bluuebunny/crossref_metadata_2025 huggingface dataset:
Histone deacetylase 1 and 2 play essential roles in alveolar macrophage homeostasis
Authors: Lai Wenlong , Luo Maocai , Li Xiaoguang , He Zhimin , Wu Tao , Wu Li
Published: May 2024

Abstract

Alveolar macrophages (AMs) are the primary lung-resident macrophages that play a pivotal role in pathogen clearance and surfactant homeostasis. The precise molecular mechanisms that maintaining AM homeostasis remain incompletely understood. Histone deacetylase (HDAC) 1 and 2 are pleiotropic enzymes removing acetyl moieties from histone proteins, facilitating transcriptional repression via chromatin condensation.Hdac1andHdac2exhibit a broad tissue distribution and modulate various cellular processes across multiple tissues. In this study, we examined the role ofHdac1andHdac2in AM homeostasis. By usingCd11c-Cre andLyz2-Cre mouse strain to mediate deletion ofHdac1andHdac2in AMs, we found simultaneous loss of bothHdac1andHdac2caused profound defect of AMs. These HDACs deficient mice spontaneously developed pulmonary alveolar proteinosis syndrome and lost resistance to influenza virus. We further found up-regulation of pro-apoptotic proteins in AMs with HDACs defect, which caused apoptosis of AM. Taken together, these observations shed light on the roles ofHdac1andHdac2as key epigenetic regulators in maintaining integrity of the AMs.
Are the Next-Generation Pathogenicity Predictors Applicable to Cancer?
Authors: Ostroverkhova Daria , Sheng Yiru , Panchenko Anna
Published: May 2024

Next-generation pathogenicity predictors are designed to identify pathogenic mutations in genetic disorders but are increasingly used to detect driver mutations in cancer. Despite this, their suitability for cancer is not fully established. Here we have assessed the effectiveness of next-generation pathogenicity predictors when applied to cancer by using a comprehensive experimental benchmark of cancer driver and neutral mutations. Our findings indicate that state-of-the-art methods AlphaMissense and VARITY demonstrate commendable performance despite generally underperforming compared to cancer-specific methods. This is notable considering that these methods do not explicitly incorporate cancer-specific information in their training and have made concerted efforts to prevent data leakage from the human-curated training and test sets. Nevertheless, it should be mentioned that a significant limitation of using pathogenicity predictors for cancer arises from their inability to detect cancer potential driver mutations specific for a particular cancer type.
Oseltamivir (Tamiflu), a Commonly Prescribed Antiviral Drug, Mitigates Hearing Loss in Mice
Authors: Sailor-Longsworth Emma , Lutze Richard D. , Ingersoll Matthew A. , Kelmann Regina G. , Ly Kristina , Currier Duane , Chen Taosheng , Zuo Jian , Teitz Tal
Published: May 2024

Hearing loss affects up to 10% of all people worldwide, but currently there is only one FDA-approved drug for its prevention in a subgroup of cisplatin-treated pediatric patients. Here, we performed an unbiased screen of 1,300 FDA-approved drugs for protection against cisplatin-induced cell death in an inner ear cell line, and identified oseltamivir phosphate (brand name Tamiflu), a common influenza antiviral drug, as a top candidate. Oseltamivir phosphate was found to be otoprotective by oral delivery in multiple established cisplatin and noise exposure mouse models. The drug conferred permanent hearing protection of 15-25 dB SPL for both female and male mice. Oseltamivir treatment reduced in mice outer hair cells death after cisplatin treatment and mitigated cochlear synaptopathy after noise exposure. A potential binding protein, ERK1/2, associated with inflammation, was shown to be activated with cisplatin treatment and reduced by oseltamivir cotreatment in cochlear explants. Importantly, the number of infiltrating immune cells to the cochleae in mice post noise exposure, were significantly reduced with oseltamivir treatment, suggesting an anti-inflammatory mechanism of action. Our results support oseltamivir, a widespread drug for influenza with low side effects, as a promising otoprotective therapeutic candidate in both cisplatin chemotherapy and traumatic noise exposure.
Network approach reveals preferential T-cell and macrophage association with α-linked β-cells in early stage of insulitis in NOD mice
Authors: Balasenthilkumaran Nirmala V. , Whitesell Jennifer C. , Pyle Laura , Friedman Rachel , Kravets Vira
Published: May 2024

