bluuebunny/crossref_metadata_2025_split huggingface dataset:
Melatonin Alleviates Circadian Rhythm Disruption‐Induced Enhanced Luteinizing Hormone Pulse Frequency and Ovarian Dysfunction
Authors: Li Yujing , Pei Tianjiao , Zhu Huili , Wang Ruiying , Wu Lukanxuan , Huang Xin , Li Fangyuan , Qiao Xinyu , Zhong Yuchan , Huang Wei 
Published: January 2025

ABSTRACTCircadian rhythm disruption (CRD), stemming from sleep disorders and/or shift work, is a risk factor for reproductive dysfunction. CRD has been reported to disturb nocturnal melatonin signaling, which plays a crucial role in female reproduction as a circadian regulator and an antioxidant. The hypothalamic‐pituitary‐ovarian (HPO) axis regulates female reproduction, with luteinizing hormone (LH) pulse pattern playing a pivotal role in folliculogenesis and steroidogenesis. However, the effect of CRD on the HPO axis and the involvement of melatonin remains unclear. Female CBA/CaJ mice underwent CRD modeling, which involves alternating between standard light conditions and an 8‐h advance schedule every 3 days for 8 weeks, whereas control mice were maintained under a standard 12:12‐h light/dark (LD) cycle. Subsequent measurements of diurnal melatonin levels, LH pulse patterns assessments via serial tail‐tip blood sampling and evaluations of ovarian function were conducted. CRD altered the circadian rhythms of wheel‐running activity and melatonin secretion in mice and led to an augmented LH pulse pattern, evidenced by increased LH pulse frequency, mean LH levels, and pituitary LH beta‐subunit (LHβ) expression, irregular estrous cycles, abnormal luteal function, altered endocrine function, and ovarian oxidative stress. Melatonin treatment (10 mg/kg/day for 4 weeks) significantly improved the HPO axis disorder in CRD mice, decreasing the enhanced LH pulse frequency and pituitary LHβ expression. These findings were further validated using an in vitro LβT2 cell perfusion model. Furthermore, melatonin restored ovarian function and scavenged reactive oxygen species, thereby preventing apoptosis and preserving ovarian function. This study offers new insights into the impact of CRD on the HPO axis and emphasizes the potential of melatonin supplementation in mitigating its effects on female reproduction.
Low socioeconomic status is an under‐recognised source of challenges in academia
Authors: Arbuckle K. , Bethell E. J. , Hawthorn D. J. , Hunt K. , Khera M. , Lewis Z. , Mitchell J. , Nicholl M. H. , Reynolds L. A. 
Published: January 2025

AbstractBarriers faced by underrepresented groups in academia have increasingly formed the basis of serious discussion, consideration, and policies, recently (in the UK) under the mantle of equality, diversity, and inclusivity (EDI). While such recognition has not solved the challenges encountered by, for instance, women and ethnic minorities, it has at least ensured that consideration of such issues is becoming a normal part of policy and practice. One underrepresented group in academia is low socioeconomic status (working class) backgrounds, a characteristic that intersects widely with other more commonly considered EDI groups. However, socioeconomic status is not a legally protected characteristic in the UK, which has resulted in it receiving less attention in terms of consideration of the barriers it imposes and possible mitigations needed. Moreover, unlike often more salient EDI characteristics such as gender and ethnicity, outward‐facing cues of socioeconomic status are less visible at a glance, although they are often detectable in more subtle or indirect ways. Coupled with the attempts many working‐class academics make to ‘mask’ cues of their background, this creates a situation whereby low socioeconomic status is a ‘hidden’ barrier that commonly remains unrecognised and unaddressed throughout much of academia. Here, we provide an overview of the challenges faced by working‐class academic scientists based partly on the literature, which is currently limited, and partly from the experiences of our diverse working‐class authorship team. In doing so, we hope to bring greater awareness of working‐class backgrounds to the table in EDI discussions, and we provide suggestions for future research on and mitigation of the challenges faced by academic scientists from low socioeconomic status backgrounds.
DNA Methylation Associates With Sex‐Specific Effects of Experimentally Increased Yolk Testosterone in Wild Nestlings
Authors: Sepers Bernice , Ruuskanen Suvi , van Mastrigt Tjomme , Mateman A. Christa , van Oers Kees 
Published: January 2025

