bluuebunny/crossref_metadata_2025_split huggingface dataset:
H3K27ac acts as a molecular switch for doxorubicin-induced activation of cardiotoxic genes
Authors: Hong Yu , Li Xinlan , Li Jia , He Qiuyi , Huang Manbing , Tang Yubo , Chen Xiao , Chen Jie , Tang Ke-Jing , Wei Chao 
Published: July 2024

Abstract
Background
Doxorubicin (Dox) is an effective chemotherapeutic drug for various cancers, but its clinical application is limited by severe cardiotoxicity. Dox treatment can transcriptionally activate multiple cardiotoxicity-associated genes in cardiomyocytes, the mechanisms underlying this global gene activation remain poorly understood.

Methods and results
Herein, we integrated data from animal models, CUT&Tag and RNA-seq after Dox treatment, and discovered that the level of H3K27ac (a histone modification associated with gene activation) significantly increased in cardiomyocytes following Dox treatment. C646, an inhibitor of histone acetyltransferase, reversed Dox-induced H3K27ac accumulation in cardiomyocytes, which subsequently prevented the increase of Dox-induced DNA damage and apoptosis. Furthermore, C646 alleviated cardiac dysfunction in Dox-treated mice by restoring ejection fraction and reversing fractional shortening percentages. Additionally, Dox treatment increased H3K27ac deposition at the promoters of multiple cardiotoxic genes including Bax, Fas and Bnip3, resulting in their up-regulation. Moreover, the deposition of H3K27ac at cardiotoxicity-related genes exhibited a broad feature across the genome. Based on the deposition of H3K27ac and mRNA expression levels, several potential genes that might contribute to Dox-induced cardiotoxicity were predicted. Finally, the up-regulation of H3K27ac-regulated cardiotoxic genes upon Dox treatment is conservative across species.

Conclusions
Taken together, Dox-induced epigenetic modification, specifically H3K27ac, acts as a molecular switch for the activation of robust cardiotoxicity-related genes, leading to cardiomyocyte death and cardiac dysfunction. These findings provide new insights into the relationship between Dox-induced cardiotoxicity and epigenetic regulation, and identify H3K27ac as a potential target for the prevention and treatment of Dox-induced cardiotoxicity.
Dexmedetomidine as a total intravenous anesthetic in pediatric patients undergoing cleft lip and palate surgery: a case series
Authors: Yahya Corry Quando , Andriyanto Lucky , Priyadi Yantoko Azis 
Published: July 2024

Abstract
Background
Surgery for pediatric cleft lip and palate repair often utilizes high-dose opioids and inhaled anesthesia, thereby causing postoperative complications such as desaturation and/or severe agitation after anesthesia. These complications are detrimental to the child and medical personnel and cause tremendous psychologic stress to parents. Our aim is to decrease these complications through dexmedetomidine, an alpha-2 receptor agonist with anxiolytic, sympatholytic, and analgetic properties. Devoid of respiratory depressant effect, it allows patients to maintain effective ventilation and reduce agitation, postoperatively. Its unique anesthetic property may shed light on providing safe anesthesia and gentle emergence to this young, vulnerable population.

Case presentation
A total of 21 patients of Sundanese ethnicity, aged 3 months to 8 years (9 males and 12 females), underwent cleft lip or cleft palate surgery using total intravenous dexmedetomidine. Anesthesia was induced using sevoflurane, fentanyl, and propofol, and airway was secured. Intravenous dexmedetomidine 1.5 μg/kg was administered within 10 minutes, and a maintenance dose of 1.5 μg/kg/hour was continued as the sole anesthetic maintenance agent thereafter. Hemodynamics and anesthetic depth using Patient State Index (SEDLine™ monitor, Masimo Corporation, Irvine, CA, USA) were monitored carefully throughout the surgical procedure. Dexmedetomidine did not cause any hemodynamic derangements or postoperative complications in any of our patients. We found agitation in 9.5% (2/21) of patients.