One of the challenges in studying islet inflammation – insulitis – is that it is a transient phenomenon. Traditional reporting of the insulitis progression is based on cumulative, donor-averaged values of leucocyte density in the vicinity of pancreatic islets, that hinders intra- and inter-islet heterogeneity of disease progression. Here, we aimed to understand why insulitis is non-uniform, often with peri-insulitis lesions formed on one side of an islet. To achieve this, we demonstrated applicability of network theory in detangling intra-islet multi-cellular interactions during insulitis. Specifically, we asked the question “what is unique about regions of the islet which interact with immune cells first”. This study utilized the non-obese diabetic mouse model of type one diabetes and examined the interplay among α-, β-, T-cells, myeloid cells, and macrophages in pancreatic islets during the progression of insulitis. Disease evolution was tracked based on T/β cell ratio in individual islets. In the early stage, we found that immune cells are preferentially interacting with α-cell-rich regions of an islet. At the islet periphery α-linked β-cells were found to be targeted significantly more compared to those without α-cell neighbors. Additionally, network analysis revealed increased T-myeloid, and T-macrophage interactions with all β-cells.
On the completeness of existing RNA fragment structures
Authors: Hong Xu , Zhan Jian , Zhou Yaoqi
Published: May 2024

Success in protein structure prediction by the deep learning method AlphaFold 2 naturally gives arise the question if we can do the same for RNA structure prediction. One reason for the success in protein structure prediction is that the structural space of proteins at the fragment level has been nearly complete for many years. Here, we examined the completeness of RNA fragment structural space at dimeric, trimeric, tetrameric, and pentameric levels. We showed that the RNA structural space is not even complete at the di-nucleotide level, whereas the exponential increase of new structural fragments is observed at tetrameric and pentameric levels. Moreover, the number of backbone fragments found in RNA (2510) is far smaller than the number of backbone fragments found in proteins (6652). This further suggests that a structural space currently observed in RNA is far from complete, considering that the RNA backbone (6 torsion angles) has more degrees of freedom than the protein backbone (3 torsion angles with one nearly fixed). In addition, we found that the three-atom representation (one backbone atom C4’ and two sidechain atoms C1’ and N1) has the lowest number of structural fragments, suggesting it as the most “stable” structural frame for building up the entire RNA structure.
Collagen I is a critical organizer of scarring and CNS regeneration failure
Authors: Bi Yihui , Duan Wenxiu , Silver Jerry
Published: May 2024

Although axotomized neurons retain the ability to initiate the formation of growth cones and attempt to regenerate after spinal cord injury, the scar area formed as a result of the lesion in most adult mammals contains a variety of reactive cells that elaborate multiple extracellular matrix and enzyme components that are not suitable for regrowth1,2. Newly migrating axons in the vicinity of the scar utilize upregulated LAR family receptor protein tyrosine phosphatases, such as PTPσ, to associate with extracellular chondroitin sulphate proteoglycans (CSPGs), which have been discovered to tightly entrap the regrowing axon tip and transform it into a dystrophic non-growing endball. The scar is comprised of two compartments, one in the lesion penumbra, the glial scar, composed of reactive microglia, astrocytes and OPCs; and the other in the lesion epicenter, the fibrotic scar, which is made up of fibroblasts, pericytes, endothelial cells and inflammatory cells. While the fibrotic scar is known to be strongly inhibitory, even more so than the glial scar, the molecular determinants that curtail axon elongation through the injury core are largely uncharacterized. Here, we show that one sole member of the entire family of collagens, collagen I, creates an especially potent inducer of endball formation and regeneration failure. The inhibitory signaling is mediated by mechanosensitive ion channels and RhoA activation. Staggered systemic administration of two blood-brain barrier permeable-FDA approved drugs, aspirin and pirfenidone, reduced fibroblast incursion into the complete lesion and dramatically decreased collagen I, as well as CSPG deposition which were accompanied by axonal growth and considerable functional recovery. The anatomical substrate for robust axonal regeneration was provided by laminin producing GFAP+and NG2+bridging cells that spanned the wound. Our results reveal a collagen I-mechanotransduction axis that regulates axonal regrowth in spinal cord injury and raise a promising strategy for rapid clinical application.
Age-dependent variation of aedeagal morphology inAgabus uliginosusand the status ofA. lotti(Coleoptera, Dytiscidae)
Authors: Dettner Konrad , Kovács Zsolt , Rewicz Tomasz , Csabai Zoltan
Published: May 2024

