bluuebunny/crossref_metadata_2025 huggingface dataset:
Dyadic Associations of Suicidal Risk Predicting Relationship Satisfaction in a Clinical Sample
Authors: Morgan Preston C. , Love Heather A. , Hunt Quintin A. , King Salena
Published: January 2025

This study investigated the prevalence of suicidal risk and associated trajectories of relational satisfaction in couples presenting for therapy using a national clinical data set, the Marriage and Family Therapy Practice Research Network (MFT‐PRN). The sample assessed 296 different‐sex couples attending couple therapy at sessions one, four, and eight. Nearly a quarter of couples indicated suicidal risk at session one. Dyadic latent growth models revealed that higher suicidal risk had a small but significant association with lower initial relationship satisfaction for men; thus, while the suicidal risk is associated with men's lower relationship satisfaction at intake, it may not continue to have impacts later in treatment. Alternative analyses of 27 same‐sex couples revealed a quarter of couples with suicidal risk at session one and that suicidal risk was not associated with relationship satisfaction. Although suicide risk was not associated with changes in relational satisfaction over time, suicidal risk should be assessed for couples presenting to therapy.
The Associations Between Adverse Childhood Experiences, Shared Religious/Spiritual Practices, and Relationship Satisfaction in Couple Therapy: Sessions 1 Through 6
Authors: Yoo Hana , Johnson Lee N. , Wagner Kaelie N. , Cherry Kyla A.
Published: January 2025

The present study utilized a sample of 374 distressed couples seeking therapy to investigate: (1) how partners' adverse childhood experiences (ACEs) and shared religious/spiritual (R/S) practices are associated with their relationship satisfaction at intake and (2) the rate and shape of change in relationship satisfaction over the first six sessions. The results from multilevel modeling (MLM) demonstrated that males' ACEs were negatively associated with both their own and their partners' relationship satisfaction at intake, whereas females' ACEs were negatively associated only with their own satisfaction, not their partners'. Regarding shared R/S practices, only females' reports were positively associated with both their own and their partners' satisfaction at intake; no effects were observed for males' reports. Lastly, changes in relationship satisfaction from sessions one through six were found to be curvilinear, with more rapid change occurring initially, followed by a slowdown as therapy progressed.
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

Circadian 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

Barriers 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

Maternal 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

We 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

Brown 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

Introduction

In 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.

Methods

The 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.

Results

The 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).

Conclusion

While 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

Background

In 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/Objective

Data 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 Methods

Samples 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).

Results

Variable 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 Relevance

Together 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.
Re-examining the origin and relationship of the Australian octoploid Euphorbia boöphthona using seed morphology
Authors: PARK Ki-Ryong
Published: January 2025

This study aimed to test previous hypotheses about the origin and relationships among the Australian octoploid Euphorbia boöphthona by studying seed morphological characters using scanning electron microscopy. The seed morphologies of the five Australian species of Euphorbia sect. Eremophyton are highly variable and heterogeneous, thus failing to support the previous hypothesis that they are a natural taxon. The diploids E. tannensis and E. parvicaruncula have similar seed shapes, sizes, and surface patterns, suggesting that they are closely related. Although the seed surface of the octoploid E. boöphthona (2n = 56) is uniquely mamillate, the papillae are well developed along the slits of mamilla, very similar to the seed surface of the hexaploid E. stevenii (2n = 42), which shows a distinct papillate pattern. These seed morphological characters support the hypothesis that E. stevenii may be an ancestor of E. boöphthona, as suggested by recent genetic studies.
On the long‐time behavior of solutions to the Navier–Stokes–Fourier system on unbounded domains
Authors: Chiodaroli Elisabetta , Feireisl Eduard
Published: January 2025

We 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.
Congestive myelopathy secondary to epidural venous engorgement and venous congestion in a patient with Budd-Chiari syndrome and its management through inferior vena cava stenting
Authors: Sahoo Biswajit , Panigrahi Manas Kumar , Gupta Shubham , Nayak Manoj Kumar
Published: January 2025

