bluuebunny/crossref_metadata_2025 huggingface dataset:
Prognostic value of antepartum alkaline phosphatase, total and ionized calcium and net acid/base excretion to predict peripartum hypocalcemia in cows
Authors: Arnold Benjamin , Khol Johannes Lorenz , Wittek Thomas
Published: February 2025

The aim of this study was to evaluate parameters for the prediction of peripartum hypocalcemia in cattle. The study consisted of two independent investigations (A and B) conducted in different time periods and locations. Blood sera were analyzed for the activity of alkaline phosphatase (ALP), the concentration of ionized (iCa), and total calcium (Ca) two weeks before calving. On the day of calving, urinary net acid/base excretion was calculated, and the serum Ca concentration was analyzed. Ca concentration less than 2 mmol/l on the day of calving was defined as hypocalcemia. The results differed between the two investigations. Part A showed high predictive values for the antepartum parameters ALP and Ca concentration, but these could not be replicated in part B. Animals enrolled were quite young (average age 5.5 years) and the group of animals with hypocalcemia was comparably small in both investigations. The reason(s) for the different results in investigation A and B are not clear. These findings indicate that there are probably as yet unidentified parameters and influences on calcium homeostasis in cattle. None of the parameters investigated in the present study can be considered a reliable universal parameter for prediction of hypocalcemia risk in general.
Experiences of early assessment to teach functional programming
Authors: CHAPMAN PETER
Published: February 2025

This paper reports on the experiences of using an early assessment intervention, specifically employing a Use-Modify-Create scaffold, to teach first-year undergraduate functional programming. The particular intervention that was trialled was the use of an early assessment instrument, in which students had to use code given to them, or slightly modify it, to achieve certain goals. The intended outcome was that the students would thus engage earlier with the functional language, enabling them to be better prepared for the second piece of assessment, where they create code to solve given problems. This intervention showed promise: the difference between a student’s score on the Create assignment improved by an average of 9% in the year after the intervention was implemented, a small effect.
Collective Reflective Equilibrium, Algorithmic Bioethics and Complex Ethics
Authors: Savulescu Julian
Published: February 2025

John Harris has made many seminal contributions to bioethics. Two of these are in the ethics of resource allocation. Firstly, he proposed the “fair innings argument” which was the first sufficientarian approach to distributive justice. Resources should be provided to ensure people have a fair innings—when Harris first wrote this, around 70 years of life, but perhaps now 80. Secondly, Harris famously advanced the egalitarian position in response to utilitarian approaches to allocation (such as maximizing Quality Adjusted Life Years [QALYs]) that what people want is the greatest chance of the longest, best quality life for themselves, and justice requires treating these claims equally. Harris thus proposed both sufficientarian and egalitarian approaches. This chapter compares these approaches with utilitarian and contractualist approaches and provides a methodology for deciding among these (Collective Reflective Equilibrium). This methodology is applied to the allocation of ventilators in the pandemic (as an example) and an ethical algorithm for their deployment created. This paper describes the concept of algorithmic bioethics as a way of addressing pluralism of values and context specificity of moral judgment and policy, and addressing complex ethics.
Transcatheter closure of atrial and ventricular septal defects in patients with dextrocardia: a clinical analysis
Authors: Xiao Jiawang , Zhu Xianyang , Wang Jianming , Wang Zhongchao , Geng Jingsong , Wang Qiguang
Published: February 2025

Objective:

To assess the feasibility of transcatheter closure in patients with dextrocardia and isolated atrial septal defect or ventricular septal defect.

Methods:

A retrospective analysis was performed on the clinical data of 10 patients with dextrocardia and atrial septal defect or ventricular septal defect from June 2013 to January 2023 and successfully underwent transcatheter closure. Patient data were meticulously collected.

Results:

The study cohort comprised 10 patients, with three males, aged between 3 and 38 years. Intraoperative right heart catheterisation revealed the following measurements: the mean pulmonary arterial pressure of 20.5(18,24,3) mmHg, and a pulmonary-to-systemic flow ratio of 1.80(1.58,2.15). There were five atrial septal defects, with defect diameters of 26(20,30) mm, comprising three dextroversion and two mirror-image dextrocardia. Intraoperative echocardiography confirmed the absence of any residual shunt. Among them, a patient with mirror-image dextrocardia, atrial septal defects, and interrupted inferior vena cava required an alternative approach due to femoral vein limitations. The right internal jugular vein was punctured, and a 22 mm atrial septal occluder was successfully deployed via this route. The study identified five ventricular septal defects, with defect diameters of 4(3.5,5.5) mm, including two dextroversion and three mirror-image dextrocardia. Upon post-operative repeat left ventriculography, no residual shunt was detected in all but one case, which exhibited a minimal residual shunt. Throughout the perioperative period and subsequent post-operative follow-up, no severe complications were observed.

