bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reinforced subdomain-adversarial generalization network for multi-source fault diagnosis in industrial robotic joint reducers
Authors: Yan Qin , Xu Bin 
Published: February 2025

Abstract
To address the issue of reduced fault diagnosis accuracy for industrial robot joint reducers under unknown operating conditions, a multi-source domain adaptive fault diagnosis method based on a Reinforced Subdomain-Adversarial Adaptation Network (RSAAN) is proposed. This method effectively extracts domain-invariant features, enhancing the robustness of fault diagnosis under unfamiliar conditions. First, intrinsic distribution clustering is utilized to extract features that emphasize fault-specific differences while minimizing the influence of operating condition variations, thereby improving the generalizability of the domain-invariant features. Next, local adversarial training is introduced on top of global adversarial training to achieve better feature alignment when the distribution discrepancy between domain-invariant features and generalized source domain features is small. Finally, an adaptive adversarial factor is employed to adjust the weight balance between global and local adversarial training, enabling the model to extract and refine domain-invariant features from multiple source domains to adapt to various unseen operating conditions. The proposed method achieved over 95% diagnostic accuracy in multiple cross-domain diagnostic scenarios using publicly available gearbox and robot bearing datasets, demonstrating its effectiveness and reliability in diagnosing faults under unknown conditions. This approach provides critical technical support and decision-making guidance for fault diagnosis in industrial robots.
Reason beyond Proof
Authors: Dyck Corey W. 
Published: February 2025

Abstract
A central topic of debate in the aftermath of Wolff’s German Metaphysics was the principle of sufficient reason (PSR). While it might be tempting to divide the discussion into the Wolffian defenders of the principle and its anti-Wolffian detractors, things are not quite so straightforward. The significance of a proof of the PSR for Wolff himself has long been grossly exaggerated as Wolff’s attempts are not reflective of his distinctive philosophical rationalism. Moreover, even as Wolff’s most dogged opponents contested the unrestricted use of the principle in metaphysics, they accepted that the PSR held with respect to certain domains of beings. Moreover, Wolff’s critics went as far as to number the PSR among the highest principles of human cognition. Significantly, it is in its form as an undemonstrated and unlimited principle of cognition that the PSR serves Wolff’s critics as an indispensable foundation for their most distinctive doctrines.
easyEWAS: a flexible and user-friendly R package for Epigenome-Wide Association Study
Authors: Wang Yuting , Jiang Meijie , Niu Siyuan , Gao Xu 
Published: February 2025

Abstract

Motivation
Rapid advancements in high-throughput sequencing technologies especially the Illumina DNA methylation Beadchip greatly fueled the surge in epigenome-wide association study (EWAS), providing crucial insights into intrinsic DNA methylation modifications associated with environmental exposure, diseases, and health traits. However, current tools are complex and less user-friendly to accommodate appropriate EWAS designs and make downstream analyses and result interpretations complicated, especially for clinicians and public health professionals with limited bioinformatic skills.

Results
We integrated the current state-of-the-art EWAS analysis methods and tools to develop a flexible and user-friendly R package easyEWAS for conducting DNA methylation-based research using Illumina DNA methylation Beadchips. With easyEWAS, we provide a battery of statistical methods to support differential methylation position analysis across various scenarios, as well as differential methylation region analysis based on the DMRcate method. To facilitate result interpretation, we provide comprehensive functional annotation and result visualization functionalities. Additionally, a bootstrap-based internal validation was incorporated into easyEWAS to ensure the robustness of EWAS results. Evaluation in asthma patients as the example demonstrated that easyEWAS could simplify and streamline the conduction of EWAS and corresponding downstream analyses, thus effectively advancing DNA methylation research in public health and clinical settings.