Budd-Chiari syndrome with obstruction in the inferior vena cava causes increased venous pressure in the azygous-hemiazygous system and paravertebral venous plexus, which is transmitted to the epidural venous plexus, devoid of the valves. It causes epidural venous plexus engorgement and venous congestion and may present rarely with low back pain or radiating pain. However, patients developing lower limb weakness as a complication of Budd-Chiari syndrome is an infrequent and severe presentation. Herein, we describe a case of Budd-Chiari syndrome with chronic inferior vena cava thrombosis in a patient in his 40s presenting with lower limb weakness, which improved after inferior vena cava stenting. In patients with back pain or lower limb weakness due to epidural venous engorgement and venous congestion, inferior vena cava occlusion secondary to Budd-Chiari syndrome should always be kept in mind, which can be treated successfully with endovascular stenting. Also, early intervention in Budd-Chiari syndrome can prevent permanent neurological deficits and the long-term complications of cirrhosis.
Precocious puberty: the unlikely herald of Familial adenomatous polyposis in a young girl
Authors: Karthik Vijayakumar , Jabbar Puthiyaveetil Khadar , Alam Ahmad , Nair Abilash
Published: January 2025

We describe the case of a girl in her middle childhood who presented with signs of heterosexual precocious puberty in the form of axillary and pubic hair growth, acne and clitoromegaly. Investigations showed elevated androgens and autonomous cortisol excess, suggesting an adrenal source. CT imaging confirmed a left adrenal mass and multiple colonic polyps. The family history of colonic polyps in her father, along with the presence of congenital hypertrophy of the retinal pigment epithelium and colonic polyps on colonoscopy, led to a diagnosis of familial adenomatous polyposis (FAP), subsequently confirmed by genetic testing. The patient underwent a successful adrenalectomy, with histopathology confirming an adrenocortical adenoma. Postsurgery, her hormonal levels normalised and symptoms improved. This case presents a unique combination of heterosexual precocious puberty caused by a cortisol and androgen co-secreting adrenal tumour in a girl with FAP, highlighting the complex interplay between endocrine disorders and genetic syndromes.
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

Introduction

Traumatic 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 analysis

A 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 dissemination

Institutional 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

Background

Siglec-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.

Methods

Ad 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.

Results

Ad-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.

Conclusions

Our 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

Background

Acute 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’.

Methods

A 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.

Results

Among 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.

Conclusion

Patients 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.
Multifaceted roles of MeCP2 in cellular regulation and phase separation: implications for neurodevelopmental disorders, depression, and oxidative stress
Authors: Good Katrina V. , Kalani Ladan , Vincent John B. , Ausió Juan
Published: January 2025

Methyl CpG binding protein 2 (MeCP2) is a chromatin-associated protein that remains enigmatic despite more than 30 years of research, primarily due to the ever-growing list of its molecular functions, and, consequently, its related pathologies. Loss of function MECP2 mutations cause the neurodevelopmental disorder Rett syndrome (RTT); in addition, dysregulation of MeCP2 expression and/ or function are involved in numerous other pathologies, but the mechanisms of MeCP2 regulation are unclear. Advancing technologies and burgeoning mechanistic theories assist our understanding of the complexity of MeCP2 but may inadvertently cloud it if not rigorously tested. Here, rather than focus on RTT, we examine relatively underexplored aspects of MeCP2, such as its dosage homeostasis at the gene and protein levels, its controversial participation in phase separation, and its overlooked role in depression and oxidative stress. All these factors may be essential to understanding the full scope of MeCP2 function in healthy and diseased states, but are relatively infrequently studied and require further criticism. The aim of this review is to discuss the esoteric facets of MeCP2 at the molecular and pathological levels and to consider to what extent they may be necessary for general MeCP2 function.
Limit Cycles of Discontinuous Planar Piecewise Systems Formed by Linear Centers and Linear Hamiltonian Systems Without Equilibria Separated by a Nonregular Line
Authors: Wang Min , Huang Lihong , Wang Jiafu
Published: January 2025

This paper is dedicated to studying the maximum number of crossing limit cycles of discontinuous planar piecewise-linear differential systems with three regions separated by a nonregular line and formed by linear centers and linear Hamiltonian systems without equilibria. There are two types of crossing limit cycles: one that intersects the nonregular line at three points and the other that intersects the nonregular line at four points, named three-point crossing limit cycles and four-point crossing limit cycles, respectively. We prove that the maximum numbers of three-point and four-point crossing limit cycles are three and one, respectively, and both reach their upper bounds. Furthermore, we show by concrete examples that one four-point crossing limit cycle and two three-point crossing limit cycles can exist simultaneously.
Artificial Intelligence Then and Now
Authors: Haigh Thomas
Published: January 2025

From engines of logic to engines of bullshit?
Can Graph Neural Networks be Adequately Explained? A Survey
Authors: Li Xuyan , Wang Jie , Yan Zheng
Published: January 2025