The taxonomic status ofAgabus lottiwithin theAgabus uliginosusspecies group has been a subject of debate due to morphological similarities and lack of molecular data. In this study, we conducted a comprehensive morphological and molecular analysis of specimens from Central Europe, focusing on the Hungarian population. Morphological comparisons of genital structures revealed age-dependent variations, suggesting a gradual transition fromA. lottitoA. uliginosus. Molecular analysis of COI sequences further supported this hypothesis, showing minimal genetic differences among most specimens, with only one individual exhibiting distinctiveness. Therefore,A. lottishould be regarded as a junior synonym ofA. uliginosus. Our findings also highlight the need for additional multi-marker studies covering a broader geographic range and including both molecular and morphological approaches to elucidate the taxonomic and phylogenetic relationships within this species group. The inclusion of Hungarian samples notably enriched the diversity of haplotypes, emphasizing the importance of expanding sampling efforts in future research.
HIV BG505 SOSIP.664 trimer with 3M-052-AF/alum induces human autologous tier-2 neutralizing antibodies
Authors: Hahn William O , Parks K. Rachael , Shen Mingchao , Ozorowski Gabriel , Janes Holly , Ballweber-Fleming Lamar , Woodward Davis Amanda S , Duplessis Chris , Tomai Mark , Dey Antu K , Sagawa Zachary K. , De Rosa Stephen C , Seese Aaron , Siddaramaiah Latha Kallur , Stamatatos Leonidas , Lee Wen-Hsin , Sewall Leigh M , Karlinsey Dalton , Turner Hannah L , Rubin Vanessa , Furth Sarah , MacPhee Kellie , Duff Michael , Corey Lawrence , Keefer Michael C , Edupuganti Srilatha , Frank Ian , Maenza Janine , Baden Lindsey R , Hyrien Ollivier , Sanders Rogier W. , Moore John P. , Ward Andrew B , Tomaras Georgia D , Montefiori David C , Rouphael Nadine , McElrath M Juliana
Published: May 2024

Stabilized trimers preserving the native-like HIV envelope structure may be key components of a preventive HIV vaccine regimen to induce broadly neutralizing antibodies (bnAbs). We evaluated trimeric BG505 SOSIP.664 gp140, formulated with a novel TLR7/8 signaling adjuvant, 3M-052-AF/Alum, for safety, adjuvant dose-finding and immunogenicity in a first-in-healthy adult (n=17), randomized, placebo-controlled trial (HVTN 137A). The vaccine regimen appeared safe. Robust, trimer-specific antibody, B-cell and CD4+ T-cell responses emerged post-vaccination. Five vaccinees developed serum autologous tier-2 nAbs (ID50 titer, 1:28-1:8647) after 2-3 doses targeting C3/V5 and/or V1/V2/V3 Env regions by electron microscopy and mutated pseudovirus-based neutralization analyses. Trimer-specific, B-cell-derived monoclonal antibody activities confirmed these results and showed weak heterologous neutralization in the strongest responder. Our findings demonstrate the clinical utility of the 3M-052-AF/alum adjuvant and support further improvements of trimer-based Env immunogens to focus responses on multiple broad nAb epitopes.

KEY TAKEAWAY/TAKE-HOME MESSAGES

HIV BG505 SOSIP.664 trimer with novel 3M-052-AF/alum adjuvant in humans appears safe and induces serum neutralizing antibodies to matched clade A, tier 2 virus, that map to diverse Env epitopes with relatively high titers. The novel adjuvant may be an important mediator of vaccine response.
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

Objectives

Neonatal 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.