Conclusion
Dexmedetomidine can be used as a total intravenous anesthetic agent to maintain anesthesia and provide gentle emergence to infants and young children undergoing cleft lip and palate repair.
Establishment and validation of a risk prediction model for delayed neurocognitive recovery associated with cerebral oxygen saturation monitoring
Authors: Luo Ning , Gao Xiaowei , Ye Chunyan , Wang Lu , Tang Lu , Xie Yongqiu , Wang E. 
Published: July 2024

Abstract
Background
Delayed neurocognitive recovery (DNR) is a common complication in patients undergoing laparoscopic surgery, and there are currently no effective therapies. It is vital to provide a reliable basis for clinical prediction. This study tried to analyse the risk factors for DNR in patients undergoing laparoscopic colorectal surgery and to establish a risk prediction model.

Methods
A retrospective analysis of the clinical data and DNR status of patients undergoing laparoscopic colorectal surgery at Xiangya Hospital of Central South University from March 2018 to July 2020 was conducted. Logistic regression was performed to analyse the related risk factors for DNR post-operatively, and the predictive model of DNR post-operatively was constructed and validated internally. Patients who underwent laparoscopic colorectal surgery between January and July 2021 were also selected for external validation of the predictive model, to ultimately investigate the risk factors for DNR in patients undergoing laparoscopic colorectal surgery.

Results
The incidence of DNR in patients undergoing laparoscopic colorectal surgery was 15.2% (31/204). The maximum variability of cerebral oxygen, age, education, and pre-existing diabetes was related to the incidence of DNR (p < 0.05). The risk prediction model of DNR after laparoscopic colorectal surgery was established. The internal and external validation showed that the discrimination was good (the AUCs were 0.751 and 0.694, respectively).

Conclusions
The risk prediction model of DNR related to cerebral oxygen saturation monitoring shows good predictive performance and clinical value, providing a basis for postoperative DNR prevention.
Cultural rice fields in the wave of climate change: a multilateral evolutionary game framework for adaptive management of agricultural heritage systems
Authors: Yusheng Chen , Zhaofa Sun , Yongwei Zhou 
Published: July 2024

Abstract
Agricultural Heritage Systems (AHS) are pivotal in preserving rich agricultural production experience and traditional culture, as well as in maintaining biodiversity and promoting sustainable development in agriculture and rural economies. However, climate change poses significant threats to these systems, such as ecological degradation, biodiversity loss, and shifts in agricultural production patterns. This study, grounded in theories of information asymmetry and bounded rationality, constructs evolutionary game models for adaptive management of AHS under market mechanisms and government guidance. By employing stability analysis and numerical simulation with Delay Differential Equations (DDE) that consider historical delays, and through sensitivity analysis, this research delves into the strategic evolutionary outcomes of stakeholders under various scenarios. It aims to provide theoretical insights and policy recommendations for the dynamic protection and adaptive management of AHS in the face of climate change. The findings indicate that the public goods nature of AHS, alongside externalities and information asymmetry, leads to market failure. Sole reliance on autonomous actions by farmers and meteorological departments is insufficient for optimal resource allocation and effective protection. Government intervention, through regulatory and incentive measures, can effectively mitigate market failures and steer adaptive management of AHS towards efficiency and sustainability. Moreover, the study identifies key factors for adaptive management, such as enhancing stakeholders’ initial willingness to participate, reducing the costs of adapting to climate change, optimizing cooperative benefit distribution mechanisms, and increasing the profitability of resource cooperation. Sensitivity analysis of government subsidies and penalty mechanisms further reveals the complex and critical role these policy tools play in fostering stakeholder engagement. Based on these findings, the study recommends enhancing initial participation willingness, controlling transformation costs to alleviate economic burdens, optimizing benefit distribution mechanisms to boost cooperative resource profitability, and establishing dynamic subsidy and penalty mechanisms for optimal resource allocation. The theoretical and practical contributions of this research lie in applying theories of information asymmetry and bounded rationality to the adaptive management of AHS under climate change, enriching the theoretical framework in this field, and providing scientific decision-making support for policymakers. By demonstrating an effective path for AHS protection through combined government and market mechanisms in the context of global climate change, this research holds significant theoretical and practical implications for enhancing the efficiency of adaptive management of AHS, protecting, and inheriting valuable agricultural cultural heritage.
Unveiling a novel memory center in human brain: neurochemical identification of the nucleus incertus, a key pontine locus implicated in stress and neuropathology
Authors: de Ávila Camila , Gugula Anna , Trenk Aleksandra , Intorcia Anthony J. , Suazo Crystal , Nolz Jennifer , Plamondon Julie , Khatri Divyanshi , Tallant Lauren , Caron Alexandre , Blasiak Anna , Serrano Geidy E. , Beach Thomas G. , Gundlach Andrew L. , Mastroeni Diego F. 
Published: July 2024

