bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neurovascular dysfunction associated with erectile dysfunction persists after long‐term recovery from simulations of weightlessness and deep space irradiation
Authors: Andrade Manuella R. , Azeez Tooyib A. , Montgomery McLane M. , Caldwell Jacob T. , Park Hyerim , Kwok Andy T. , Borg Alexander M. , Narayanan S. Anand , Willey Jeffrey S. , Delp Michael D. , La Favor Justin D. 
Published: November 2023

AbstractThere has been growing interest within the space industry for long‐duration manned expeditions to the Moon and Mars. During deep space missions, astronauts are exposed to high levels of galactic cosmic radiation (GCR) and microgravity which are associated with increased risk of oxidative stress and endothelial dysfunction. Oxidative stress and endothelial dysfunction are causative factors in the pathogenesis of erectile dysfunction, although the effects of spaceflight on erectile function have been unexplored. Therefore, the purpose of this study was to investigate the effects of simulated spaceflight and long‐term recovery on tissues critical for erectile function, the distal internal pudendal artery (dIPA), and the corpus cavernosum (CC). Eighty‐six adult male Fisher‐344 rats were randomized into six groups and exposed to 4‐weeks of hindlimb unloading (HLU) or weight‐bearing control, and sham (0Gy), 0.75 Gy, or 1.5 Gy of simulated GCR at the ground‐based GCR simulator at the NASA Space Radiation Laboratory. Following a 12–13‐month recovery, ex vivo physiological analysis of the dIPA and CC tissue segments revealed differential impacts of HLU and GCR on endothelium‐dependent and ‐independent relaxation that was tissue type specific. GCR impaired non‐adrenergic non‐cholinergic (NANC) nerve‐mediated relaxation in the dIPA and CC, while follow‐up experiments of the CC showed restoration of NANC‐mediated relaxation of GCR tissues following acute incubation with the antioxidants mito‐TEMPO and TEMPOL, as well as inhibitors of xanthine oxidase and arginase. These findings indicate that simulated spaceflight exerts a long‐term impairment of neurovascular erectile function, which exposes a new health risk to consider with deep space exploration.
Mutual Mistrust: The Multilayered Experiences at the Intersection of Healthcare and Early Parenting Among Mothers With Opioid Use Disorder
Authors: Schiff Davida M. , Muftu Serra , MacMillan Kathryn Dee L. , Work Erin C. , Hoeppner Bettina B. , Greenfield Shelly F. , Schwartz Leah , Chaiyachati Barbara , Wilens Timothy E. , Bernstein Judith A. 
Published: November 2023

Objective
The aim of the study is to explore the early parenting experiences among a cohort of postpartum individuals with opioid use disorder (OUD) both during and after the delivery hospitalization to identify areas of intervention to strengthen bonding and attachment.

Methods
Semistructured qualitative interviews with recently pregnant people with OUD assessed parenting needs, supports, and goals in the context of the demands of addiction treatment and early motherhood. Probes explored the relationship between early parenting experiences, addiction, and recovery, as well as enabling factors and barriers to mother-infant bonding. Interviews were completed between 2019 to 2020. A constant comparative methods approach was used for codebook development and analysis.

Results
Twenty-six women completed interviews a mean of 10.1 months postpartum. Twenty-four women were receiving methadone or buprenorphine treatment at delivery for OUD. Four interrelated themes emerged. Women experienced the following: (1) increased surveillance from healthcare workers who doubted their parenting ability; (2) a desire for a “normal” early parenting experience that was not disrupted by increased medical monitoring and surveillance; (3) complex and intersecting identities of being both a mother and a person in recovery; and (4) the importance of support from and advocacy by clinicians and peers to developing maternal confidence and connection.

Conclusions
Interventions are needed to improve the early parenting experiences of opioid-exposed mother-infant dyads, to address the mutual mistrust between health care providers and parents, and to provide additional supports to families. Promotion of positive attachment and parental self-efficacy should be prioritized over increased surveillance and scrutiny to sustain maternal recovery trajectories into early childhood and foster family well-being.
The Effect of Rho Kinase Inhibitors on In Vitro Human Orbital Preadipocytes
Authors: Yoo David , Horacek Meredith , Chae Min Kyung , Kim Ji Young , Bu Ping , Yoon Jin Sook 
Published: November 2023

Purpose:
To identify the effects of Rho Kinase (ROCK) inhibitor medications on human orbital adipogenesis, fibroblast proliferation, and fibrosis.

