bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluating the Efficacy and Safety of Neonatal Chyme Reinfusion Therapy: A Feasibility Study using a Novel Medical Device
Authors: Ludlow E. , Harrington T. , Davidson R. , Davidson J. , Aikins K. , O’Grady G. , Bissett I. 
Published: May 2024

AbstractObjectivesNeonatal and pediatric intestinal failure related to enterostomy is an infrequent but burdensome condition associated with substantial morbidity and mortality. This study presents the development and clinical validation of a novel device to resolve these problems, by formalizing a safe and efficient enterostomy chyme reinfusion technique.MethodsA novel neonatal chyme reinfusion device was designed and manufactured (termed the ‘The Insides Neo’, The Insides Company, New Zealand), prior to validation in a feasibility study in tertiary neonatal intensive care centres. Neonates with double enterostomy were recruited and commenced on chyme reinfusion therapy using the novel device to test safety, efficacy, tolerability, and usability within nursing workflows. Device and clinical outcomes were recorded along with nursing feedback. Registered under the ANZCTR, identifier no. ACTRN12621000835842p.ResultsTen neonates were recruited across two centres, with a median usage duration of 37.5 (range 12-84) days. Following initiation of therapy, rate of weight gain increased from mean 68.8 ± 37.4 to 197 ± 25.0 g/week (p=0.024). Of the 7/10 neonates on PN at commencement of therapy, 4/7 were able to wean and achieve enteral autonomy. All neonates tolerated the device with uniformly positive nursing feedback and minimal time to learn and incorporate the novel device into nursing workflows. There were no device-related adverse events.ConclusionsA novel device was developed and validated to be safe and effective at performing chyme reinfusion therapy in neonates. This device is anticipated to improve the clinical care and outcomes neonatal patients with double enterostomies.What is KnownChyme reinfusion is widely accepted and is a standard of care in many centres who care for neonates with double enterostomy’s.The manual application of chyme reinfusion has led to low adoption despite the many benefits.What is NewA new device that automates the process of chyme reinfusion that overcomes many of the barriers outlined in the literature.Uniformly positive nursing feedback that streamlines the Neonatal Intensive Care Unit (NICU) workflow.
Rare genetic variation in VE-PTP is associated with central serous chorioretinopathy, venous dysfunction and glaucoma
Authors: Rämö Joel T , Gorman Bryan , Weng Lu-Chen , Jurgens Sean J , Singhanetr Panisa , Tieger Marisa G , van Dijk Elon HC , Halladay Christopher W , Wang Xin , Brinks Joost , Choi Seung Hoan , Luo Yuyang ,   FinnGen, Program VA Million Veteran, Pyarajan Saiju , Nealon Cari L , Gorin Michael B , Wu Wen-Chih , Sobrin Lucia , Kaarniranta Kai , Yzer Suzanne , Palotie Aarno , Peachey Neal S , Turunen Joni A , Boon Camiel JF , Ellinor Patrick T , Iyengar Sudha K , Daly Mark J , Rossin Elizabeth J 
Published: May 2024

AbstractCentral serous chorioretinopathy (CSC) is a fluid maculopathy whose etiology is not well understood. Abnormal choroidal veins in CSC patients have been shown to have similarities with varicose veins. To identify potential mechanisms, we analyzed genotype data from 1,477 CSC patients and 455,449 controls in FinnGen. We identified an association for a low-frequency (AF=0.5%) missense variant (rs113791087) in the gene encoding vascular endothelial protein tyrosine phosphatase (VE-PTP) (OR=2.85, P=4.5×10-9). This was confirmed in a meta-analysis of 2,452 CSC patients and 865,767 controls from 4 studies (OR=3.06, P=7.4×10-15). Rs113791087 was associated with a 56% higher prevalence of retinal abnormalities (35.3% vs 22.6%, P=8.0x10-4) in 708 UK Biobank participants and, surprisingly, with varicose veins (OR=1.31, P=2.3x10-11) and glaucoma (OR=0.82, P=6.9x10-9). Predicted loss-of-function variants in VEPTP, though rare in number, were associated with CSC in All of Us (OR=17.10, P=0.018). These findings highlight the significance of VE-PTP in diverse ocular and systemic vascular diseases.
Circadian rhythm measured by step count in patients undergoing midline laparotomy for gynaecological conditions
Authors: Lee Jung Yun , Kim Kidong , Kim Yong Beom , No Jae Hong , Suh Dong Hoon 
Published: May 2024