Availability and implementation
easyEWAS is implemented as an R package and is available at https://github.com/ytwangZero/easyEWAS.
Disruption of recombination machinery alters the mutational landscape in plant organellar genomes
Authors: Waneka Gus , Broz Amanda K , Wold-McGimsey Forrest , Zou Yi , Wu Zhiqiang , Sloan Daniel B 
Published: February 2025

Abstract
Land plant organellar genomes have extremely low rates of point mutation yet also experience high rates of recombination and genome instability. Characterizing the molecular machinery responsible for these patterns is critical for understanding the evolution of these genomes. While much progress has been made toward understanding recombination activity in land plant organellar genomes, the relationship between recombination pathways and point mutation rates remains uncertain. The organellar-targeted mutS homolog MSH1 has previously been shown to suppress point mutations as well as non-allelic recombination between short repeats in Arabidopsis thaliana. We therefore implemented high-fidelity Duplex Sequencing to test if other genes that function in recombination and maintenance of genome stability also affect point mutation rates. We found small to moderate increases in the frequency of single nucleotide variants (SNVs) and indels in mitochondrial and/or plastid genomes of A. thaliana mutant lines lacking radA, recA1, or recA3. In contrast, osb2 and why2 mutants did not exhibit an increase in point mutations compared to wild-type (WT) controls. In addition, we analyzed the distribution of SNVs in previously generated Duplex Sequencing data from A. thaliana organellar genomes and found unexpected strand asymmetries and large effects of flanking nucleotides on mutation rates in WT plants and msh1 mutants. Finally, using long-read Oxford Nanopore sequencing, we characterized structural variants in organellar genomes of the mutant lines and show that different short repeat sequences become recombinationally active in different mutant backgrounds. Together, these complementary sequencing approaches shed light on how recombination may impact the extraordinarily low point mutation rates in plant organellar genomes.
Balancing Formal and Informal Caregiving Resources for Older Adults: The Role of Spatial Proximity of Family
Authors: Oh Gyeongrim , Lee Samsik 
Published: February 2025

Abstract

Objectives
To explore how informal and formal home care was balanced for older adults under the weakening informal caregiving systems due to sociodemographic changes in South Korea, this study examined the relationship between the two types of care and the effects of proximity to family caregivers on them.

Methods
We analyzed adults aged 65 years and older from the 7th wave of the Korean Longitudinal Study of Aging (KLoSA) (n = 722) with limitations in activities of daily living (ADL) or instrumental activities of daily living (IADL), or dementia. Multinomial logistic regression (MLR) was adopted to analyze the impact of family structure on the choice of informal caregivers. Two-stage least squares (2SLS), Heckman, and IV-Heckman models were applied to address endogeneity and sample selection biases.

Results
The results demonstrated that spouses and children close to older parents appeared to be primary caregivers. According to the IV-Heckman model, informal care substitutes for formal home care (b = -0.416, p &lt; .01), and both being married (b = 0.715, p &lt; .01) and proximity to children within one hour (b = 0.888, p &lt; .01) appeared to facilitate formal home care use.

Discussion
This study reveals that Informal and formal home care are inextricably linked. Spouses and adult children close to parents play a pivotal role in directly providing informal care and indirectly facilitating formal home care. Balancing informal/formal home care should be considered in medium- and long-term plans to improve older adults' well-being and reduce formal care's financial burden.
Sophorolipids from Starmerella bombicola: an alternative for treating skin lesions caused by herpes simplex virus type 1
Authors: Bigotto Briani Gisele , Dahmer Débora , Dyna André Luiz , Barboza Mario Gabriel Lopes , de Matos Ricardo Luis Nascimento , Baldo Cristiani , Bracarense Ana Paula Frederico Rodrigues Loureiro , Galhardi Ligia Carla Faccin , Lonni Audrey Alesandra Stinghen Garcia , Celligoi Maria Antonia Pedrine Colabone 
Published: February 2025

Abstract

Aims
This study aims to evaluate the antiviral activity of sophorolipids against herpes simplex virus type 1 (HSV-1) and develop an anti-herpetic formulation for treatment of cutaneous lesions caused by HSV-1.

Methods and results
The antiherpetic activity of sophorolipids was evaluated in vitro against both sensitive (KOS) and acyclovir-resistant HSV-1 strains. used as a model to assess the antiviral activity of sophorolipids against non-enveloped viruses Poliovirus was used as a model to assess the antiviral activity of sophorolipids against non-enveloped viruses. The results showed that sophorolipids exhibit effective antiviral activity against both strains with low cytotoxicity to VERO cells. However, antiviral activity against poliovirus was not observed, suggesting that sophorolipids specifically target enveloped virus. In vivo, the sophorolipid-based cream formulation demonstrated good stability and efficacy in reducing herpetic lesions, including those caused by the drug-resistant strain. Promising antiviral activity was confirmed through histopathological analysis, indicating a reduced occurrence of tissue damage in the treated group compared to the viral control.

