus, care home residents were not included in this consultation. Results: The first round asked 30 participants to rank the most important principles and domains to consider when measuring quality of life in care homes. Responses to round 1 informed the selection of quality of life measures that round 2 (September 2022) participants were asked to report their familiarity with and confidence in a range of outcome measures all of which met the criteria identified as important in round 1. Recruitment was extended in round 2, and 72 individuals participated. Conclusion: Based on the rankings and the qualitative feedback in round 2, we included four of the shortlisted quality of life outcome measures in DACHA's prototype minimum data set for care homes. The qualitative feedback suggested a shared understanding across the different representative groups about the strengths and limitations of the selected measures. This work makes an important contribution, understanding the opportunities that quality of life measures pose for different stakeholder groups as regular users of care home resident data. Future work: In future DACHA work, interviews and focus groups will collect further data about the perceptions of care home staff who completed measures during the pilot study and about the usefulness of the data collected via these measures. The quality-of-life section of the DACHA minimum data set can contribute to informing similar care home data sets internationally. Funding: This article presents independent research funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme as award number NIHR127234.

The Developing research resources And minimum data set for Care Homes' Adoption and use study aims to explore how we can link together and safely share information about older care home residents so that care settings (such as hospitals, GPs and care homes) can best meet their needs. To work towards this aim, we are identifying what information is most important to capture and share in a 'minimum data set'. Having information about care home residents' quality of life was recognised by residents, their family members, care providers, researchers and health professionals as something that is important to measure. Quality of life describes the general well-being of an individual and is more than whether someone is healthy or not. By measuring a person's quality of life, it is possible to explore how changes in their care or innovations within their care home affect their sense of well-being. We asked care home staff, experts on ageing, healthcare workers, local authority officials and family members of residents what is important to know about residents' quality of life. In the first online survey (June 2022), we learned from 30 individuals that any quality of life measurement tool needs to be simple, reliable and meeting the needs of the residents. In our second survey (September 2022), 72 individuals gave us their thoughts about different quality of life measurement tools. They told us about whether they would use these tools, how much confidence they have in them, and what they see as strengths and weaknesses of the tools. This feedback helped us choose the right tools to measure quality of life in care homes and make sure they are a good fit for care home residents.

Single-neuron representation of nonsymbolic and symbolic number zero in the human medial temporal lobe.

The number zero holds a special status among numbers, indispensable for developing a comprehensive number theory.1,2,3,4 Despite its importance in mathematics, the neuronal foundation of zero in the human brain is unknown. We conducted single-neuron recordings in neurosurgical patients5,6,7 while they made judgments involving nonsymbolic number representations (dot numerosity), including the empty set, and symbolic numbers (Arabic numerals), including numeral zero. Neurons showed responsiveness to either the empty set or numeral zero, but not both. Neuronal activity to zero in both nonsymbolic and symbolic formats exhibited a numerical distance effect, indicating that zero representations are integrated together with countable numerosities and positive integers at the low end of the number line.8,9 A boundary in neuronal coding existed between the nonsymbolic empty set and small numerosities, correlating with the relative difficulty in discriminating numerosity zero behaviorally. Conversely, no such boundary was found for symbolic zero activity, suggesting that symbolic representations integrate zero with other numerals along the number line, reconciling its outlier role. The status of zero as a special nonsymbolic numerical quantity is reflected in the activity of neurons in the human brain, which seems to serve as a scaffold for more advanced representations of zero as a symbolic number.

Analysis of coupling effect between TID and SET in SOI Tri-Gate nanowire field-effect transistors.

This study investigates the response of nanowire field-effect transistors (NWFETs) to total ionizing dose (TID), single-event transient (SET), and their coupling effects in junctionless (JL), inversion (IM), and junctionless accumulation (AC) modes. The degradation of the three modes under irradiation and the effect of device bias configuration on the electrical properties of NWFETs are analyzed, and the different effects of SET on the three modes are compared. On this basis, the influence of TID on SET current generation and the charge collection mechanism are studied, and the changes in peak current, pulse width, and collected charge of transient current under different TIDs are compared. The results show that JL mode has the worst resistance to TID and SET coupling effects, followed by IM and AC modes. .

Identification of two heterogeneous subtypes of hepatocellular carcinoma with distinct pathway activities and clinical outcomes based on gene set variation analysis.

Background: High heterogeneity is an essential feature of malignant tumors. This study aims to reveal the drivers of hepatocellular carcinoma heterogeneity for prognostic stratification and to guide individualized treatment. Methods: Omics data and clinical data for two HCC cohorts were derived from the Cancer Genome Atlas (TCGA) and the International Cancer Genome Atlas (ICGC), respectively. CNV data and methylation data were downloaded from the GSCA database. GSVA was used to estimate the transcriptional activity of KEGG pathways, and consensus clustering was used to categorize the HCC samples. The pRRophetic package was used to predict the sensitivity of samples to anticancer drugs. TIMER, MCPcounter, quanTIseq, and TIDE algorithms were used to assess the components of TME. LASSO and COX analyses were used to establish a prognostic gene signature. The biological role played by genes in HCC cells was confirmed by in vitro experiments. Results: We classified HCC tissues into two categories based on the activity of prognostic pathways. Among them, the transcriptional profile of cluster A HCC is similar to that of normal tissue, dominated by cancer-suppressive metabolic pathways, and has a better prognosis. In contrast, cluster B HCC is dominated by high proliferative activity and has significant genetic heterogeneity. Meanwhile, cluster B HCC is often poorly differentiated, has a high rate of serum AFP positivity, is prone to microvascular invasion, and has shorter overall survival. In addition, we found that mutations, copy number variations, and aberrant methylation were also crucial drivers of the differences in heterogeneity between the two HCC subtypes. Meanwhile, the TME of the two HCC subtypes is also significantly different, which offers the possibility of precision immunotherapy for HCC patients. Finally, based on the prognostic value of molecular subtypes, we developed a gene signature that could accurately predict patients' OS. The riskscore quantified by the signature could evaluate the heterogeneity of HCC and guide clinical treatment. Finally, we confirmed through in vitro experiments that RFPL4B could promote the progression of Huh7 cells. Conclusion: The molecular subtypes we identified effectively exposed the heterogeneity of HCC, which is important for discovering new effective therapeutic targets.