AbstractObjectiveWe aimed to investigate the circadian rhythm of patients undergoing gynaecological surgery using activity log data.MethodsThis is a planned secondary analysis of a randomised controlled trial dataset. The randomised controlled trial included 53 women undergoing midline laparotomy for gynaecological conditions (NCT02025387). A detailed activity log (number of steps per minute) was collected from 10 patients using a wearable activity tracker (Lifegram LA11M-BS, LG). The activity log data of the patients (N=10) were visualised by a pandas 1.4.2 documentation using google colab.ResultsPatients walked more during the day than at night, indicating a preserved circadian rhythm. Daily post-operative activity increased with the progress of the post-operative day. Nocturnal activity increased from postoperative day 3.ConclusionPostoperative activities of women who underwent midline laparotomy showed a preserved circadian rhythm.
Life’s Crucial 12: Updating and Enhancing the Life’s Essential 8 of Cardiovascular Health: A proposal from NHANES
Authors: Gou Ruoyu , Gou Yufan , Dou Danni , Li Guanghua 
Published: May 2024

AbstractBackgroundLife’s Essential 8 (LE8) is a cardiovascular health (CVH) model but does not take into account mental health, an important cardiovascular risk factor, so we constructed Life’s Crucial 12 (LC12), a comprehensive cardiovascular care model that takes CVH into account, based on LE8, and hypothesized that it would be a more reliable index of CVH, despite the additional information needed to calculate LC12.ObjectiveTo construct an integrated cardiovascular care model LC12 based on LE8 that can take Psychological Health into account, and to report the association between LC12 and stroke.DesignPopulation-based, cross-sectional study.SettingVarious locations in the United States.ParticipantsThis study was a cross-sectional study based on data from the 2005-2008 National Health and Nutrition Examination Survey (NHANES), which included 4,478 U.S. adults (≥ 20 years old).MethodThe composite cardiovascular care model LC12 with scores (range 0-100) defining low (0-49), medium (50-79) and high (80-100) CVH. Determination of stroke status was obtained by questionnaire. Associations were assessed using multivariate logistic regression models and restricted cubic spline models.ResultAmong 4,478 participants, there were 2252 female and 2226 male participants (53.136% and 46.864%, respectively), and 250 participants (5.583%) were diagnosed with stroke. The mean values of LC12, Psychological Health, Health behaviors, and Health factors scores for participants with stroke were 68.953, 52.775, and 55.451, respectively, which were lower than those of Non-Stroke participants. After fully adjusting for confounders, the ORs for the LC 12, Psychological Health, Health Behaviors, and Health Factors moderate and high groups were 0.431 (0.226,0.822), 0.212 (0.060,0.755), 0.536 (0.297, 0.967), 0.357 (0.178,0.713), 0.759 (0.552, 1.043), 0.334 (0.179, 0.623), 0.565 (0.406, 0.786), 0.533 (0.286, 0.994), which were significantly associated with the risk of stroke (P-trend< 0.05) and there was a linear trend between subgroups with different scores (P-value< 0.001). However, no nonlinear dose relationship was observed (P-Nonlinearity> 0.05).LimitationBecause estimates are based on single measures, fluctuations over time could not be determined.ConclusionThese findings suggest that Psychological Health is important in CVH. CVH status assessed by LC12 (Psychological Health, Health behaviors, Health factors) was significantly associated with the risk of developing stroke. When LC12 scores are maintained at high levels, it is beneficial to decrease the risk of stroke.Abstract Pictures
Structure of the human CTF18 clamp loader bound to PCNA
Authors: Briola Giuseppina R. , Tehseen Muhammad , Al-Amodi Amani , Nguyen Phong Quoc , Savva Christos G. , Hamdan Samir M. , De Biasio Alfredo 
Published: May 2024