Conclusion:

For patients with dextrocardia accompanied by simple CHD, transcatheter closure is a viable option when interventional treatment is indicated. Although transcatheter closure of atrial septal defects or ventricular septal defect in patients with dextrocardia presents unique challenges, it is safe and effective when the anatomical nuances of dextrocardia are thoroughly understood.
Concordance of Australian state and territory government guidelines for classifying the healthiness of foods in public settings
Authors: Backman Bettina , Adam Meg , Chan Jasmine , Marshall Josephine , Rosewarne Emalie , Sacks Gary , Cameron Adrian J. , Blake Miranda R.
Published: February 2025

Objective:

To investigate the concordance between Australian government guidelines for classifying the healthiness of foods across various public settings.

Design:

Commonly available products in Australian food service settings across eight food categories were classified according to each of the seventeen Australian state and territory food classification guidelines applying to public schools, workplaces and healthcare settings. Product nutrition information was retrieved from online sources. The level of concordance between each pair of guidelines was determined by the proportion of products rated at the same level of healthiness.

Setting:

Australia.

Participants:

No human participants.

Results:

Approximately half (56 %) of the 967 food and drink products assessed were classified as the same level of healthiness across all fifteen ‘traffic light’-based systems. Within each setting type (e.g. schools), pairwise concordance in product classifications between guidelines ranged from 74 % to 100 %. ‘Vegetables’ (100 %) and ‘sweet snacks and desserts’ (78 %) had the highest concordance across guidelines, while ‘cold ready-to-eat foods’ (0 %) and ‘savoury snacks’ (23 %) had the lowest concordance. In addition to differences in classification criteria, discrepancies between guidelines arose from different approaches to grouping of products. The largest proportion of discrepancies (58 %) were attributed to whether products were classified as ‘Red’ (least healthy) or ‘Amber’ (moderately healthy).

Conclusions:

The results indicate only moderate concordance between all guidelines. National coordination to create evidence-based consistency between guidelines would help provide clarity for food businesses, which are often national, on how to better support community health through product development and reformulation.
Sneak Peek: Food, Waste, and Packaging Characteristics of South Australian School Children’s Lunchboxes
Authors: Lalchandani Neha Kishan , Hume Clare , Giles Lynne , Crabb Shona , Hendrikx Jo , Miller Caroline
Published: February 2025

Objective:

To characterise children’s lunchbox contents for food, waste, and packaging.

Design:

A cross-sectional study was conducted. Lunchboxes were photographed at two time points on the same day: before first morning break to capture food and packaging and post-lunch break to capture food waste. Contents were coded using an audit tool developed using REDCap.

Setting:

23 sites across metropolitan Adelaide, South Australia including 14 preschools and 9 primary schools in low (n=8), medium (n=7), and high (n=8) socioeconomic areas.

Participants:

Preschool (3-5 years) to Grade 7 (6-13 years) school students.

Results:

673 lunchboxes were analysed. Grain foods dominated (with at least half of them being discretionary varieties), with 92% of lunchboxes having at least one item from that category, followed by fruits (78%), snacks (62%), dairy (32%), and vegetables (26%). Lunchboxes of preschool children contained more fruits (92% vs 65%; χ2(1)=73.3, P<0.01), vegetables (36% vs 16%; χ2(1)=34.0, P<0.01), and dairy items (45% vs 19%; χ2(1)=53.6, P<0.01), compared to lunchboxes of primary school children. Snack foods were more prevalent in primary school (68%) than preschool (55%; χ2(1)=11.2, P<0.01). Discretionary foods appeared more frequently, and single-use packaging accounted for half (53%) of all packaging in lunchboxes, primarily from snacks and grain foods. Preschool children had less single-use packaging but more food waste. Vegetables were the most wasted food group.

Conclusions:

Sandwiches, fruits, and various snacks are typical lunchbox foods, often accompanied by single-use packaging. Considering both health and environmental factors in lunchbox choices could benefit children and sustainability efforts in schools.
Novel educational strategies to improve the telemedicine clinical skills of medical students
Authors: Greengold Judith , Spahic Harisa , Serwint Janet , Dlhosh Sharon , Barouch Lili , Gattamorta Karina , Pahwa Amit , Hughes Helen
Published: February 2025

Aim:

Test educational interventions to increase the quality of care in telemedicine.