Methods:
Orbital adipose tissue was obtained from patients with Graves’ ophthalmopathy (GO) as well as controls (non-GO or normal) after informed consent was done. These tissue samples were cultured and adipogenesis was initiated. Levels of Rho Kinase as well as cellular mediators of orbital inflammation and fibrosis. The same cultures and measurements were then repeated with the use of a ROCK inhibitor (KD025-ROCK2) to assess for changes in adipogenesis as well as markers associated with inflammation and fibrosis.

Results:
Rho Kinase levels in GO tissue were more highly expressed than in controls. These levels were suppressed with the use of the ROCK inhibitor KD025. There was a dose-dependent reduction in differentiation of orbital adipocytes with the use of KD025. KD025 reduced the levels of fibrosis-related gene expression. Finally, there was a significant reduction of transforming growth factor beta mediated phosphorylation signaling pathways in the KD025-treated GO tissue.

Conclusion:
This study shows that the ROCK inhibitor, KD025, helps to reduce the expression of ROCK in GO tissue along with reducing orbital adipocyte differentiation as well as cell mediators involved in fibrosis that occurs in GO.
New Insights Into the Anatomy of the Eyelashes With Regard to Ethnic Differences Against a Clinical Background
Authors: Singh Swati , Hammer Christian M. , Paulsen Friedrich 
Published: November 2023

Background:
To investigate the root depth, root angle, and light and scanning electron microscopical anatomy of human eyelashes relevant to eyelash ablation.

Methods:
Eyelash root depth, the angle between eyelash root and skin epithelium, spatial relationship, and scanning electron microscopical features of the eyelashes were studied on 4 upper and 4 lower eyelids of Caucasian (n = 4) and Indian (n = 4) cadaver heads according to a set protocol.

Results:
There were significant differences in the mean eyelash root depth between Indians (2.3 ± 0.38 mm) and Caucasians (1.9 ± 0.26 mm; p = 0.007), as well as between upper eyelids and lower eyelids (1.9 ± 0.2 mm vs. 1.8 ± 0.1 mm). The mean angle between the lash follicle root and the skin epithelium was 75 ± 11 degrees and similar in both ethnic groups. The eyelash bulb was located close to the tarsal plate and meibomian glands and formed an angle of less than 15 degrees with the eyelash root. Scanning electron microscopy studies revealed that the eyelash bulb was 202 ± 12 μm wide in Indians and 170.6 ± 16.8 μm wide in Caucasian eyelids (p = 0.08). The eyelashes were placed more closely in Indian eyelids than in Caucasian eyelids (p = 0.03). The width of the cuticle layer varied between the hair shaft and the inner eyelid segment.

Conclusions:
There are differences in eyelash root depth, inter-eyelash distance, and cuticle thickness between Indian and Caucasian eyelids. The oblique orientation of the eyelash root and close proximity of the eyelash bulb to the tarsal plate should be kept in mind while doing the electroepilation procedure.
Impact of Facility Dog and Certified Child Life Specialist Dyad on Children’s Pain and Anxiety During Needlestick Procedures in a Pediatric Hematology Oncology Clinic Setting
Authors: Spikestein Ali , Musante Jordan , Huang Hsin-Hui , Stojanowski Morgan , Rode Diane , Pillai Pallavi , Crouch Gary D. 
Published: November 2023

Background:
Pediatric Hematology Oncology patients undergo frequent needlestick procedures, often leading to negative outcomes including pain and anxiety. Animal-assisted therapy has been shown to minimize pediatric patient distress; however, its utilization by a Certified Child Life Specialist (CCLS) to reduce patient distress has not been widely studied.