ABSTRACTMaternal hormones can profoundly impact offspring physiology and behaviour in sex‐dependent ways. Yet little is known about the molecular mechanisms linking these maternal effects to offspring phenotypes. DNA methylation, an epigenetic mechanism, is suggested to facilitate maternal androgens' effects. To assess whether phenotypic changes induced by maternal androgens associate with DNA methylation changes, we experimentally manipulated yolk testosterone levels in wild great tit eggs (Parus major) and quantified phenotypic and DNA methylation changes in the hatched offspring. While we found no effect on the handing stress response, increased yolk testosterone levels decreased the begging probability, emphasised sex differences in fledging mass, and affected methylation at 763 CpG sites, but always in a sex‐specific way. These sites are associated with genes involved in growth, oxidative stress, and reproduction, suggesting sex‐specific trade‐offs to balance the costs and benefits of exposure to high yolk testosterone levels. Future studies should assess if these effects extend beyond the nestling stage and impact fitness.
Understanding the Relationship Between Changes to Federal Fiscal Policy and Near‐Term Real GDP Growth
Authors: Nelson Jaeger , Wilson Matthew 
Published: January 2025

AbstractWe introduce two measures which highlight the relationship between changes in federal fiscal policy and economic growth. First, we conduct a growth decomposition exercise to compute the short‐run direct effects of changes in policy on real GDP growth, which we call the Federal Fiscal Impulse (FFI). Second, we build on this measure to develop the Federal Fiscal Impulse Index (FFII) which interprets changes in the components of fiscal policy relative to the growth rate of real GDP over recent history. Finally, we project these measures through 2026 using CBO's June 2024 baseline and discuss the measures' benefits and limitations.
Superoxide dismutase 2 deficiency in mesenchymal stromal cells induces sympathetic denervation and functional impairment of brown adipose tissue
Authors: Urano Yuya , Mii Shinji , Asai Shun , Esaki Nobutoshi , Ando Ryota , Shiraki Yukihiro , Iida Tadashi , Kato Katsuhiro , Hori Mika , Hayashi Yoshitaka , Shimizu Takahiko , Enomoto Atsushi 
Published: January 2025

AbstractBrown adipose tissue (BAT) is an energy‐consuming organ, and its functional dysregulation contributes to the development of metabolic diseases and obesity. BAT function is regulated by the sympathetic nervous system but declines with age, which is partly caused by reduced sympathetic nerve fibers innervating BAT. Thus far, the role of mesenchymal stromal/stem cells in age‐related BAT dysfunction remains unknown. Here, we show that BAT dysfunction may be induced by a defect in the antioxidant capacity of stromal cells that localize in and around the nerve fibers (perineurial cells) of BAT. These cells express Meflin, a marker of mesenchymal stromal/stem cells. Specific deletion of the antioxidant enzyme superoxide dismutase 2 in Meflin‐lineage cells caused sympathetic denervation and whitening of BAT and its functional impairment, as exemplified by a decline in the fat oxidation rate during the daytime. This phenotype was accompanied by overexpression of the neurorepulsive factor semaphorin 3A in perineurial cells. Notably, Meflin‐deficient mice exhibited resistance to doxorubicin‐induced BAT dysfunction. These results highlight the role of Meflin+ stromal cells, including perineurial cells, in maintaining BAT function and suggest that targeting BAT stromal cells provides a new avenue for improving BAT function.
Influence of Active Production Versus Passive Consumption of Podcasts on Medical Students' Learning Outcomes
Authors: Laupichler Matthias Carl , Aster Alexandra , Soyubey Lara , Masala Gilda , Winkelhorst Greta , Remmert Rike , Raupach Tobias , Peters Anthea 
Published: January 2025