Background:

Telemedicine (TM) has become an essential tool to practise medicine around the world. However, education to address clinical skills in TM remains an area of need globally across the health professions. We aim to evaluate the impact of a pilot online learning platform (OLP) and standardized coaching programme on the quality of medical student TM clinical skills.

Methods:

A randomized pilot study was conducted with fourth-year medical students (n = 12). All participants engaged in video-recorded standardized patient (SP) simulated encounters to assess TM clinical skills before and after the intervention. Participants were randomized to either the OLP or OLP + Virtual Coaching Institute (VCI) intervention cohort. Quantitative and qualitative data were collected to address self-reported skills, attitudes, and self-efficacy before the 1st SP encounter and after the 2nd SP encounter. SP encounter recordings were scored by two blinded non-investigator raters based on a standardized rubric to measure the change in TM care delivered pre- and post-intervention. Statistical analysis of quantitative data included descriptive statistics and mixed effects ANOVA.

Findings:

Recruitment and retention of participants exceeded expectations, pointing to significant enthusiasm for this educational opportunity. Self-reported skills and scored simulation skills demonstrated significant improvements for all participants receiving the interventions. Both OLP and VCI interventions were well received, feasible, and demonstrated statistically significant efficacy in improving TM clinical skills. Participants who received coaching described more improvements in self-efficacy, confidence, and overall virtual clinical skills. This study provides evidence that virtualized clinical learning environments can positively impact the development of TM clinical skills among medical students. As TM continues to evolve, the implementation of innovative training approaches will be crucial in preparing the next generation of healthcare professionals for the demands of modern healthcare delivery.
Design of dual-band filtering patch antenna slot coupling feed
Authors: Jiang Tiezhen , Zhuang Long , Wang Jianhua , An Qi
Published: February 2025

A novel microstrip filtering antenna with slot coupling feed is presented in this work. An asymmetric interdigital coupling structure is used for the feed to excite the patch antenna through gap-fed coupling. Introducing a U-shaped slot on the patch surface modifies the current path to attain different resonant modes. The asymmetric coupled fingers in the low-frequency band generate a radiation null of −64 dBi, while additional resonances introduced in the high band broaden the bandwidth from 4.9 to 5.3 GHz. A horizontally shorted microstrip branch produces another null point of −28 dBi between the bands, enabling steeper roll-off and further improvement in frequency selectivity. The proposed filtering antenna provides a flexible filter response without requiring extra filtering circuits, with appreciable peak gains (6.1 dBi and 7.1 dBi) and stable radiation characteristics. This makes it suitable for WLAN (Wireless Local Area Network) and ISM (Industrial Scientific Medical) systems applications.
Semiotics of Naming: Narrating and Meaning-Making of the Place Ieodo
Authors: Lee Yunhee
Published: February 2025

This paper aims to explore human beings as language animals, examining how language shapes them in the lifeworld. Biosemiotics and anthroposemiotics are both geared toward studying the relations between life and the environment. This paper thus concerns the semiotics of naming, exploring naming as meaning-making activity based on the interrelation of language and narrative. There are two ways of looking at the language functions in the act of naming. One is “languaging,” which is geared toward producing intimacy with the surrounding world in nature by naming things to establish a relationship with them. The other is “narrating,” which generates a dialogic relationship with fellow human beings by storytelling based on existence and place. This enables humans to cultivate the selves through semiotic cultural activity. Thus, I shall elaborate the semiotic process in naming and narrating things, which leads to culture-making activity, by analyzing the place Ieodo off the south coast of Korea within the biosemiotic perspective which connects language and cognition with the narrative world for culture-making activity.
Integrated Remote Sensing for Enhanced Drought Assessment: A Multi‐Index Approach in Rajasthan, India
Authors: Agarwal Vivek , Vishvendra Raj Singh Bhanwar , Marsh Stuart , Qin Zhengyuan , Sen Anjan , Kulhari Khusbhu
Published: February 2025