Methods:
Pediatric patients receiving needlesticks in the Hematology Oncology Clinic were enrolled between March 2018 and May 2021. Patients who had scheduled visits when the facility dog was present were assigned to the intervention group. Patients were assigned to the control group if the facility dog was not present. The primary objective was to use the Children’s Anxiety and Pain Scale to determine whether the CCLS and facility dog dyad minimized patient pain and anxiety during procedures.

Results:
A total of 285 patients, 5 to 17 years of age, were enrolled. One hundred forty-three patients were assigned the intervention and received procedural support from the CCLS and facility dog; 142 patients were assigned the control group and received support from the CCLS only. Patient-reported pain scores were significantly lower among patients who received the intervention (P=0.033).

Conclusions:
Utilization of a CCLS and facility dog dyad during painful needlestick procedures decreases patient-reported pain compared with utilization of CCLS support alone.
dFLASH; dual FLuorescent transcription factor Activity Sensor for Histone integrated live-cell reporting and high-content screening
Authors: Allen Timothy P. , Roennfeldt Alison E. , Reckdharajkumar Moganalaxmi , Liu Miaomiao , Quinn Ronald J. , Russell Darryl L. , Peet Daniel J. , Whitelaw Murray L. , Bersten David C. 
Published: November 2023

AbstractLive-cell reporting of regulated transcription factor (TF) activity has a wide variety of applications in synthetic biology, drug discovery, and functional genomics. As a result, there is high value in the generation of versatile, sensitive, robust systems that can function across a range of cell types and be adapted toward diverse TF classes. Here we present the dual FLuorescent transcription factor Activity Sensor for Histone integrated live-cell reporting (dFLASH), a modular sensor for TF activity that can be readily integrated into cellular genomes. We demonstrate readily modified dFLASH platforms that homogenously, robustly, and specifically sense regulation of endogenous Hypoxia Inducible Factor (HIF) and Progesterone receptor (PGR) activities, as well as regulated coactivator recruitment to a synthetic DNA-Binding Domain-Activator Domain fusion proteins. The dual-colour nuclear fluorescence produced normalised dynamic live-cell TF activity sensing with facile generation of high-content screening lines, strong signal:noise ratios and reproducible screening capabilities (Z’ = 0.68-0.74). Finally, we demonstrate the utility of this platform for functional genomics applications by using CRISPRoff to modulate the HIF regulatory pathway, and for drug screening by using high content imaging in a bimodal design to isolate activators and inhibitors of the HIF pathway from a ∼1600 natural product library.
Whole-genome Studies of Malagasy People Uncover Novel Body Composition Associations
Authors: Hamid Iman , Stéphie Raveloson Séverine Nantenaina , Spiral Germain Jules , Ravelonjanahary Soanorolalao , Raharivololona Brigitte Marie , Randria José Mahenina , Zafimaro Mosa , Randriambola Tsiorimanitra Aimée , Andriantsoa Rota Mamimbahiny , Andriamahefa Tojo Julio , Laza Rafidison Bodonomena Fitahiana , Mughal Mehreen , Emde Anne-Katrin , Hendershott Melissa , LeBaron von Baeyer Sarah , Wasik Kaja A. , Ranaivoarisoa Jean Freddy , Yerges-Armstrong Laura , Castel Stephane E. , Rakotoarivony Rindra 
Published: November 2023

SummaryThe majority of human genomic research studies have been conducted in European ancestry cohorts, at the loss of detecting potentially novel and globally impactful findings. Here, we present the first whole genome sequence data and genome-wide association study in a cohort of 264 Malagasy individuals from three locations on the island of Madagascar. We describe genetic variation in this Malagasy cohort, providing insight into the shared and unique patterns of genetic variation across the island. We observe phenotypic variation by location, and find high rates of hypertension particularly in the Southern Highlands as well as elevated malaria prevalence in the West Coast relative to other sites. We find a number of genetic associations with body composition traits, including many variants that are unique to African populations or populations with admixed African ancestry such as Madagascar. This study highlights the utility of including diverse populations in genomic research for the potential to gain novel insights, even with small cohort sizes. This project was conducted in partnership and consultation with local Malagasy stakeholders and serves as an example for equitable genomic research with potential impacts on our understanding of human health and disease.
Prenatal multiple micronutrient-fortified balanced energy-protein supplementation and newborn telomere length and mitochondrial DNA content: a randomized controlled efficacy trial in rural Burkina Faso
Authors: Hanley-Cook Giles T. , Bastos-Moreira Yuri , Martens Dries S. , Dailey-Chwalibóg Trenton , Toe Laeticia Celine , de Kok Brenda , Ouédraogo Lionel , Argaw Alemayehu , Tesfamariam Kokeb , Kolsteren Patrick , Huybregts Lieven , Nawrot Tim S. , Saeger Sarah De , De Boevre Marthe , Lachat Carl 
Published: November 2023