AbstractSliding clamps like PCNA are crucial processivity factors for replicative polymerases, requiring specific clamp loaders for loading onto DNA. The human alternative clamp loader CTF18 interacts with the leading strand polymerase Pol ε and loads PCNA onto primer/template DNA using its RFC pentameric module. Here, we provide a structural characterization of the human CTF18 complex and its interaction with PCNA. Our cryo-EM data support that the Ctf8 and Dcc1 subunits of CTF18, which form the regulatory module interacting with Pol ε, are flexibly tethered to the RFC module. A 2.9 Å cryo-EM structure shows the RFC module bound to PCNA in an auto-inhibited conformation similar to the canonical RFC loader, marking the initial step of the clamp-loading reaction. The unique RFC1 (Ctf18) large subunit of CTF18, which shows high relative mobility, is anchored to PCNA through an atypical low-affinity PIP box in the AAA+ domain and engages the RFC5 subunit using a novel β-hairpin at the disordered N-terminus. We show that deletion of this β-hairpin impairs the CTF18−PCNA complex stability and decreases the rate of primer synthesis by Pol ε. Our research identifies distinctive structural characteristics of the human CTF18-RFC complex, providing insights into its role in PCNA loading and the stimulation of leading strand synthesis by Pol ε.
Improved accuracy for estrous cycle staging using supervised object detection
Authors: Babaev Benjamin , Goyal Saachi , Ross Rachel A 
Published: May 2024

ABSTRACTThe estrous cycle regulates reproductive events and hormone changes in female mammals and is analogous to the menstrual cycle in humans. Monitoring this cycle is necessary as it serves as a biomarker for overall health and is crucial for interpreting study results. The estrous cycle comprises four stages influenced by fluctuating levels of hormones, mainly estradiol and progesterone. Tracking the cycle traditionally relies on vaginal cytology, which categorizes stages based on three epithelial cell concentrations. However, this method has limitations, including time-consuming training and variable accuracy among researchers. To address these challenges, this study assessed the feasibility and reliability of two machine learning methods. An object detection-based machine learning model, Object Detection Estrous Staging (ODES), was employed to identify cell types throughout the estrous cycle in mice. A dataset of 555 vaginal cytology images with four different stains was annotated, with 335 images for training, 45 for validation, and 175 for testing. A novel, accurate set of rules for classification was derived by analyzing training images. ODES achieved an average accuracy of 87% in classifying cycle stages and took only 3.9 minutes to analyze 175 test images. The use of object detection machine learning significantly improved accuracy and efficiency compared to previously derived supervised image classification models (33-45% accuracy) and human accuracy (66% accuracy), refining research practices for female studies. These findings facilitate the integration of the estrous cycle into research, enhancing the quality of scientific results by allowing for efficient and accurate identification of the cycle stage.
FAM19A5 Deficiency Mitigates the Aβ Plaque Burden and Improves Cognition in Mouse Models of Alzheimer’s Disease
Authors: Park Sumi , Shahapal Anu , Yoo Sangjin , Hwang Jong-Ik , Seong Jae Young 
Published: May 2024

ABSTRACTFAM19A5, a novel secretory protein highly expressed in the brain, is potentially associated with the progression of Alzheimer’s disease (AD). However, its role in the AD brain remains unclear. Here, we investigated the potential function of FAM19A5 in the context of AD. We generated APP/PS1 mice with partial FAM19A5 deficiency, termed APP/PS1/FAM19A5+/LacZmice. Compared to control APP/PS1 mice, APP/PS1/FAM19A5+/LacZmice exhibited significantly lower Aβ plaque density, suggesting that FAM19A5 reduction mitigates Aβ plaque formation. Notably, partial FAM19A5 depletion also prolonged the lifespan of the APP/PS1 mice. To further explore the therapeutic potential of targeting FAM19A5, we developed an anti-FAM19A5 antibody. Administration of this antibody to APP/PS1 mice significantly improved their performance in the novel object recognition test, demonstrating enhanced cognitive function. This effect was reproduced in 5XFAD mice, a model of early-onset AD characterized by rapid Aβ accumulation. Additionally, anti-FAM19A5 antibody treatment in 5XFAD mice led to increased spontaneous alternation behavior in the Y-maze test, indicating improved spatial working memory. These findings suggest that anti-FAM19A5 antibodies may be a promising therapeutic strategy for AD by reducing Aβ plaques and improving cognitive function.
Age-related impacts of dementia status and subtype on accelerometry measures in older adults from the National Health and Aging Trends Study
Authors: Brown Karl , Shutes-David Andrew , Payne Sarah , Jankowski Adrienne , Wilson Katie , Seto Edmund , Tsuang Debby 
Published: May 2024