This study investigates land use, land cover (LULC) changes, vegetation health, and drought severity in Rajasthan, India, from 1985 to 2020 using remote sensing techniques. By analyzing satellite imagery with the normalized difference vegetation index (NDVI), temperature condition index (TCI), vegetation condition index (VCI), and NDVI deviation (Dev_NDVI), we assess the spatial and temporal dynamics of the region's landscape and drought conditions. Our findings indicate significant LULC changes, including a decrease in water bodies from 6412.87 to 2248.51 km2 and dense forests by 61.37%, while built‐up areas expanded by 890.50%, reflecting substantial human impact and environmental change. Drought analysis revealed that nearly 49% of the study area experienced moderate to severe drought conditions, with VCI levels below 40%, indicating widespread drought impact across different regions and time periods. The study employs weighted sum analysis of Dev_NDVI, VCI, and TCI to create a detailed drought severity map, revealing areas of severe and extreme drought that necessitate immediate action for sustainable management. The novelty of this approach lies in its integrated multi‐index method for assessing drought over a 35 year period, providing a robust framework for analyzing environmental dynamics and the resilience of ecosystems to climatic stresses. This research emphasizes the value of remote sensing for continuous environmental monitoring and highlights future implications for integrating advanced satellite technologies to enhance drought management strategies, ultimately informing policy decisions for sustainable land and water resource management in Rajasthan and similar semi‐arid regions globally.
Quantifying Geomagnetic Activity's Contribution to the Global E‐Region Electron Density's Day‐To‐Day Variability Using Spire Radio Occultation Observations
Authors: Salinas Cornelius Csar Jude H. , Wu Dong L. , Qian Liying
Published: February 2025

Using the unprecedented sampling of the Spire Radio Occultation (RO) data set, this paper statistically estimates geomagnetic dependencies of the global E‐region Electron Density's (Ne) day‐to‐day variability. To assesses how much Spire RO‐observed variabilities are consistent with known Physics, comparison is made with the Specified Dynamics–Whole Atmosphere Community Climate Model with Ionosphere/Thermosphere eXtension (SD‐WACCM‐X), a first principles Physics‐based model. Results show that the largest geomagnetic dependency on Spire and SD‐WACCM‐X E‐region Ne occurs at night over the auroral latitudes with coefficients of determination at around 49% and 80%, respectively. Their regression coefficients are both between +10%/Kp index to +16%/Kp index. On the other hand, Spire and SD‐WACCM‐X substantially disagree on the geomagnetic dependencies during day‐time. These results suggest that Spire RO's observations of E‐region Ne geomagnetic dependencies may only be substantially explained by known physics at night and not during the day.
Diurnal and Seasonal Variations of Gravity Waves in the Lower Atmosphere of Mars as Observed by InSight
Authors: Hernández‐Bernal J. , Spiga A. , Chatain A. , Pla‐Garcia J. , Banfield D.
Published: February 2025

We investigate Gravity Waves (GWs) in the lower atmosphere of Mars based on pressure timeseries acquired by the InSight lander. We compile a climatology showing that most GW activity detected at the InSight landing site takes place after the sunrise and sunset; they are almost absent during the aphelion season, and more prominent around the equinoxes, with variations during dust events and interannual variations. We find GWs with coherent phases in different sols, and a previously unnoticed coincidence of GW activity with those moments in which the diurnal cycle (of tidal origin) exhibits the fastest increases in absolute pressure. We explore the possibility that some of these GWs might actually be high‐order harmonics of thermal tides transiently interfering constructively to produce relevant meteorological patterns, and discuss other interpretations based on wind patterns. The so‐called Terminator Waves observed on Earth might also explain some of our observations.
Phospholipase C β4 promotes RANKL-dependent osteoclastogenesis by interacting with MKK3 and p38 MAPK
Authors: Lee Dong-Kyo , Jin Xian , Choi Poo-Reum , Cui Ying , Che Xiangguo , Lee Sihoon , Hur Keun , Kim Hyun-Ju , Choi Je-Yong
Published: February 2025

Phospholipase C β (PLCβ) is involved in diverse biological processes, including inflammatory responses and neurogenesis; however, its role in bone cell function is largely unknown. Among the PLCβ isoforms (β1–β4), we found that PLCβ4 was the most highly upregulated during osteoclastogenesis. Here we used global knockout and osteoclast lineage-specific PLCβ4 conditional knockout (LysM-PLCβ4

−/−
) mice as subjects and demonstrated that PLCβ4 is a crucial regulator of receptor activator of nuclear factor κB ligand (RANKL)-induced osteoclast differentiation. The deletion of PLCβ4, both globally and in the osteoclast lineage, resulted in a significant reduction in osteoclast formation and the downregulation of osteoclast marker genes. Notably, male LysM-PLCβ4