Abstract
Background
The nucleus incertus (NI) was originally described by Streeter in 1903, as a midline region in the floor of the fourth ventricle of the human brain with an ‘unknown’ function. More than a century later, the neuroanatomy of the NI has been described in lower vertebrates, but not in humans. Therefore, we examined the neurochemical anatomy of the human NI using markers, including the neuropeptide, relaxin-3 (RLN3), and began to explore the distribution of the NI-related RLN3 innervation of the hippocampus.

Methods
Histochemical staining of serial, coronal sections of control human postmortem pons was conducted to reveal the presence of the NI by detection of immunoreactivity (IR) for the neuronal markers, microtubule-associated protein-2 (MAP2), glutamic acid dehydrogenase (GAD)-65/67 and corticotrophin-releasing hormone receptor 1 (CRHR1), and RLN3, which is highly expressed in NI neurons in diverse species. RLN3 and vesicular GABA transporter 1 (vGAT1) mRNA were detected by fluorescent in situ hybridization. Pons sections containing the NI from an AD case were immunostained for phosphorylated-tau, to explore potential relevance to neurodegenerative diseases. Lastly, sections of the human hippocampus were stained to detect RLN3-IR and somatostatin (SST)-IR.

Results
In the dorsal, anterior-medial region of the human pons, neurons containing RLN3- and MAP2-IR, and RLN3/vGAT1 mRNA-positive neurons were observed in an anatomical pattern consistent with that of the NI in other species. GAD65/67- and CRHR1-immunopositive neurons were also detected within this area. Furthermore, RLN3- and AT8-IR were co-localized within NI neurons of an AD subject. Lastly, RLN3-IR was detected in neurons within the CA1, CA2, CA3 and DG areas of the hippocampus, in the absence of RLN3 mRNA. In the DG, RLN3- and SST-IR were co-localized in a small population of neurons.

Conclusions
Aspects of the anatomy of the human NI are shared across species, including a population of stress-responsive, RLN3-expressing neurons and a RLN3 innervation of the hippocampus. Accumulation of phosphorylated-tau in the NI suggests its possible involvement in AD pathology. Further characterization of the neurochemistry of the human NI will increase our understanding of its functional role in health and disease.

Graphical Abstract
Opportunities and challenges of smart technology for small independent fashion retailers: a reflexive thematic analysis using the technology-organization-environment framework
Authors: Chang Hyo Jung , Bruess Francine , Chong Jo Woon 
Published: July 2024

AbstractSmart technology has become an increasingly prominent feature in the fashion apparel industry. However, small retailers still face challenges while trying to adopt such innovative smart technologies to increase consumer interaction and sales. By applying the Technology, Organization, and Environment (TOE) framework, the aim of this study is to understand small independent fashion retail owners’ and employees’ thoughts on innovative retail technologies and their reactions to the currently available new technology. A qualitative research method of in-depth interviews with 11 participants working in fashion companies was used. The themes that emerged in this study represent criteria to be met prior to adopting new technology for small fashion retailers, including transparency, consistency, and integration of technology. While there were concerns regarding the cost and timing of adopting smart technology, they all expressed unanimous agreement that these advancements would become the next major trend in fashion retail, enhancing consumer connectivity. In particular, the smart technology they plan to adopt must possess the capability for reciprocity between consumers and the company. This will motivate a resurgence of innovative technologies in the less advanced fragment of small independent fashion retailers. Future research can focus on analyzing how the implementation of new smart technologies affects these types of businesses and their customer satisfaction.
Gender dynamics in humanitarian leadership: navigating COVID-19 and beyond
Authors: Bode Annika 
Published: July 2024