Conclusions
Sophorolipids, whether isolated or incorporated as an active ingredient in a cream formulation, represent a promising and innovative alternative for the treatment of cutaneous lesions caused by HSV-1, including strains resistant to the reference drug.
Modelling the density and mass of the Milky Way’s proto-galaxy components with APOGEE-Gaia
Authors: Horta Danny , Schiavon Ricardo P 
Published: February 2025

ABSTRACT
Unravelling galaxy formation theory requires understanding galaxies both at high and low redshifts. A possible way to connect both realms is by studying the oldest stars in the Milky Way (i.e. the proto-Galaxy). We use the APOGEE-Gaia surveys to perform a purely chemical dissection of Milky Way (MW) stellar populations, and identify samples of stars likely belonging to proto-Galactic fragments. The metallicity dependence of the distribution of old MW stars in the [Mg/Mn]–[Al/Fe] enables the distinction of at least two populations in terms of their star formation histories: a rapidly evolved population likely associated with the main progenitor system of the proto-MW; and populations characterized by less efficient, slower, star formation. In the Solar neighbourhood less efficient star forming populations are dominated by the Gaia-Enceladus/Sausage accretion debris. In the inner Galaxy, they are largely associated with the Heracles structure. We model the density of chemically defined proto-Galaxy populations, finding that they are well represented by a Plummer model with a scale radius of $a\sim 3.5$ kpc, and an oblate ellipsoid with flattening parameters [$p\sim 0.8$; $q\sim 0.6$]; this finding indicates that the MW plausibly hosts a low-mass, metal-poor, bulge component. We integrate this density for chemically unevolved stars between $-2 \lt \mathrm{[Fe/H]} \lt -0.5$ to obtain a minimum stellar mass for the proto-Galaxy of $M_{*} (r\lt 10~\mathrm{kpc}) = 9.1\pm 0.2\times 10^{8}$ M$_{\odot }$. Our results suggest the proto-Milky Way is at least comprised of two significant fragments: the main in situ progenitor and the Heracles structure.
Targeting sickle cell pathobiology and pain with novel transdermal curcumin
Authors: Goel Yugal , Arellano Mya A , Fouda Raghda T , Garcia Natalie R , Lomeli Reina A , Kerr Daniel , Argueta Donovan A , Gupta Mihir , Velasco Graham J , Prince Richard , Banerjee Probal , Jana Sirsendu , Alayash Abdu I , Friedman Joel M , Gupta Kalpna 
Published: February 2025

Abstract
Several comorbidities of sickle cell disease (SCD) originate from red blood cell (RBC) instability, chronic inflammation, and oxidative stress. Development of scalable, cost-effective therapeutics suitable for chronic administration to prevent, attenuate, and perhaps reverse the consequences of RBC instability is needed. Curcumin has many of these attributes as a safe compound with antisickling, antiinflammatory, and antioxidant properties, but its translational potential has been constrained due to limited bioavailability from oral administration. The present study demonstrates the rapid and high bioavailability of a novel topical/transdermal (TD) curcumin gel formulation in the plasma and blood cells and its effectiveness in humanized sickle cell mice in: (i) ameliorating features of sickle cell pain hypersensitivity and axonal injury; (ii) reducing multiple manifestations of RBC instability including evidence of decreased hemolysis (reduced lactate dehydrogenase levels), enhanced RBC ATP levels along with decreased oxidative damage; (iii) decreasing multiple proinflammatory cytokines including interleukin-6, monocyte chemoattractant protein-1, granulocyte–macrophage colony-stimulating factor, and activation, normal T cell expressed and secreted protein in skin secretome; and (iv) reducing mast cell degranulation and activation. Our data suggest that an easy-to-use novel TD curcumin gel formulation has the potential to ameliorate chronic pain, improve RBC stability, and reduce inflammatory consequences of SCD.
Characterization of the Swi6/HP1 binding motif in its partner protein reveals the basis for the functional divergence of the HP1 family proteins in fission yeast
Authors: Oya Tomoyuki , Tanaka Mayo , Hayashi Aki , Yoshimura Yuriko , Nakamura Rinko , Arita Kyohei , Murakami Yota , Nakayama Jun‐ichi 
Published: February 2025