−/−
mice presented greater bone mass and fewer osteoclasts in vivo than their wild-type littermates, without altered osteoblast function. Mechanistically, we found that PLCβ4 forms a complex with p38 mitogen-activated protein kinase (MAPK) and MAPK kinase 3 (MKK3) in response to RANKL-induced osteoclast differentiation, thereby modulating p38 activation. An immunofluorescence assay further confirmed the colocalization of PLCβ4 with p38 after RANKL exposure. Moreover, p38 activation rescued impaired osteoclast formation and restored the reduction in p38 phosphorylation caused by PLCβ4 deficiency. Thus, our findings reveal that PLCβ4 controls osteoclastogenesis via the RANKL-dependent MKK3–p38 MAPK pathway and that PLCβ4 may be a potential therapeutic candidate for bone diseases such as osteoporosis.
Macrophages: a double-edged sword in female reproduction and disorders
Authors: Park Mira , Kim Yeon Sun , Song Haengseok
Published: February 2025

Reproduction consists of sequential inflammation-like events, primarily within the endometrium, from ovulation to embryo implantation, decidualization and delivery. During the reproductive cycle, the endometrium repeatedly undergoes cyclic periods of proliferation, differentiation, tissue breakdown and repair without scarring. Owing to their phagocytic activity, macrophages, key players in innate immunity, are thought to play crucial roles in the endometrium. Endometrial macrophages actively participate in various stages of reproductive tissue remodeling, particularly during decidualization and pregnancy establishment. Traditionally considered simple bystanders that clear debris to prevent autoimmune responses in tissue homeostasis, macrophages are now recognized as main actors with broad functional plasticity that allows them to fine tune the balance between pro- and anti-inflammatory responses during tissue inflammation, remodeling and repair. Homeostatic balance is determined by the sum of various mediators produced by two distinctly polarized macrophage subpopulations. The biased polarization of tissue-resident macrophages may contribute to the pathogenesis of various diseases, such as inflammation and cancer. Thus, understanding how macrophages contribute to endometrial homeostasis is crucial for deciphering the underlying mechanisms of various reproductive disorders. Nanomedicines using extracellular vesicles, nanoparticles and noncoding RNAs have recently been applied to modulate macrophage polarization and alleviate disease phenotypes. Despite these advances, the functions of endometrial macrophages under physiological and pathophysiological conditions remain poorly understood, which complicates the development of targeted therapies. Here we update the current understanding of the homeostatic function of macrophages and the putative contribution of endometrial macrophage dysfunction to reproductive disorders in women, along with innovative molecular therapeutics to resolve this issue.
Serotonin attenuates tumor necrosis factor-induced intestinal inflammation by interacting with human mucosal tissue
Authors: Bosáková Veronika , Papatheodorou Ioanna , Kafka Filip , Tomášiková Zuzana , Kolovos Petros , Hortová Kohoutková Marcela , Frič Jan
Published: February 2025

The intestine hosts the largest immune system and peripheral nervous system in the human body. The gut‒brain axis orchestrates communication between the central and enteric nervous systems, playing a pivotal role in regulating overall body function and intestinal homeostasis. Here, using a human three-dimensional in vitro culture model, we investigated the effects of serotonin, a neuromodulator produced in the gut, on immune cell and intestinal tissue interactions. Serotonin attenuated the tumor necrosis factor-induced proinflammatory response, mostly by affecting the expression of chemokines. Serotonin affected the phenotype and distribution of tissue-migrating monocytes, without direct contact with the cells, by remodeling the intestinal tissue. Collectively, our results show that serotonin plays a crucial role in communication among gut–brain axis components and regulates monocyte migration and plasticity, thereby contributing to gut homeostasis and the progression of inflammation. In vivo studies focused on the role of neuromodulators in gut inflammation have shown controversial results, highlighting the importance of human experimental models. Moreover, our results emphasize the importance of human health research in human cell-based models and suggest that the serotonin signaling pathway is a new therapeutic target for inflammatory bowel disease.
Increased oxidative phosphorylation through pyruvate dehydrogenase kinase 2 deficiency ameliorates cartilage degradation in mice with surgically induced osteoarthritis
Authors: Han Jin , Kim Yoon Hee , Han Seungwoo
Published: February 2025