AbstractIt is likely that age, dementia status, and dementia subtype all contribute to differences in activity levels among older adults and that accelerometer devices can help us better understand these relationships. To that end, this study analyzes accelerometry data from individuals with dementia (n=104) and individuals without dementia (n=634) who participated in the National Health and Aging Trends Study (NHATS), as well as from individuals with dementia with Lewy bodies (DLB; n=12) and Alzheimer’s disease (AD; n=8) who participated in a small pilot study. In the NHATS cohort, individuals with dementia had lower daily activity counts (t = -5.449, p < 0.001), a shorter active bout length (t = -5.283, p < 0.001), and a longer resting bout length (t = 2.210, p = 0.032) at the mean age of 79 than individuals without dementia at that same age. Differences in data collection and processing prevented direct comparisons between the cohorts, but parallel analyses revealed no statistically significant differences between AD and DLB across these three measures in the smaller cohort. Studies with larger samples of subtyped individuals with dementia will be necessary to detect clinically meaningful differences, but the patterns observed in the small cohort suggest that individuals with DLB are less active, exhibit a shorter active bout length, and exhibit a longer resting bout length than individuals with AD. Taken together, these findings highlight the potential of accelerometers to gather objective activity data that could be used to aid in the early identification of dementia and, potentially, the differentiation of dementia subtypes.
‘Finding a Relationship’ Conversations Between Mental Health and Social Care Staff, and Service Users
Authors: Emery-Rhowbotham Angelica , Killaspy Helen , Eager Sharon , Lloyd-Evans Brynmor 
Published: May 2024

AbstractBackgroundMost people seek to establish romantic or intimate relationships in life, including people with mental health problems. However, this has been a neglected topic in mental health practice and research. This study aimed to investigate views of mental health and social care staff about the appropriateness of helping service users with romantic relationships, barriers to doing this, and suggestions for useful ways to support this.MethodsAn online survey comprising both closed, multiple response and free-text questions was circulated to mental health organisations across the U.K. via social media, professional networks and use of snowballing sampling. A total of 63 responses were received. Quantitative data were analysed using descriptive statistics, and are reported as frequencies and percentages. Qualitative data were interpreted using thematic analysis, using an inductive approach.ResultsAlthough most participants reported that ‘finding a relationship’ conversations were appropriate in their job role, many barriers to supporting service users were identified, including: a lack of training; concerns about professional boundaries; concerns about service user capacity and vulnerability; and concerns about being intrusive. Participant suggestions for future support included educating service users on safe dating behaviours, and practical interventions such as assisting service users to use dating sites and engage with social activities to develop social skills and meet others.ConclusionsStaff were willing to help service users seek an intimate relationship but may need specific training or guidance to facilitate this confidently and safely. This study elucidates the need for further research in this area, particularly in understanding service user perspectives, and in developing resources to support staff in this work.
Serum metabolome indicators of early childhood development in the Brazilian National Survey on Child Nutrition (ENANI-2019)
Authors: Padilha Marina , Keller Victor N. , Normando Paula , Schincaglia Raquel M. , Freitas-Costa Nathalia C. , Freire Samary S. R. , Delpino Felipe M. , de Castro Inês R. R. , Lacerda Elisa M. A. , Farias Dayana R. , Kroezen Zachary , Shanmuganathan Meera , Britz-Mckibbin Philip , Kac Gilberto 
Published: May 2024