To address the barrier caused by the black-box nature of Deep Learning (DL) for practical deployment, eXplainable Artificial Intelligence (XAI) has emerged and is developing rapidly. While significant progress has been made in explanation techniques for DL models targeted to images and texts, research on explaining DL models for graph data is still in its infancy. As Graph Neural Networks (GNNs) have shown superiority over various network analysis tasks, their explainability has also gained attention from both academia and industry. However, despite the increasing number of GNN explanation methods, there is currently neither a fine-grained taxonomy of them, nor a holistic set of evaluation criteria for quantitative and qualitative evaluation. To fill this gap, we conduct a comprehensive survey on existing explanation methods of GNNs in this article. Specifically, we propose a novel four-dimensional taxonomy of GNN explanation methods and summarize evaluation criteria in terms of correctness, robustness, usability, understandability, and computational complexity. Based on the taxonomy and criteria, we thoroughly review the recent advances in GNN explanation methods and analyze their pros and cons. In the end, we identify a series of open issues and put forward future research directions to facilitate XAI research in the field of GNNs.
Visualizing Oxygen Distribution in the Along-the-channel Direction of Polymer Electrolyte Membrane Water Electrolyzers Using X-ray Imaging
Authors: Chang Hung-Ming J. , Firas Nausir Mahmoud , Lang Jack T. , Lopez Ochoa Jesus A. , Stansberry John M. , Parkinson Dilworth Y. , Karatay Elif , Danilovic Nemanja , Zenyuk Iryna V.
Published: January 2025

We developed an innovative operando X-ray computed tomography (CT) cell to elucidate oxygen content along a 10 cm x 1 cm membrane electrode assembly (MEA) of polymer electrolyte membrane water electrolyzer (PEMWE). The flow field consists of two parallel channels and one land. X-ray CT with an approximate 3 × 2 mm field of view and a 0.65 μm pixel size enabled visualization of the MEA and flow channels in operando PEMWEs. The cell incorporates three observation windows transparent to X-rays, strategically positioned near the inlet, in the middle of the flow channels, and at the outlet. 2D radiography was employed to observe oxygen content in the flow channels at various current densities with a time resolution step size of 5 ms. The use of water stained with NaI allowed observation of cell morphology and steady-state oxygen distribution in the porous transport layers (PTLs). Results indicate higher oxygen content in the PTL under the land compared to channel, indicating oxygen trapping. In both PTLs and channels higher oxygen content was observed at the outlet compared to the inlet. Oxygen was carried with water along the channel resulting in higher oxygen content at the outlet and this translated to higher content in the PTL due to lower water content in the channel near the outlet. A modeling study was conducted to support experimental results.
Tracking and Tackling the Capacity Fading in Viologen based Aqueous Organic Redox Flow Batteries
Authors: Mohapatra Sandeep Kumar , Ramanujam Kothandaraman , Sethuraman Sankararaman
Published: January 2025

Viologen-based redox flow batteries (RFBs) suffer from poor cycling in a neutral pH medium, especially at high concentrations, due to crossover and self-dimerization. In this study, a simple approach is proposed to reduce the permeability of active species by utilizing two pieces of NafionTM 212 membrane. To counter the capacity fade by self-dimerization of viologen, an unsymmetrical viologen derivative, 1-methyl-1′-(3-sulfonate) propyl-4,4′-bipyridinium iodide (MSPVI), is utilized in RFB. The effectiveness of this method is validated by successfully assembling a cell consisting of 1 M MSPVI paired with potassium ferrocyanide (K4[Fe(CN)6]). The cell demonstrates impressive longevity in cycle life with a capacity retention rate of 72.6% over 200 cycles. This suggests that the proposed suppression methods effectively mitigate the capacity fading in the viologen-based flow battery system.
Effectiveness and Safety of Dose‐Specific DOACs in Patients With Atrial Fibrillation: A Systematic Review and Network Meta‐Analysis
Authors: Oh Sang-Hyeon , Cheon Seunghyun , Choi Seo-Yong , Kim Young Seo , Choi Han-Gon , Chung Jee-Eun
Published: January 2025

Background: Dose adjustments of direct‐acting oral anticoagulants (DOACs) for atrial fibrillation are based on pivotal clinical trials assessing their effectiveness and safety in controlled settings. However, the appropriateness of these dosing strategies in real‐world practice is uncertain. The purpose of this study is to compare the effectiveness and safety of dose‐specific DOACs with those of warfarin.