Chondrocytes can shift their metabolism to oxidative phosphorylation (OxPhos) in the early stages of osteoarthritis (OA), but as the disease progresses, this metabolic adaptation becomes limited and eventually fails, leading to mitochondrial dysfunction and oxidative stress. Here we investigated whether enhancing OxPhos through the inhibition of pyruvate dehydrogenase kinase (PDK) 2 affects the metabolic flexibility of chondrocytes and cartilage degeneration in a surgical model of OA. Among the PDK isoforms, PDK2 expression was increased by IL-1β in vitro and in the articular cartilage of the DMM model in vivo, accompanied by an increase in phosphorylated PDH. Mice lacking PDK2 showed significant resistance to cartilage damage and reduced pain behaviors in the DMM model. PDK2 deficiency partially restored OxPhos in IL-1β-treated chondrocytes, leading to increases in APT and the NAD+/NADH ratio. These metabolic changes were accompanied by a decrease in reactive oxygen species and senescence in chondrocytes, as well as an increase in the expression of antioxidant proteins such as NRF2 and HO-1 after IL-1β treatment. At the signaling level, PDK2 deficiency reduced p38 signaling and maintained AMPK activation without affecting the JNK, mTOR, AKT and NF-κB pathways. p38 MAPK signaling was critically involved in reactive oxygen species production under glycolysis-dominant conditions in chondrocytes. Our study provides a proof of concept for PDK2-mediated metabolic reprogramming toward OxPhos as a new therapeutic strategy for OA.
Rheumatoid arthritis severity is mediated by crosstalk between synoviocytes and mature osteoclasts through a calcium and cytokine feedback loop
Authors: Lee Eun Sun , Kim Hyeong Jae , Lee Dongun , Kang Jung Yun , Shin Dong Min , Hong Jeong Hee
Published: February 2025

Fibroblast-like synoviocytes (FLSs) and osteoclasts are central cells in the maintenance of joint homeostasis. Rheumatoid arthritis (RA) is a chronic inflammatory disease of joints that induces cytokine-activated FLSs and progressive bone erosion. Interactions between FLSs and other cells, such as T cells and B cells, have been recognized in the development of RA. Here we hypothesized that calcium released from bone by mature osteoclasts might activate FLSs, which are also affected by inflammatory cytokines in the inflamed synovium. Osteoclastogenesis occurs in the presence of cytokine-stimulated FLS medium, and calcium released from the bone disc activates FLS migration. We first investigated the calcium and cytokine feedback loop between FLSs and osteoclast maturation. Moreover, by addressing the role of the sodium-bicarbonate cotransporter NBCn1 in osteoclastogenesis, we found that the inhibition of NBCn1 attenuated the infinite calcium and cytokine feedback loop between FLSs and osteoclasts. In a collagen-induced arthritis mouse model, the inhibition of NBC reduced the RA pathological phenotype and bone resorption area in the femur. These results suggest that modulation of the crosstalk between FLSs and osteoclasts by inhibiting the calcium and cytokine feedback loop could be considered to develop pioneering strategies to combat RA severity and dysregulated bone homeostasis.
Neddylation of RhoA impairs its protein degradation and promotes renal interstitial fibrosis progression in diabetic nephropathy
Authors: Li Xue-qi , Jin Bo , Liu Si-xiu , Zhu Yan , Li Nan , Zhang Qing-yan , Wan Cheng , Feng Yuan , Xing Yue-xian , Ma Kun-ling , Liu Jing , Jiang Chun-ming , Lu Jian
Published: February 2025