ABSTRACTIntroductionIn recent years, podcasts have been increasingly deployed in medical education. However, studies often fail to evaluate the learning outcomes from these podcasts effectively. The aim of this study was to determine whether the active production of podcasts enhances students' knowledge compared to the passive consumption of student‐produced podcasts, as it increases the engagement with the learning content through active learning.MethodsThe study was conducted at a German medical school during the fifth‐year paediatrics block internship. The final sample consisted of 86 students who were divided into small groups that produced podcasts on one paediatric topic on the first day and listened to a podcast on another topic on the second day.ResultsThe first group, which produced a podcast on topic A and only listened to a podcast on topic B, performed significantly better on questions on topic A than on questions on topic B, (p < 0.01, d = 0.63). This effect was not observed in the second group, which produced a podcast on topic B and listened to a podcast on topic A (p = 0.81, d = 0.04). Additionally, it was found that a longer time interval between podcast production and the knowledge test led to poorer memory performance (β = 1.10, p = 0.04).ConclusionWhile the differing results between the two groups may be due to a lack of power to detect meaningful differences, this study nonetheless provides initial evidence that the active production of podcasts may enhance the learning outcomes of medical students.Trial Registration: Not applicable
Quantification of intraepithelial canine melanocytes in different somatic areas
Authors: Porcellato Ilaria , Lo Giudice Adriana , Sforna Monica , Giglia Giuseppe , Orlandi Margherita , Mechelli Luca , Brachelente Chiara 
Published: January 2025

AbstractBackgroundIn humans, the presence of an even distribution of melanocytes within the epidermal basal layer allows for uniform pigmentation in healthy and young individuals. Moreover, despite high variability in skin colours and tones, interindividual melanocyte density variability is low. However, dogs display a high intraindividual pigmentary variability in different anatomical areas.Hypothesis/ObjectiveData on canine melanocytes, including their distribution and density, are limited. This study aimed to assess melanocyte density across different anatomical areas in dogs of various breeds.Materials and MethodsSamples were harvested postmortem from 22 dogs of different breeds and ages. Samples were collected from the following: haired skin (back, ventral abdomen, head and pinnae), oral and conjunctival mucocutaneous junctions, oral mucosa (buccal mucosa, gingiva, palate) and nose. Immunohistochemical investigation using a cocktail containing Melan‐A and SOX‐10 antibodies was performed to evaluate the melanocytes:keratinocytes ratio (M:K ratio).ResultsVariable melanocyte density was recorded in different anatomical areas, with a higher M:K ratio on the eyelid (median: 1:4; interquartile range [IQR]: 1:3.8–1:5.1) and on the nose (median: 1:6.5; IQR: 1:5.2–1:9.6). Lower ratios were observed on the haired skin, particularly on the head (median: 1:113.6; IQR: 1:37.8–1:255.1).Conclusions and Clinical RelevanceTogether with different melanocyte densities in different anatomical areas, dogs showed a high interindividual variability, particularly on haired skin. This finding could be associated with colour phenotype, sun exposure, and breed. Variable densities of melanocytes also might justify different incidence of melanocytic tumours in hyperpigmented breeds and in different somatic areas, as well as provide an increased protective effect in chronically sun‐exposed areas.
On the long‐time behavior of solutions to the Navier–Stokes–Fourier system on unbounded domains
Authors: Chiodaroli Elisabetta , Feireisl Eduard 
Published: January 2025

AbstractWe consider the Navier–Stokes–Fourier (NSF) system on an unbounded domain in the Euclidean space , supplemented by the far‐field conditions for the phase variables, specifically: as . We study the long‐time behavior of solutions and we prove that any global‐in‐time weak solution to the NSF system approaches the equilibrium in the sense of ergodic averages for time tending to infinity. As a consequence of the convergence result combined with the total mass conservation, we can show that the total momentum of global‐in‐time weak solutions is never globally conserved.
Cytoreductive surgery and HIPEC with oxaliplatin for the treatment of peritoneal carcinomatosis from recurrent fibrolamellar carcinoma
Authors: Ballelli Luca , Vicente Emilio , Quijano Yolanda , Ferri Valentina 
Published: January 2025