Methods

A 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.

Results

Ten 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.

Conclusions

A 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 Known

Chyme 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 New

A 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

Central 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

Objective

We aimed to investigate the circadian rhythm of patients undergoing gynaecological surgery using activity log data.

Methods

This 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.

Results

Patients 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.

Conclusion

Postoperative 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

Background

Life’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.

Objective

To 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.

Design

Population-based, cross-sectional study.

Setting

Various locations in the United States.

Participants

This 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).

Method

The 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.

Result

Among 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).

Limitation

Because estimates are based on single measures, fluctuations over time could not be determined.

Conclusion

These 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

Sliding 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

The 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

FAM19A5, 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

It 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

Background

Most 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.

Methods

An 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.

Results

Although 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.

Conclusions

Staff 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

Background

The role of circulating metabolites on child development is understudied. We investigated associations between children’s serum metabolome and early childhood development (ECD).

Methods

Untargeted 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.

Results

Twenty-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).

Conclusion

Serum 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.

Funding

Supported 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

We 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

How 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.
Deciphering the ferroptosis pathways in dorsal root ganglia of Friedreich ataxia models. The role of LKB1/AMPK, KEAP1, and GSK3β in the impairment of the NRF2 response
Authors: Sanz-Alcázar Arabela , Portillo-Carrasquer Marta , Delaspre Fabien , Pazos-Gil Maria , Tamarit Jordi , Ros Joaquim , Cabiscol Elisa
Published: May 2024

Friedreich ataxia (FA) is a rare neurodegenerative disease caused by decreased levels of the mitochondrial protein frataxin. Frataxin has been related in iron homeostasis, energy metabolism, and oxidative stress. Ferroptosis has recently been shown to be involved in FA cellular degeneration; however, its role in dorsal root ganglion (DRG) sensory neurons, the cells that are affected the most and the earliest, is mostly unknown. In this study, we used primary cultures of frataxin-deficient DRG neurons as well as DRG from the FXNI151Fmouse model to study ferroptosis and its regulatory pathways. A lack of frataxin induced upregulation of transferrin receptor 1 and decreased ferritin and mitochondrial iron accumulation, a source of oxidative stress. However, there was impaired activation of NRF2, a key transcription factor involved in the antioxidant response pathway. Decreased total and nuclear NRF2 explains the downregulation of both SLC7A11 (a member of the system Xc, which transports cystine required for glutathione synthesis) and glutathione peroxidase 4, responsible for increased lipid peroxidation, the main markers of ferroptosis. Such dysregulation could be due to the increase in KEAP1 and pGSK3β (Tyr216), which promote cytosolic localization and degradation of NRF2. Moreover, there was a deficiency in the LKB1/AMPK pathway, which would also impair NRF2 activity. AMPK acts as a positive regulator of NRF2 and it is activated by the upstream kinase LKB1. The levels of LKB1 were reduced when frataxin decreased, in agreement with reduced pAMPK (Thr172), the active form of AMPK. SIRT1, a known activator of LKB1, was also reduced when frataxin decreased. In conclusion, this study demonstrated that frataxin deficiency in DRG neurons disrupts iron homeostasis and the intricate regulation of molecular pathways affecting NRF2 activation and the cellular response to oxidative stress, leading to ferroptosis.
Prevalence of a growth mindset among introductory astronomy students
Authors: Prescott Moire K. M. , Madson Laura , Way Sandra M. , Sanderson Kelly N.
Published: May 2024