Behavioral, Cognitive, and Functional Risk Factors for Repeat Hospital Episodes Among Medicare-Medicaid Dually Eligible Adults Receiving Long-Term Services and Supports.

Repeat hospitalizations adversely impact the well-being of adults dually eligible for Medicare and Medicaid in the United States. This study aimed to identify behavioral, cognitive, and functional characteristics associated with the risk of a repeat hospital episode (HE) among the statewide population of dually eligible adults in Maryland receiving long-term services and supports prior to an HE between July 2018 and May 2020. The odds of experiencing a repeat HE within 30 days after an initial HE were positively associated with reporting difficulty with hearing (adjusted odds ratio, AOR: 1.10 [95% confidence interval: 1.02-1.19]), being easily distractible (AOR: 1.09 [1.00-1.18]), being self-injurious (AOR: 1.33 [1.09-1.63]), and exhibiting verbal abuse (AOR: 1.15 [1.02-1.30]). Conversely, displaying inappropriate public behavior (AOR: 0.62 [0.42-0.92]) and being dependent for eating (AOR: 0.91 [0.83-0.99]) or bathing (AOR: 0.79 [0.67-0.92]) were associated with reduced odds of a repeat HE. We also observed differences in the magnitude and direction of these associations among adults 65 years of age or older relative to younger counterparts.

Outcome reporting in studies on pregnant women with cardiac disease: a systematic review: Outcomes in studies on pregnancy and heart disease.

BACKGROUND: Although considerable variation in the reporting and definition of outcomes in cardio-obstetric studies is known, the extent of this variation has not been documented. The primary objective of this systematic review was to highlight this variation and inform the development of a Core Outcome Set for studies on Cardiac disease in Pregnancy (COSCarP). METHODS: Medline, Embase, Web of Science and Cochrane Central databases were searched from 1980 to 2018 to identify all English-language publications on pregnancy and heart disease. Title/abstract screening and data extraction which included details on the study, patient population, and all reported outcomes, was performed in duplicate by two reviewers. As the aim of the review was to identify variation in outcome reporting, risk-of-bias assessment was not performed. The study protocol was registered on PROSPERO (CRD42016038218). RESULTS: The final analysis included 422 cardio-obstetric studies. Maternal mortality or survival were reported in 232/422 studies, with inconsistency in terms of cause of death [all-cause (n=65), cardiac (n=55) or obstetric (n=10)] or timeframe (ranging from in-hospital mortality (n=11) to mortality 5 years following pregnancy). In 95/232 studies (41%), the cause and timeframe were not specified. Similar inconsistencies in reporting and definitions were noted for outcomes such as heart failure (n=298), perinatal loss (n=296), fetal growth (n=221), bleeding (n=205), arrhythmias (n=202), preterm birth (n=191), thromboembolism (n=153) and hypertensive disorders (n=122). Functioning / life-impact and adverse effects of treatment were sparingly reported in cardio-obstetric studies. CONCLUSIONS: This systematic review hopes to create awareness among cardio-obstetric teams about the inconsistencies in reporting and defining outcomes which makes it difficult to compare studies and perform meta-analyses. COSCarP which is being developed through international consensus between patients and care-providers will provide cardio-obstetrics teams with a minimal set of outcomes to be reported in future cardio-obstetric studies.

Validation of the imperial psychedelic predictor scale.

BACKGROUND: Access to psychedelic drugs is liberalizing, yet responses are highly unpredictable. It is therefore imperative that we improve our ability to predict the nature of the acute psychedelic experience to improve safety and optimize potential therapeutic outcomes. This study sought to validate the 'Imperial Psychedelic Predictor Scale' (IPPS), a short, widely applicable, prospective measure intended to be predictive of salient dimensions of the psychedelic experience. METHODS: Using four independent datasets in which the IPPS was completed prospectively - two online surveys of 'naturalistic' use (N = 741, N = 836) and two controlled administration datasets (N = 30, N = 28) - we conducted factor analysis, regression, and correlation analyses to assess the construct, predictive, and convergent validity of the IPPS. RESULTS: Our approach produced a 9-item scale with good internal consistency (Cronbach's α = 0.8) containing three factors: set, rapport, and intention. The IPPS was significantly predictive of 'mystical', 'challenging', and 'emotional breakthrough' experiences. In a controlled administration dataset (N = 28), multiple regression found set and rapport explaining 40% of variance in mystical experience, and simple regression found set explained 16% of variance in challenging experience. In another (N = 30), rapport was related to emotional breakthrough explaining 9% of variance. CONCLUSIONS: Together, these data suggest that the IPPS is predictive of relevant acute features of the psychedelic experience in a broad range of contexts. We hope that this brief 9-item scale will be widely adopted for improved knowledge of psychedelic preparedness in controlled settings and beyond.