Diabetic nephropathy (DN) is a common and serious complication of diabetes, characterized by chronic fibro-inflammatory processes with an unclear pathogenesis. Renal fibrosis plays a significant role in the development and progression of DN. While recent research suggests that the neddylation pathway may influence fibrotic processes, its specific dysregulation in DN and the underlying mechanisms remain largely unexplored. This study identified the neddylation of RhoA as a novel post-translational modification that regulates its expression and promotes renal fibrosis in DN. We here demonstrated that two key components of the neddylation pathway—NEDD8-activating enzyme E1 subunit 1 (NAE1) and NEDD8—are significantly upregulated in human chronic kidney disease (CKD) specimens compared to healthy kidneys, implicating neddylation in CKD-associated fibrosis. Our findings further revealed that both pharmacological inhibition of neddylation using MLN4924 and genetic knockdown of NAE1 mitigate renal fibrosis in mouse models of streptozotocin-induced diabetes and unilateral ureteral obstruction (UUO). Immunoprecipitation-mass spectrometry (IP-MS) and subsequent function assays demonstrated a direct interaction between RhoA and NEDD8. Importantly, neddylation inhibition reduced RhoA protein expression, highlighting a potential therapeutic target. Additionally, a positive correlation was noted between elevated NEDD8 mRNA levels and RhoA mRNA expression in human CKD specimens. RhoA overexpression counteracted the antifibrotic effects of neddylation inhibition, underscoring its critical role in fibrosis progression. Mechanistically, we unveiled that neddylation enhances RhoA protein stability by inhibiting its ubiquitination-mediated degradation, which subsequently activates the ERK1/2 pathway. Collectively, this study provides novel insights into NAE1-dependent RhoA neddylation as a key contributor to renal fibrosis in DN.
Effects of mixing of europium oxide in resin composites on the fluorescence characteristics and mechanical properties
Authors: Utsumi Yuta , Oishi Masatsugu , Yonekura Kazuhide , Ikeda Masaomi , Matsuki Yusuke , Ohge Kenichiro , Iuchi Tomoki , Hosaka Keiichi
Published: February 2025

Objective

The objective of this study is to disperse europium oxide (Eu2O3) in a resin composite (RC) using a planetary centrifugal mixer and assess its effects on photoluminescence and mechanical properties.

Materials and methods

A commercially available RC was mixed with Eu2O3 at various concentrations using a planetary centrifugal mixer. The fabricated samples were evaluated using scanning electron microscopy and a spectrofluorometer to assess their crystal structures, particle sizes, and photoluminescence properties. Vickers microhardness measurements were performed, along with a three-point bending test. Statistical analyses were performed to assess the mechanical properties.

Results

The intensity of red fluorescence increased with the increase of europium oxide concentration. The fluorescence spectra at 613 and 620 nm exhibited higher intensities under excitation at 254 nm. Eu2O3 was dispersed in RC regardless of the Eu2O3 concentration, and no aggregation was observed. Regarding the mechanical properties, there were no significant differences in the flexural strength or modulus, and the Vickers hardness gradually increased with increasing Eu2O3 concentration.

Conclusion

To mix Eu2O3 with RC, visible fluorescence emission was observed even with increasing the Eu2O3 concentration, and the mechanical properties of RC were unaffected. Based on our study, a 15 wt% concentration of Eu₂O₃ is the appropriate concentration, as it achieves strong fluorescence emission without compromising the mechanical properties or color tone of the RC.
Mechanisms and therapeutic potential of the hedgehog signaling pathway in cancer
Authors: Cong Ge , Zhu Xingyu , Chen Xin Ru , Chen Hao , Chong Wei
Published: February 2025

A sort of major malignant disease, cancer can compromise human health wherever. Some mechanisms of the occurrence and evolution of cancer still seem elusive even now. Consequently, the therapeutic strategies for cancer must continually evolve. The hedgehog signaling pathway, a critical mediator in the normal development of numerous organs and the pathogenesis of cancer, is typically quiescent but is aberrantly activated in several malignancies. Extensive research has delineated that the aberrant activity of the hedgehog signaling pathway, whether autocrine or paracrine, is implicated in the initiation and progression of various neoplasms, including medulloblastoma (MB), basal cell carcinoma (BCC) and so on. Thus, notably Smo inhibitors, the opening of inhibitors of the hedgehog signaling pathway has become a topic of research attention. This review aims to summarize four aberrant activation pathways and the influence of hedgehog signaling pathway associated chemicals on tumor formation and development. Additionally, it will explore the therapeutic potential of targeted interventions in the hedgehog signaling pathway for cancer treatment.
The role of the social worker in the assessment and management of adults receiving Home Parenteral Nutrition
Authors: Carey Sharon , Brown Shannyn , Ferrie Suzie
Published: February 2025

People diagnosed with Intestinal Failure (IF) requiring Home Parenteral Nutrition (HPN) have complex medical and nutritional requirements. To date, assessment for, and ongoing management of, HPN has relied on medical, nursing and dietetic input. However, success in assessing suitability for HPN and ongoing management is often reliant on non-medical factors. This paper aims to outline the critical clinical role the social worker can play and their scope of practice in assessing and managing people requiring HPN. This includes assessment across medical, psychosocial, financial, legal, quality-of-life and healthcare-related domains. This perspective paper highlights the vast scope in which the social worker can support people diagnosed with IF requiring HPN. More research is required to quantify the value of the social worker as a key member of the multidisciplinary IF team.
Optical widefield nuclear magnetic resonance microscopy
Authors: Briegel Karl D. , von Grafenstein Nick R. , Draeger Julia C. , Blümler Peter , Allert Robin D. , Bucher Dominik B.
Published: February 2025