While many previous studies have indicated that encouraging a growth mindset can improve student learning outcomes, this conclusion’s applicability to college-level astronomy classrooms remains poorly understood owing to the variation in students’ overall and domain-specific learning attitudes. To address this, we surveyed undergraduate students in an introductory astronomy class about their attitudes towards learning astronomy over the course of five semesters. Overall, students felt an affinity for astronomy, felt moderately competent, perceived astronomy to be intermediate in terms of difficulty, and agreed strongly with standard statements reflecting a “growth mindset,” i.e., the belief that intelligence is malleable rather than fixed from birth. Their responses were stable over the course of the semester and did not appear to depend strongly on student demographics. The unexpected start of the COVID-19 pandemic and the associated shift to all-virtual learning correlated with a drop in their affinity for astronomy, a small decrease in their perceived competence, and an increase in the perceived difficulty of the topic. Their overall learning mindset showed negligible change during this time, emphasizing the stability of their belief in a growth mindset as compared to other measured learning attitudes. However, more nuanced questions about their behaviors and interpretations in the classroom, about how they felt “in the moment,” and about what factors were most important for their success in the class revealed significantly lower alignment with a growth mindset. This suggests that while introductory astronomy students may believe that they have a growth mindset, this mindset is not necessarily reflected in their self-reported classroom behaviors or measured responses to actual learning challenges.

Published by the American Physical Society
2024
Three-dimensional isotropic droplets in Rydberg-dressed Bose gases
Authors: Zhu Hao , Ma Yu-Quan , Bai Wen-Kai , Yu Yan-Mei , Ye Fang-Fu , Li Yong-Yao , Zhuang Lin , Liu Wu-Ming
Published: May 2024

We predict a scheme for the creation of isotropic three-dimensional quantum droplets in Rydbeg-dressed Bose gases, which contain both repulsive contact interactions and attractive soft-core interactions. Via manipulating laser detuning, the droplet size and particle number density could be engineered. Quantum fluctuation induced Lee-Huang-Yang (LHY) correction should be considered to stabilize droplets when LHY energy is comparable to the mean-field energy. Self-trapped droplets possess flat-top density distribution for a large particle number, and the collective excitations are calculated to determine the self-evaporation threshold. We further distinguish quantum droplets from solitons according to condensate compressibility. Finally, the dynamic stability of droplets is examined by pairwise-droplet collision. Our system could realize the most dilute quantum droplets, and establish a promising platform for further simulating topological nontrivial droplets.

Published by the American Physical Society
2024
Phase control of nonlinear Breit-Wheeler pair creation
Authors: Barbosa B. , Vranic M. , Weichman K. , Ramsey D. , Palastro J. P.
Published: May 2024

Electron-positron pair creation occurs throughout the universe in the environments of extreme astrophysical objects, such as pulsar magnetospheres and black hole accretion disks. The difficulty of emulating these environments in the laboratory has motivated the use of ultrahigh-intensity laser pulses for pair creation. Here we show that the phase offset between a laser pulse and its second harmonic can be used to control the relative transverse motion of electrons and positrons created in the nonlinear Breit-Wheeler process. Analytic theory and particle-in-cell simulations of a head-on collision between a two-color laser pulse and electron beam predict that with an appropriate phase offset, the electrons will drift in one direction and the positrons in the other. The resulting current may provide a collective signature of nonlinear Breit-Wheeler, while the spatial separation resulting from the relative motion may facilitate isolation of positrons for subsequent applications or detection.

Published by the American Physical Society
2024
Exploring the effects of a one-dimensional periodic potential on a three-dimensional topological insulator
Authors: Koop Albert , Altmann Alexander , Kozlov Dmitriy A. , Mikhailov Nikolay N. , Dvoretskii Sergey A. , Weiss Dieter
Published: May 2024

High mobility two-dimensional systems with superposed 1D lateral periodic potentials exhibit characteristic commensurability (Weiss) oscillations that reflect the interplay of the cyclotron radius at the Fermi level and the superlattice period. Here, we impose a one-dimensional periodic potential on strained HgTe, which is a strong 3D topological insulator. By tuning the Fermi level with top gates, the effects of the artificial potential can be studied in the bulk gap, where only Dirac surface states exist, in the conduction band, and in the valence band, where Dirac electrons and holes coexist. On the electron side, we observe clear commensurability oscillations whose period is governed by the carrier density of the top-surface Dirac electrons. Unexpectedly, weak commensurability oscillations are also observed in the valence band with a period that depends on both electron and hole density.