Fibrolamellar hepatocellular carcinoma (FHCC) is a rare variant of hepatocellular carcinoma (HCC), characterised by a poorer prognosis in later stages compared with conventional HCC due to a high rate of local recurrence, lymph node metastasis and peritoneal metastasis. Conventional chemotherapy is generally ineffective, making surgery the only potentially curative treatment. Currently, surgery is also indicated in cases of recurrence, always aiming for an R0 resection.We present the case of a young patient with peritoneal and retroperitoneal carcinomatosis following multiple resections, exhibiting a peculiar ‘sarcomatoid’ pattern of recurrence that is primarily local and not widespread within the abdomen. Immunotherapy was ineffective, and after the third recurrence, a cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy was performed.To date, there are no studies on the effectiveness of intraperitoneal chemotherapy in FHCC, though promising results have been observed for conventional HCC. As reported in two other articles in the literature, we attempted to apply this approach to FHCC.
Study protocol for a Prospective Observational study of Safety Threats and Adverse events in Trauma (PrO-STAT): a pilot study at a level-1 trauma centre in Canada
Authors: Nazir Anisa , McGowan Melissa , Shore Eliane M , Keown-Stoneman Charles , Grantcharov Teodor , Nolan Brodie 
Published: January 2025

IntroductionTraumatic injuries are a significant public health concern globally, resulting in substantial mortality, hospitalisation and healthcare burden. Despite the establishment of specialised trauma centres, there remains considerable variability in trauma-care practices and outcomes, particularly in the initial phase of trauma resuscitation in the trauma bay. This stage is prone to preventable errors leading to adverse events (AEs) that can impact patient outcomes. Prior studies have identified common causes of these errors, including delayed diagnostics, disorganisation of staff, equipment issues and communication breakdowns, which collectively contribute to AEs. This study addresses gaps in understanding the root causes of these errors by evaluating the most frequent AEs in trauma care through real-time video reviews of resuscitations in the trauma bay. Insights from this evaluation will inform targeted interventions to improve procedural adherence, communication and overall team performance, ultimately reducing preventable errors and improving patient safety.Methods and analysisA prospective observational study will be conducted at St. Michael’s Hospital, a level-1 trauma centre, to evaluate resuscitations in the trauma bay. All consecutive trauma team activations over 12 months will be included, with data collected using audio-visual recordings and physiological monitoring. A synchronised data capture and analysis platform will comprehensively assess AEs, errors and human and environmental factors during trauma resuscitations. The study aims to detect recurring error patterns, evaluate practice variations and correlate trauma team performance with in-hospital outcomes. Statistical analyses will include descriptive statistics, logistic regression models and multivariable analyses to identify associations and predictors of AEs and patient outcomes.Ethics and disseminationInstitutional research ethics approval was obtained (SMH REB # 21-009). A modified consent model will be employed for participants. Staff, physicians and learners will be provided with information regarding the study and will have the option to opt-out or withdraw consent. Similarly, trauma patients and their next of kin will be informed about the study, with provisions for opting out or withdrawing consent within 48 hours of recording. Measures will be implemented to ensure data confidentiality, anonymity and respect for participants’ autonomy and privacy. The study results will be shared through peer-reviewed journal publications and conference presentations, and key institutional stakeholders will be informed about developing strategies to improve patient safety in trauma care.
Targeting Siglec-E facilitates tumor vaccine-induced antitumor immunity in renal carcinoma
Authors: Zheng Yanyan , Wang Jiawei , Zhao Guangya , Zhang Zichun , Shao Yingxiang , Lu Bowen , Zhang Yuchen , Chen Renjin , Sun Li , Xie Xiaohui , Ding Jiage , Zheng Junnian , Chai Dafei 
Published: January 2025