AbstractThis paper explores the intersection of the impacts of COVID-19 on women and girls in humanitarian settings with the necessity of incorporating female perspectives in decision-making roles within multilateral institutions delivering humanitarian aid. Women remain underrepresented in leadership positions in these multilateral institutions. However, increased female participation in leadership roles is linked to greater consideration of women’s needs in humanitarian response plans, thereby promoting gender-sensitive recovery efforts. Given COVID-19’s exacerbation of preexisting gender disparities in fragile settings, gender-responsive relief measures are crucial in humanitarian contexts. With the rising demand for humanitarian aid, prioritizing gender-sensitive and inclusive responses is essential for fostering an equitable and resilient post-COVID-19 future.
Decomposition of life expectancy differentials with (and without) conditions by educational attainment for major groups of causes in contemporary Spain: where is the advantage?
Authors: Bramajo Octavio , Zueras Pilar , Rentería Elisenda , Permanyer Iñaki 
Published: July 2024

Abstract
Introduction
Healthy life expectancy is higher among individuals with higher socioeconomic standing. However, it is unclear whether such advantage is attributable to longer (i.e., mortality advantage) or to healthier (morbidity advantage) lifespans across different health conditions.

Objective
Estimate the contribution of mortality and morbidity components in differences in condition-free life expectancies (CFLE) and life expectancy with conditions (LEWC) for five major groups of conditions by sex and educational attainment, instead of using a global indicator of morbidity.

Methods
Using the Sullivan Method, we computed remaining life expectancies at age 40 and 65, CFLE, and LEWC and applied a stepwise decomposition technique, using national health surveys along with mortality data, in a cross-sectional analysis.

Results
An educational gradient was present in almost all conditions, with different intensities. For females, morbidity was the main contributor to educational differences in health expectancies, but mainly in the older age groups. For males, the drivers behind higher health expectancies for high-educated males were evenly distributed across mortality and morbidity between ages 40 and 65, but after that, the mortality gradient vanished between high-educated and middle-educated individuals.

Discussion
The changing contribution of the mortality and morbidity gradient for different conditions across age-groups brings evidence to adequately plan health policies to mitigate health gaps and improve quality of life of the populations in a lower social standing.
The Effectiveness and Safety of Romosozumab and Teriparatide in Postmenopausal Women With Osteoporosis
Authors: Hartz Martin C , Johannessen Fabian B , Harsløf Torben , Langdahl Bente L 
Published: July 2024

Abstract

Purpose
The purpose of this observational study was to investigate the effectiveness and safety of romosozumab (ROMO) and teriparatide (TPTD) in a clinical setting.

Methods
A total of 315 postmenopausal women were included based on the reimbursement criteria for ROMO and TPTD at the Department of Endocrinology at Aarhus University Hospital. Criteria for ROMO were bone mineral density (BMD) T-score &lt; −2.5 (femoral neck [FN], total hip [TH], or lumbar spine [LS]) + a fragility fracture (hip, spine, pelvis, distal forearm, or proximal humerus) within 3 years. Criteria for TPTD: within 3 years, ≥ 2 vertebral fractures or 1 vertebral fracture + BMD T-score (FN, TH, or LS) &lt; −3. Data were collected from medical records. The primary end point was percentage change from baseline in BMD (FN, TH, and LS) at month 12. BMD was measured by dual-energy x-ray absorptiometry (DXA).

Results
At month 12, ROMO led to significantly (P &lt; .001) larger increases than TPTD in BMD (FN: 4.8% vs 0.2%, TH: 5.7% vs 0.3%, and LS: 13.7% vs 9.3%). Discontinuation rate was lower with ROMO than with TPTD. Lower incidence of cardiovascular adverse events was observed with ROMO compared to TPTD. Treatment-naïve patients had nonsignificantly higher BMD increases compared to previously treated patients with both ROMO and TPTD.