Methods: This study retrieved articles from MEDLINE, Embase, and CENTRAL until March 5, 2024. Primary outcomes were the incidence of stroke/systemic embolisms (S/SEs) and major bleeding (MB). Direct pairwise meta‐analyses compared each dose‐specific DOAC with warfarin. Heterogeneity was assessed using Higgin’s I2 and Q statistics, while publication bias was evaluated through funnel plots and Begg’s and Egger’s tests, with adjusted pooled estimates calculated via trim‐and‐fill and precision‐effect estimate with standard error (PET‐PEESE) methods. A network analysis was conducted, with additional comparisons made using a Bayesian random‐effects model for indirect evidence.

Results: A total of 32 studies with 2,332,770 patients were included. Both standard‐dose (SD) and low‐dose (LD) DOACs significantly reduced S/SE, except for LD apixaban and LD edoxaban. Rivaroxaban did not show significant difference in MB compared to warfarin. In East Asian patients, all doses of DOACs exhibited lower hazard ratios (HRs) for S/SE and MB than those observed in the primary analysis, with LD rivaroxaban significantly reducing MB, a finding not observed in the primary analysis. Rank probability analysis indicated that the dose‐specific DOACs had different safety profiles and small but meaningful differences in effectiveness. SD apixaban (S/SE: second, MB: second) and edoxaban (S/SE: first, MB: fourth) and LD edoxaban (S/SE: fourth, MB: first) had high ranks. LD apixaban had the most significant difference in rank for S/SE from SD apixaban, ranking eighth compared to second.

Conclusions: This study found that all DOACs provided comparable or superior effectiveness and safety to warfarin. SD apixaban, SD edoxaban, and LD edoxaban achieved a favorable balance between preventing S/SE and MB risk.
Atypical Femur Fracture in a Teenager on Chronic Imatinib Therapy
Authors: Belzarena Ana C. , Cook James L.
Published: January 2025

Atypical femoral fractures (AFFs) are rare fractures usually associated with medications that can ultimately alter bone metabolism. Imatinib, a drug prescribed for treatment of chronic myeloid leukemia (CML), has been associated with altered bone homeostasis, however, with unknown clinical significance. Here, we present the case of a 17‐year‐old female, with a diagnosis of CML undergoing chronic imatinib therapy, who developed an AFF treated successfully with prophylactic fixation with intramedullary nailing. Our case underscores the importance of prompt recognition of this entity to allow patients timely appropriate care, even at an early age.
Comprehensive Analysis of FBXO43 Expression and Its Prognostic and Therapeutic Implications in Osteosarcoma
Authors: Jin Jiang , Yao Kang , Tingxiao Zhao , Longtao Yao , Yanlei Li , Jinlong Tian , Xiaojun Zhu , Liang Han
Published: January 2025

Background: Osteosarcoma (OS) is the most common malignant bone tumor in children and adolescents. FBXO43, a member of the F‐box protein family, has been identified as a crucial prognostic factor in several cancers. However, its role in osteosarcoma remains largely unexplored.

Methods: This study investigated the expression and potential role of FBXO43 across the TCGA pan‐cancer cohort, with a particular focus on sarcoma (SARC). We analyzed the relationship between FBXO43 expression and various cancer‐related pathways, immune infiltration, and genomic features, including TP53 mutations. We also conducted immunotherapy predictive analyses using TIDE and Submap algorithms. To validate our findings, we performed a series of in vitro experiments, including cell invasion and wound healing assays.

Results: FBXO43 was found to be significantly overexpressed in various cancers and was particularly associated with pathways such as E2F_TARGETS and G2M_CHECKPOINT in SARC samples. Differential FBXO43 expression was linked to distinct immune infiltration patterns and pathway enrichments. Notably, high FBXO43 expression in osteosarcoma was associated with a higher TP53 mutation rate. Predictive analyses indicated that patients with low FBXO43 expression had better immunotherapy responses, suggesting its potential as a diagnostic and prognostic biomarker. These findings were corroborated by our in vitro functional assays.

Conclusion: Our comprehensive analysis reveals that FBXO43 plays a critical role in the progression of osteosarcoma, impacting both immune infiltration and genomic stability. FBXO43 expression levels may serve as valuable biomarkers for predicting immunotherapy responses in osteosarcoma patients. Future studies should aim to elucidate the molecular mechanisms driving FBXO43’s role and validating these findings in clinical settings to develop targeted therapeutic strategies.
Heterogeneity Measures for Analyzing the Scale Effect and Anisotropy of Joint Roughness
Authors: Qin Jibo , Zhang Zhenhan , Ye Jun
Published: January 2025