AbstractThe heterochromatin protein 1 (HP1) family recognizes lysine 9‐methylated histone H3 (H3K9me) and recruits other transacting factors to establish higher order chromatin structures. In the fission yeast Schizosaccharomyces pombe (S. pombe), two HP1 family proteins, Swi6 and Chp2, play distinct roles in recruiting transacting factors: Swi6 primarily recruits Epe1, a Jumonji C domain‐containing protein involved in histone H3K9 demethylation, whereas Chp2 recruits Mit1, a component of the Snf2/Hdac Repressive Complex. However, detailed mechanisms of how multiple HP1 family proteins and their respective interactors work cooperatively or exclusively to form higher order chromatin structures remain elusive. In this study, we investigated the interactions between Swi6 and Epe1. We found that Swi6 interacts with Epe1 through its chromoshadow domain, and identified a unique motif, named the FVI motif, in Epe1 involved in this interaction through detailed mapping of the region. Enhanced green fluorescent protein (EGFP) tethering assays showed that the FVI motif is sufficient to recruit ectopically expressed EGFP to heterochromatic regions, and mutational analyses revealed that conserved hydrophobic residues in this motif are essential for proper targeting. Structural simulations further supported the importance of these residues in Swi6 binding. Interestingly, Mit1 containing the Epe1 FVI motif was recruited to the heterochromatic regions by Swi6 but not by Chp2. Cells expressing mutant Mit1 maintained heterochromatic silencing even in chp2∆ cells, suggesting that Chp2 is not required for heterochromatin formation when Mit1 is recruited by Swi6. These findings highlight distinct HP1‐binding motifs in interactors, contributing to functional divergence among HP1 family proteins.
Current insights into anaesthesia and critical care management of patients with hepatocellular carcinoma
Authors: Monsel Antoine , Sitbon Alexandre , Roux Charles , Eyraud Daniel , Scatton Olivier , Vezinet Corinne , Oré Marie-Virginie , Gallet Jérémy , Wagner Mathilde , Thabut Dominique , Boughdad Sarah , Renaud Florence , Mazzola Alessandra , Goumard Claire , Allaire Manon ,   the Liver Institute of la Pitié-Salpêtrière (LIPS)—University Hospital in Paris
Published: February 2025

BACKGROUND
The incidence of hepatocellular carcinoma (HCC) is on the rise worldwide, due to the increasing prevalence of liver diseases associated with metabolic dysfunction and better management of cirrhosis and its complications. The diversification of HCC treatments has recently increased, with the choice of strategy based on HCC characteristics, liver function and comorbidities. The combination of new therapies has transformed the prognosis, with up to 70% survival at 5 years.

OBJECTIVE
The aim of this review was to analyse the most recent data on preoperative evaluation, peri-operative anaesthetic management of liver resection, liver transplantation and other types of procedures, and to highlight the multidisciplinary aspect of such management.

MAIN FINDINGS AND DISCUSSION
The importance of preanaesthetic evaluation will depend largely on the procedure proposed, associated co-morbidities and the stage of liver disease. This assessment should verify stabilisation of all comorbidities, and evaluate the degree of portal hypertension, cirrhosis severity and sarcopenia. Liver resection and liver transplantation for HCC present specific surgical challenges, and minimally invasive techniques improve recovery. Nonsurgical procedures considered as therapeutic (ablation) or standby (regional embolisation) are diverse, and all expose patients to specific intra-anaesthetic complications, sometimes requiring intensive care management. Peri-operative anaesthetic strategies deployed in the management of liver resection or nonsurgical procedures involve specific management of fluids, coagulation, narcosis and analgesia, which can impact on patients’ overall, and cancer prognosis. Lastly, new down-staging strategies combining several types of procedure and possibly immunotherapy, also call for collegial reflection on posthepatic transplant immunosuppression, which must remain tailored to each individual patient.
Eighteen-year analysis of anaesthetic management in Brugada syndrome
Authors: Borrell-Vega Jaume , Fernández Font José Daniel , Linares Miguel , Martínez-Pallí Graciela , Isabel-Roquero Alba , Mont Lluis , Brugada Josep , Arbelo Elena , Giménez-Milà Marc 
Published: February 2025