Conclusion
Treatment with ROMO yields larger increases in BMD than TPTD after 12 months and a higher rate of completion. ROMO was associated with a higher adherence.
Longitudinal Evaluation of Reproductive Endocrine Function in Men With ACTH-Dependent Cushing Syndrome
Authors: Shekhar Skand , McGlotten Raven N , Cutler Gordon B , Crowley Matthew J , Pieper Carl F , Nieman Lynnette K , Hall Janet E 
Published: July 2024

Abstract

Context
Hypogonadism may be caused by Cushing syndrome (CS) and may intensify its adverse consequences.

Objective
This work aimed to determine the frequency of male hypogonadism before and after curative surgery for CS, and its cause.

Methods
Post hoc analyses of prospective cohort studies were conducted at a clinical research center. Study participants were men with adrenocorticotropic hormone (ACTH)-dependent CS: cohort 1 (C1) (n = 8, age 32.5 ± 12 years; studied 1985-1989) and cohort 2 (C2) (n = 44, 42.7 ± 15.1 years; studied 1989-2021). Interventions included the following: C1: every 20-minute blood sampling for 24 hours before and 1 to 40 months after surgical cure. Three individuals underwent gonadotropin-releasing hormone (GnRH) stimulation tests pre and post surgery. C2: Hormone measurements at baseline and 6 and 12 months (M) post cure. Main outcome measures included the following: C1: LH, FSH, LH pulse frequency, and LH response to GnRH. C2: LH, FSH, testosterone (T), free T, free thyroxine, 3,5,3′-triiodothyronine, thyrotropin, and urine free cortisol (UFC) levels and frequency of hypogonadism pre and post surgery.

Results
C1: mean LH and LH pulse frequency increased after surgery (P &lt; .05) without changes in LH pulse amplitude, mean FSH, or peak gonadotropin response to GnRH. C2: 82% had baseline hypogonadism (total T 205 ± 28 ng/dL). Thyroid hormone levels varied inversely with UFC and cortisol. LH, total and free T, and sex hormone-binding globulin increased at 6 and 12 M post surgery, but hypogonadism persisted in 51% at 6 M and in 26% at 12 M.

Conclusion
Hypogonadism in men with CS is widely prevalent but reversible in approximately 75% of patients 1 year after surgical cure and appears to be mediated through suppression of hypothalamic GnRH secretion, and modulated by thyroid hormones.
Epigenetic Aging Helps Explain Differential Resilience in Older Adults
Authors: Klopack Eric T. , Crimmins Eileen M. 
Published: July 2024

Abstract
Past research suggests that resilience to health hazards increases with age, potentially because less resilient individuals die at earlier ages, leaving behind their more resilient peers. Using lifetime cigarette smoking as a model health hazard, we examined whether accelerated epigenetic aging (indicating differences in the speed of individuals’ underlying aging process) helps explain age-related resilience in a nationally representative sample of 3,783 older U.S. adults from the Health and Retirement Study. Results of mediation moderation analyses indicated that participants aged 86 or older showed a weaker association between lifetime cigarette smoking and mortality relative to participants aged 76–85 and a weaker association between smoking and multimorbidity relative to all younger cohorts. This moderation effect was mediated by a reduced association between smoking pack-years and epigenetic aging. This research helps identify subpopulations of particularly resilient individuals and identifies epigenetic aging as a potential mechanism explaining this process. Interventions in younger adults could utilize epigenetic aging estimates to identify the most vulnerable individuals and intervene before adverse health outcomes, such as chronic disease morbidity or mortality, manifest.
Extraordinary model systems for regeneration
Authors: Accorsi Alice , Guo Longhua , Marshall Wallace F. , Mommersteeg Mathilda T. M. , Nakajima Yu-ichiro 
Published: July 2024

ABSTRACT
Regeneration is the remarkable phenomenon through which an organism can regrow lost or damaged parts with fully functional replacements, including complex anatomical structures, such as limbs. In 2019, Development launched its ‘Model systems for regeneration’ collection, a series of articles introducing some of the most popular model organisms for studying regeneration in vivo. To expand this topic further, this Perspective conveys the voices of five expert biologists from the field of regenerative biology, each of whom showcases some less well-known, but equally extraordinary, species for studying regeneration.