Published by the American Physical Society
2024
Broken seniority symmetry in the semimagic proton mid-shell nucleus
Rh95
Authors: Das B. , Cederwall B. , Qi C. , Górska M. , Regan P. H. , Aktas Ö. , Albers H. M. , Banerjee A. , Chishti M. M. R. , Gerl J. , Hubbard N. , Jazrawi S. , Jolie J. , Mistry A. K. , Nowacki F. , Polettini M. , Yaneva A. , Ahmed U. , Alhomaidhi S. , Algora A. , Appleton C. , Arici T. , Bagchi S. , Benzoni G. , Benito J. , Blazhev A. , Boutachkov P. , Bracco A. , Bruce A. M. , Brunet M. , Canavan R. , Davinson T. , Dickel T. , Esmaylzadeh A. , Fraile L. M. , Haettner E. , Hall O. , Häfner G. , Heggen H. , Hornung Ch. , Hucka J. P. , John P. R. , Kahl D. , Karayonchev V. , Kern R. , Knöbel R. , Korgul A. , Kosir G. , Kojouharov I. , Kostyleva D. , Kuzminchuk N. , Kurz N. , Liotta R. , Lozeva R. , Mikolajczuk M. , Mukha I. , Napiralla P. , Page R. , Petrache C. M. , Pietralla N. , Pietri S. , Plaß W. R. , Podolyák Zs. , Régis J.-M. , Rudigier M. , Rösch H. , Ruotsalainen P. , Sahin E. , Sánchez-Tembleque V. , Schaffner H. , Scheidenberger C. , Schirru F. , Sexton L. , Singh B. S. Nara , Sharma A. , Shearman R. , Si M. , Tanaka Y. K. , Vasiljević J. , Vesić J. , Vilhena J. , Weick H. , Wollersheim H. J. , Werner V. , Wiederhold J. , Witt W. , Woods P. J. , Zimba G. , Zhao J.
Published: May 2024

Lifetime measurements of low-lying excited states in the semimagic (N=50) nucleus Rh95 have been performed by means of the fast-timing technique. The experiment was carried out using γ-ray detector arrays consisting of LaBr3(Ce) scintillators and germanium detectors integrated into the DESPEC experimental setup commissioned for the Facility for Antiproton and Ion Research () Phase-0, Darmstadt, Germany. The excited states in Rh95 were populated primarily via the β decays of Pd95 nuclei, produced in the projectile fragmentation of a 850 MeV/nucleon Xe124 beam impinging on a 4g/cm2Be9 target. The deduced electromagnetic E2 transition strengths for the γ-ray cascade within the multiplet structure depopulating from the isomeric Iπ=21/2+ state are found to exhibit strong deviations from predictions of standard shell model calculations which feature approximately conserved seniority symmetry. In particular, the observation of a strongly suppressed E2 strength for the 13/2+→9/2+ ground state transition cannot be explained by calculations employing standard interactions. This remarkable result may require revision of the nucleon-nucleon interactions employed in state-of-the-art theoretical model calculations, and might also point to the need for including three-body forces in the Hamiltonian.

Published by the American Physical Society
2024
Evolution of structure and spectroscopic properties of a new 1,3-diacetylpyrene polymorph with temperature and pressure
Authors: Zwolenik A. , Tchoń D. , Makal A.
Published: May 2024

A new polymorph of 1,3-diacetylpyrene has been obtained from its melt and thoroughly characterized using single-crystal X-ray diffraction, steady-state UV–Vis spectroscopy and periodic density functional theory calculations. Experimental studies covered the temperature range from 90 to 390 K and the pressure range from atmospheric to 4.08 GPa. Optimal sample placement in a diamond anvil cell according to our previously presented methodology ensured over 80% data coverage up to 0.8 Å for a monoclinic sample. Unrestrained Hirshfeld atom refinement of the high-pressure crystal structures was successful and anharmonic behavior of carbonyl oxygen atoms was observed. Unlike the previously characterized polymorph, the structure of 2°AP-β is based on infinite π-stacks of antiparallel 2°AP molecules. 2°AP-β displays piezochromism and piezofluorochromism which are directly related to the variation in interplanar distances within the π-stacking. The importance of weak intermolecular interactions is reflected in the substantial negative thermal expansion coefficient of −55.8 (57) MK−1 in the direction of C—H...O interactions.