AbstractBackgroundThe role of circulating metabolites on child development is understudied. We investigated associations between children’s serum metabolome and early childhood development (ECD).MethodsUntargeted metabolomics was performed on serum samples of 5,004 children aged 6-59 months, a subset of participants from the Brazilian National Survey on Child Nutrition (ENANI-2019). ECD was assessed using the Survey of Well-being of Young Children’s milestones questionnaire. The graded response model was used to estimate developmental age. Developmental quotient (DQ) was calculated as the developmental age divided by chronological age. Partial least square regression was used to select metabolites with a variable importance projection ≥ 1.ResultsTwenty-eight top-ranked metabolites were included in linear regression models adjusted for child’s nutritional status, diet quality and age. Interaction between these metabolites and child age was tested. Cresol sulfate (β = −0.07; adjusted-p < 0.001), hippuric acid (β = −0.06; adjusted-p < 0.001), phenylacetylglutamine (β = −0.06; adjusted-p < 0.001), and trimethylamine-N-oxide (β = −0.05; adjusted-p = 0.002) showed inverse associations with DQ. We observed opposite directions in the association of DQ for creatinine (for children aged −1 SD: β = −0.05; p =0.01; +1 SD: β = 0.05; p =0.02) and methylhistidine (−1 SD: β = - 0.04; p =0.04; +1 SD: β = 0.04; p =0.03).ConclusionSerum biomarkers, including dietary and microbial derived metabolites involved in the gut-brain axis, may potentially be used to track children at risk for developmental delays.FundingSupported by the Brazilian Ministry of Health and Brazilian National Research Council.
Past Disparities in Advance Care Planning Across Sociodemographic Characteristics and Cognition Levels in the United States
Authors: Rahemi Zahra , Bacsu Juanita-Dawne R. , Shalhout Sophia Z. , Sabet Morteza , Sirizi Delaram , Smith Matthew Lee , Adams Swann Arp 
Published: May 2024

AbstractWe aimed to examine past advance care planning (ACP) in U.S. older adults across different sociodemographic characteristics and cognition levels. We established the baseline trends from 10 years ago to assess if trends in 2024 have improved upon future data availability. We considered two legal documents in the Health and Retirement Study 2014 survey as measures for ACP: a living will and durable power of attorney for healthcare (DPOAH). Logistic regression models were fitted with outcome variables (living will, DPOAH, and both) stratified by cognition levels (dementia/impaired cognition versus normal cognition). Predictor variables included age, gender, ethnicity, race, education, marital status, rurality, everyday discrimination, social support, and loneliness. Age, ethnicity, race, education, and rurality were significant predictors of ACP (having a living will, DPOAH, and both the living will and DPOAH) across cognition levels. Participants who were younger, Hispanic, Black, had lower levels of education, or resided in rural areas were less likely to complete ACP. Examining ACP and its linkages to specific social determinants is essential to understanding disparities and educational strategies needed to facilitate ACP uptake among different population groups. Accordingly, this study aimed to examine past ACP disparities in relation to specific social determinants of health and different cognition levels. Future studies are required to evaluate whether existing disparities have improved over the last 10 years when 2024 data is released. Addressing ACP disparities among diverse populations, including racial and ethnic minorities with reduced cognition levels, is crucial for enhancing health equity and access to care.
Single cell transcriptomics of theDrosophilaembryonic salivary gland reveals not only induction but also exclusion of expression as key morphogenetic control steps
Authors: May Annabel , Röper Katja 
Published: May 2024

AbstractHow tissue shape and therefore function is encoded by the genome remains in many cases unresolved. The tubes of the salivary glands in theDrosophilaembryo start from simple epithelial placodes, specified through the homeotic factors Scr/Hth/Exd. Previous work indicated that early morphogenetic changes are prepatterned by transcriptional changes, but an exhaustive transcriptional blueprint driving physical changes was lacking. We performed single-cell-RNAseq-analysis of FACS-isolated early placodal cells, making up less than 0.4% of cells within the embryo. Differential expression analysis in comparison to epidermal cells analysed in parallel generated a repertoire of genes highly upregulated within placodal cells prior to morphogenetic changes. Furthermore, clustering and pseudo-time analysis of single-cell-sequencing data identified dynamic expression changes along the morphogenetic timeline. Our dataset provides a comprehensive resource for future studies of a simple but highly conserved morphogenetic process of tube morphogenesis. Unexpectedly, we identified a subset of genes that, although initially expressed in the very early placode, then became selectively excluded from the placode but not the surrounding epidermis, includinghth,grainyheadandtollo/toll-8. We show that maintainingtolloexpression severely compromised the tube morphogenesis.tollois likely switched off to not interfere with key Tolls/LRRs that are expressed and function in the placode.