AbstractBackgroundEvidence regarding the effectiveness of prenatal nutritional supplements has mainly considered anthropometric pregnancy outcomes. The effect on markers of health and disease, such as offspring telomere length (TL) and mitochondrial DNA content (mtDNAc) is unknown.ObjectivesWe assessed the efficacy of maternal multiple micronutrient (MMN)-fortified balanced-energy protein (BEP) and iron-folic acid (IFA) supplementation on newborn TL as a secondary outcome and mtDNAc as a non-declared outcome.DesignWe conducted a randomized controlled trial in rural Burkina Faso, among pregnant females (15-40 years old) enrolled at <21 weeks of gestation. Mothers received either MMN-fortified BEP and IFA (intervention) or IFA only (control) throughout pregnancy. Whole arterial blood samples were collected from the umbilical cord of 104 control and 90 intervention group infants, respectively. Average relative TL and mtDNAc were measured using quantitative polymerase chain reaction. Linear regression models were fitted to assess TL and mtDNAc differences across trial arms.ResultsWe found that a combined daily MMN-fortified BEP supplement and IFA tablet did not affect newborn TL [β = -0.010 (95% CI: -0.057, 0.036);P= 0.662] or mtDNAc [β = 0.065 (95% CI: -0.203, 0.073);P= 0.354], as compared to an IFA tablet alone. These findings were confirmed (P>0.05) by adjusting the regression models for potential prognostic factors of study outcomes at enrollment. Exploratory analyses indicated higher, but non-significantly different mtDNAc among children born either small-for-gestational age, low birthweight, or preterm.ConclusionsNewborns from mothers who received daily nutritional supplements across gestation did not have different relative TL or mtDNAc.
How side effects can improve treatment efficacy: a randomized trial
Authors: Schenk Lieven A. , Fadai Tahmine , Büchel Christian 
Published: November 2023

AbstractWhile treatment side effects may adversely impact patients, they could also potentially function as indicators for effective treatment. In this study, we investigated whether and how side effects can trigger positive treatment expectations and enhance treatment outcomes.In this preregistered trial (DRKS00026648), 77 healthy participants were made to believe that they will receive fentanyl nasal sprays before receiving thermal pain in a controlled experimental setting. However, nasal sprays did not contain fentanyl, rather they either contained capsaicin to induce a side effect (mild burning sensation) or saline (control). Following the initial phase, participants were randomized to two groups and underwent functional magnetic resonance imaging (fMRI). One group continued to believe that the nasal sprays could contain fentanyl while the other group was explicitly informed that no fentanyl was included. This allowed for the independent manipulation of the side effects and the expectation of pain relief.Our results revealed that nasal sprays with a side effect lead to lower pain than control nasal sprays without side effects. The influence of side effects on pain was dependent on individual beliefs about how side effects are related to treatment outcome, as well as on expectations about received treatment. FMRI data indicated an involvement of the descending pain modulatory system including the anterior cingulate cortex and the periaqueductal gray during pain after experiencing a nasal spray with side effects.In summary, our data show that mild side effects can serve as a signal for effective treatment thereby influencing treatment expectations and outcomes, which is mediated by the descending pain modulatory system. Using these mechanisms in clinical practice could provide an efficient way to optimize treatment outcome. In addition, our results indicate an important confound in clinical trials, where a treatment (with potential side effects) is compared to placebo.
AP-1 regulates heterogeneous cellular dormancy in TNBC
Authors: Dong Yang , Bai Jin , Fu Rong , Su Huilan , Wu Shan , Tang Dean G. , Zhou Jianjun 
Published: November 2023