Joint roughness of rock joints is one of the key factors influencing the mechanical properties of rock joints. The influence of joint roughness on the mechanical properties of rock mass is usually quantitatively characterized by joint roughness coefficient (JRC). The scale effect and the anisotropy of joint roughness are its important characteristics. The lack of a suitable heterogeneity measure for the scale effect and anisotropy of joint roughness makes it difficult to analyze its heterogeneity quantitatively. To solve this issue, this paper proposes the uniformity measure (normalized information entropy measure) and the nonuniformity measure (normalized information enthalpy measure) of a multivalued sequence based on the Shannon/probability entropy notion. Then, a heterogeneity measure of joint roughness is proposed, which realizes the quantitative characterization of the heterogeneity of the scale effect and anisotropy of joint roughness. Actual rock joint cases were used to collect JRC data with 10 sample sizes from 10 to 100 cm and 24 measurement directions from 0° to 345° and to calculate the heterogeneity measures of the joint roughness scale effect in 24 directions and joint roughness anisotropy in 10 sizes. The analysis results show the rationality and efficiency of the proposed measure. The proposed measure provides researchers and engineers with a reliable heterogeneity analysis tool for joint roughness scale effect and anisotropy.
A Broadband RCS Reduction Coating Using a Novel Arrangement of Metasurface Unit Cells Based on Two Substrates
Authors: Khalilzadeh M. , Ghafoorzadeh-Yazdi A. , Pezhman M. M.
Published: January 2025

In this paper, a new coating structure is proposed for broadband radar cross section (RCS) reduction using 1‐bit metasurfaces. The designed structure consists of two types of unit cell, arranged in concentric square rings. The substrate of unit cells is different, FR4 and Ultralum‐2000 with thicknesses of 2.4 and 0.762 mm, respectively. The proposed structure shows an ultrawideband property to reduce the RCS, less than −10 dB, in the frequency range of 14–45 GHz. This range covers part of Ku‐band (14–18 GHz), K‐band (18–27 GHz), and Ka‐band (27–40 GHz) and part of millimeter‐wave band (40–45 GHz). To validate the designed work and simulation results, a prototype with the dimension of 84 × 84 mm2 is fabricated and tested. Also, the RCS reduction is determined analytically and presented. The measured results verify well the analytical and simulation results. In short, this work includes three new points: (1) the use of two substrates with different thickness and dielectric constant to design unit cells, (2) a new arrangement of array cells in the form of concentric square rings, and (3) achieving a great bandwidth to reduce RCS.
Marijuana Poisoning in Canines in the Aburrá Valley (Antioquia‐Colombia), 2023‐2024
Authors: Marulanda Natalia Restrepo , Álvarez José Fernando Ortiz , Puerta Jaime Humberto Londoño , Peralta Angélica María Blandón , Corrales Natalia Uribe
Published: January 2025

Background and Aim: Marijuana poisoning in canines is still considered a taboo topic. Poisoning in pets is becoming increasingly common, in many cases resulting in severe clinical signs, such as ataxia, urinary incontinence, mydriasis, depression, and hyperesthesia. Colombia does not have any reliable test for the diagnosis of exposure to cannabis in animals, and it is not an obligation to report this kind of poisoning to the authorities. Therefore, the main objective of this study was to determine the frequency of cases compatible with tetrahydrocannabinoid (THC) poisoning in canines in the Aburrá valley (Antioquia‐Colombia), 2023‐2024.

Materials and Methods: A cross‐sectional study was conducted in the Aburrá valley (Antioquia‐Colombia) from 2023 to 2024. Veterinary centers that were allowed to participate were visited, and the clinical records were examined on the canines that were diagnosed positive for marijuana poisoning. We examined the clinical record for different risk factors that could explain the poisoning. A descriptive statistic and a Chi‐square test were used to identify risk factors; p < 0.05 were considered statistically significant.

Results: One hundred and thirteen (113) cases compatible with cannabis poisoning were found in dogs. Puppies, crossbreeds, trim sizes, and canines whose owners have middle or high economic incomes were the most affected. In addition, a relation between the route of possible cannabis poisoning and the severe presentation of clinical signs was found, with ingestion and inhalation being the routes that generated a more pronounced sign. Likewise, a relationship between age and the most probable route of exposure was found, finding that puppies were more related to the ingestion of cannabis products.

Conclusion: This is the first article in Colombia that was focused on determining the frequency of possible cannabis poisoning in canines. The dogs that are more susceptible to suffering cannabis poisoning are puppies and small‐size dogs that are attended by veterinary medical centers and are in neighborhoods that are recognizable by people who have high salaries.