BACKGROUND
Brugada syndrome (BrS) is a genetic disorder that increases the risk of ventricular tachyarrhythmias and sudden cardiac death (SCD). Certain drugs (propofol, local anaesthetics), fever, bradycardia, increased vagal tone and electrolyte imbalances can trigger or worsen BrS arrhythmias.

OBJECTIVE
To evaluate the incidence of malignant ventricular arrhythmias during the perioperative period in patients with BrS, hypothesising that common anaesthetic drugs may be safe to use during daily clinical practice.

DESIGN
The BRUGANAES study was an observational, retrospective project including BrS patients who underwent various types of anaesthesia.

SETTING
BrS patients undergoing any type of anaesthesia intervention from 1 January 2006, to 31 December 2023, from a tertiary hospital in Barcelona.

MAIN OUTCOME MEASURES
The primary outcome was the occurrence of malignant ventricular arrhythmias and/or SCD during and up to 30 days postanaesthesia. Secondary outcomes included adverse events during hospitalisation, 30-day readmission rates and 30-day mortality rates.

RESULTS
Among 652 BrS patients registered in the hospital, 111 patients and 189 procedures were analysed. General anaesthesia was administered in 51.3% of cases, sedation in 36% and regional/neuraxial anaesthesia exclusively in 12.7%. Overall, nonrecommended drugs (propofol, ketamine and local anaesthetics) were used in 129 (68.3%) procedures, either bolus and/or continuous infusion. Epidural blocks were performed in 34% of regional anaesthesia cases, mostly in obstetrics, and subarachnoid blocks in 31.8%. The primary outcome occurred in two patients intraoperatively (1% of procedures): one with bradycardia-induced ventricular fibrillation after a nonrecommended drug and one with transient ventricular tachycardia after a drug not listed as potentially harmful.

CONCLUSION
To date, this is one of the largest cohorts describing the perioperative approach for BrS patients, including a wide range of anaesthesia procedures and drugs. Most of the patients undergoing anaesthesia for an interventional procedure received an anaesthetic drug classified as not recommended.
Pain experience of children with Christianson syndrome
Authors: Premachandran Shajenth , Ocay Don Daniel , Beaulieu Claudie , Balduzzi Jonathan , Ye Diana-Luk , Davidova Albena , Bokhari Rakan , Ouellet Jean A. , Orlowski John , Gendron Louis , Sharif-Naeini Reza , Ferland Catherine E. 
Published: February 2025

Abstract
Children with Christianson syndrome (CS), an X-linked neurodevelopmental disorder caused by loss-of-function mutations in the alkali cation/proton exchanger SLC9A6/NHE6, display severe cognitive impairments, mutism, and sensory abnormalities such as hyposensitivity to pain. However, it is unclear whether these children display other sensory abnormalities and whether their pain hyposensitivity is the result of an elevated pain threshold or a complete insensitivity to pain. To better characterize the sensory abnormalities in this disorder, we used a combination of a mouse model of CS and pain questionnaires directed at nonverbal patients with CS. We recruited 14 young male participants with CS and subjected them to a novel observational tool, the Pain Sensory and Painful Situations Questionnaire (PSQ), which takes multiple painful situations into account to broaden the description of pain expression. By analyzing social expressive behaviours of pain in these nonverbal patients, the PSQ documented that over 60% of the participants were unaffected by mechanical or inflammatory painful stimuli. This reduced pain sensitivity was also observed in the mouse CS model. Surprisingly, CS mice also displayed aversive reactions to innocuous stimuli, which prompted us to examine whether such reactions were also present in children with CS. Indeed, the results from the PSQ revealed that 30% to 50% of these patients showed an aversive response to normally innocuous stimuli like light touch and gusts of air. Our results demonstrate that children with CS have aversive reactions to innocuous stimuli and are hyposensitive to painful stimuli, the latter making them at risk for developing complications from unreported injuries.