AbstractDormant or slow cycling cells (SSCs) pre-exist in tumor and responsible for chemo-resistant and tumor recurrence. Label retaining is a common method to obtain live SCCs from tumor. Different label retaining methods have been developed, but there still haven’t been reported whether different label retaining methods would result in same or different population of SCCs. We have utilized three label retaining methods simultaneously and identified overlapping but non-identical subpopulations of SCCs. These SCCs have similar yet different phenotypes in cell cycle, detoxification, motility and most importantly chemo-resistance. Gene profile shows three subpopulations of SCCs share similar gene expression pattern, and AP-1 subunit JunB overexpression is a key regulator of cellular dormancy. Inhibition of AP-1 could reduce drug resistance and tumor recurrence caused by SCCs, makes it a potential drug target for SCC elimination that could Improve patients’ survival.
The physiological costs of spatial positioning and leadership in collective movements
Authors: Brandl H. B. , Klarevas-Irby J.A. , Zuniga D. , Wheat C. Hansen , Christensen C. , Omengo F. , Nzomo C. , Cherono W. , Nyaguthii B. , Farine D. R. 
Published: November 2023

ABSTRACTForming collectives can generate substantial benefits, but much less is known about the costs that individuals incur in doing so. We simultaneously captured individual movement, within-group position, leadership, and heart rate for each member in a group of wild vulturine guineafowl. Individuals had significantly increased heart rates when moving collectively, occupying more central positions within the group, or attempting to initiate directional movement when consensus among group members was low. Such cardiac system activation can be indicative of physiological stress, entailing increased energy expenditure and long-term physiological damage. Thus, individuals paid the highest physiological costs in situations where theory predicts the benefits of collective behaviours should be greatest, revealing a hidden trade-off of social living.
TheC. elegansMyc-family of transcription factors coordinate a dynamic adaptive response to dietary restriction
Authors: Cornwell Adam , Zhang Yun , Thondamal Manjunatha , Johnson David W. , Thakar Juilee , Samuelson Andrew V. 
Published: November 2023

AbstractDietary restriction (DR), the process of decreasing overall food consumption over an extended period of time, has been shown to increase longevity across evolutionarily diverse species and delay the onset of age-associated diseases in humans. InCaenorhabditis elegans, the Myc-family transcription factors (TFs) MXL-2 (Mlx) and MML-1 (MondoA/ChREBP), which function as obligate heterodimers, and PHA-4 (orthologous to forkhead box transcription factor A) are both necessary for the full physiological benefits of DR. However, the adaptive transcriptional response to DR and the role of MML-1::MXL-2 and PHA-4 remains elusive. We identified the transcriptional signature ofC. elegansDR, using theeat-2genetic model, and demonstrate broad changes in metabolic gene expression ineat-2DR animals, which requires bothmxl-2andpha-4. While the requirement for these factors in DR gene expression overlaps, we found many of the DR genes exhibit an opposing change in relative gene expression ineat-2;mxl-2animals compared to wild-type, which was not observed ineat-2animals withpha-4loss. We further show functional deficiencies of themxl-2loss in DR outside of lifespan, aseat-2;mxl-2animals exhibit substantially smaller brood sizes and lay a proportion of dead eggs, indicating that MML-1::MXL-2 has a role in maintaining the balance between resource allocation to the soma and to reproduction under conditions of chronic food scarcity. Whileeat-2animals do not show a significantly different metabolic rate compared to wild-type, we also find that loss ofmxl-2in DR does not affect the rate of oxygen consumption in young animals. The gene expression signature ofeat-2mutant animals is consistent with optimization of energy utilization and resource allocation, rather than induction of canonical gene expression changes associated with acute metabolic stress -such as induction of autophagy after TORC1 inhibition. Consistently,eat-2animals are not substantially resistant to stress, providing further support to the idea that chronic DR may benefit healthspan and lifespan through efficient use of limited resources rather than broad upregulation of stress responses, and also indicates that MML-1::MXL-2 and PHA-4 may have different roles in promotion of benefits in response to different pro-longevity stimuli.