BackgroundSiglec-E is an immune checkpoint inhibitory molecule. Expression of Siglec-E on the immune cells has been shown to promote tumor regression. This study aimed to develop an adenovirus (Ad) vaccine targeting Siglec-E and carbonic anhydrase IX (CAIX) (Ad-Siglec-E/CAIX) and to evaluate its potential antitumor effects in several preclinical renal cancer models.MethodsAd vaccines encoding Siglec-E or CAIX were developed and evaluated for their therapeutic potential in mouse subcutaneous, lung metastatic, and orthotopic tumor models. The expression of Ad-Siglec-E/CAIX was confirmed via PCR and flow cytometry. Immune responses induced by Ad-Siglec-E/CAIX were assessed in vitro and in vivo using flow cytometry, immunohistochemistry, ELISA, histological analysis, cell proliferation, enzyme-linked immunosorbent spot, cytotoxic T lymphocytes (CTL) killing, and cell depletion assays.ResultsAd-Siglec-E/CAIX vaccine induced the increase of tumor-infiltrated immune cells, and significantly suppressed the subcutaneous tumor growth of renal carcinoma. Immunization with Ad-Siglec-E/CAIX promoted the induction and maturation of CD11c+dendritic cells and their subsets, which in turn enhanced tumor-specific CD8+T cell immune responses, as evidenced by increased CD8+T cell proliferation and CTL activity. Importantly, the deletion of CD8+T cells in vivo abolished the antitumor effect of the Ad-Siglec-E/CAIX vaccine, highlighting the essential role of functional CD8+T cell responses. The potent therapeutic efficacy of the Ad-Siglec-E/CAIX vaccine was also observed in lung metastasis and orthotopic tumor models through tumor-specific CD8+T cell immune responses.ConclusionsOur results indicate that targeting Siglec-E enhances the therapeutic efficacy of Ad-CAIX against renal carcinoma, providing a promising therapeutic option for solid tumors.
Acute kidney injury recovery status predicts mortality and cardiorenal outcomes in patients admitted with acute decompensated heart failure
Authors: Barua Sumita , Chavali Sanjay , Vien Albert , Mahendran Shehane , Makarious David , Lo Phillip , Pringle Kirsty , Chong James , Muthiah Kavitha , Hayward Christopher 
Published: January 2025

BackgroundAcute kidney injury (AKI) in the context of acute decompensated heart failure (ADHF) encompasses a broad spectrum of phenotypes with associated disparate outcomes. We evaluate the impact of ‘ongoing AKI’ on prognosis and cardiorenal outcomes and describe predictors of ‘ongoing AKI’.MethodsA prospective multicentre observational study of patients admitted with ADHF requiring intravenous furosemide was completed, with urinary angiotensinogen (uAGT) measured at baseline. AKI was defined using Kidney Disease Improving Global Outcomes (KDIGO) AKI criteria. AKI recovery status was defined as ‘no AKI’, ‘recovered AKI’ or ‘ongoing AKI’ based on renal function at hospital discharge. Event-free survival analysis was performed to predict death and cardiorenal outcomes at hospital discharge and 6-month follow-up. Multinomial logistic regression was performed to identify predictors of ongoing AKI. Multiclass receiver operator curve analysis was performed to evaluate the relationship between renin-angiotensin system (RAS) blockers and uAGT in predicting ongoing AKI.ResultsAmong 271 enrolled patients, 121 (44.6%) patients developed AKI, of whom 62 patients had ongoing AKI. Ongoing AKI was associated with increased risk of death (HR 6.89, p<0.001), in-hospital end-stage kidney disease (HR 44.39, p<0.001), 6-month composite of death, transplant, left ventricular assist device and heart failure hospitalisation (HR 3.09, p<0.001), and 6-month composite major adverse kidney events (HR 5.71, p<0.001). Elevated baseline uAGT levels, chronic beta-blocker and thiazide diuretic therapy, and lack of RAS blocker prescription at recruitment were associated with ongoing AKI. While uAGT levels were lower with RAS blocker prescription, in patients with ongoing AKI, uAGT levels were elevated regardless of RAS blocker status.ConclusionPatients experiencing ongoing AKI during ADHF admission were at increased risk of death and other adverse cardiorenal outcomes. Differential uAGT response in patients receiving RAS blockers with ongoing AKI suggests biomarkers may be helpful in predicting treatment responses and cardiorenal outcomes.