Microscopy enables detailed visualization and understanding of minute structures or processes. While cameras have significantly advanced optical, infrared, and electron microscopy, imaging nuclear magnetic resonance (NMR) signals on a camera has remained elusive. Here, we employ nitrogen-vacancy centers in diamond as a quantum sensor, which converts NMR signals into optical signals that are subsequently captured by a high-speed camera. Unlike traditional magnetic resonance imaging, our method records the NMR signal over a wide field of view in real space. We demonstrate that our optical widefield NMR microscopy can image NMR signals in microfluidic structures with a ~10 μm resolution across a ~235 × 150 μm2 area. Crucially, each camera pixel records an NMR spectrum providing multicomponent information about the signal’s amplitude, phase, local magnetic field strengths, and gradients. The fusion of optical microscopy and NMR techniques enables multifaceted imaging applications in the physical and life sciences.
Anti-Ebola virus mAb 3A6 protects highly viremic animals from fatal outcome via binding GP(1,2) in a position elevated from the virion membrane
Authors: Hastie Kathryn M. , Salie Zhe Li , Ke Zunlong , Halfmann Peter J. , DeWald Lisa Evans , McArdle Sara , Grinyó Ariadna , Davidson Edgar , Schendel Sharon L. , Hariharan Chitra , Norris Michael J. , Yu Xiaoying , Chennareddy Chakravarthy , Xiong Xiaoli , Heinrich Megan , Holbrook Michael R. , Doranz Benjamin , Crozier Ian , Kawaoka Yoshihiro , Branco Luis M. , Kuhn Jens H. , Briggs John A. G. , Worwa Gabriella , Davis Carl W. , Ahmed Rafi , Saphire Erica Ollmann
Published: February 2025

Monoclonal antibodies (mAbs) against Ebola virus (EBOV) glycoprotein (GP1,2) are the standard of care for Ebola virus disease (EVD). Anti-GP1,2 mAbs targeting the stalk and membrane proximal external region (MPER) potently neutralize EBOV in vitro and are protective in a mouse model of EVD. However, their neutralization mechanism is poorly understood because they target a GP1,2 epitope that has evaded structural characterization. Using X-ray crystallography and cryo-electron tomography of mAb 3A6 complexed with its stalk–MPER epitope, we reveal a previously undescribed mechanism in which 3A6 binds to a conformation of GP1,2 that is lifted from the virion membrane. We further show that in both domestic guinea pig and rhesus monkey EVD models, 3A6 provides therapeutic benefit at high-viremia advanced disease stages and at the lowest dose yet demonstrated for any anti-EBOV mAb-based monotherapy. The findings reported here can guide design of next-generation highly potent anti-EBOV therapeutics and vaccines.
RF communication between dual band implantable and on body antennas for biotelemetry application
Authors: Kamel Yara A. , Mohamed Hesham A. , ELsadek Hala , ELhennawy Hadia M.
Published: February 2025

This paper investigates two antennas for implantable communication, which are a wide-band, low-profile transmitting antenna with a circular polarization (CP) merit immersed in a lossy medium and a corresponding wide-band, low-profile receiving antenna with a linear polarization (LP) merit placed on human tissue. The first antenna is implantable inside a human body for sensing, monitoring, and transmitting various vital signs, while the second antenna acts as a nearby receiving end. These antennas work in the 2.4-2.4835 GHz and 5.725-5.875 GHz industrial, scientific, and medical (ISM) bands. The main features of the designed transmitting antenna are its simplicity, the wide-band characteristics, which preserve the detuning effect caused by environmental heterogeneity, and the CP property at both operational ISM bands. Moreover, for introducing an electrically small antenna footprint with proper performance, the implantable antenna is designed with an entire size of 25.4 (5
$$\times$$
5
$$\times$$
1.016)
$$\hbox {mm}^3$$
. This antenna is designed and dissected in a homogeneous skin model (HSM) as well as a three-layer phantom. On the other hand, the wide-band receiving antenna is designed on flexible material for patients’ comfort with a compact size of 134.6 (
$$20\times 26.5\times 0.254$$
)
$$\hbox {mm}^3$$
. In addition, the implantable antenna performance is evaluated in a chicken slab as well as a saline solution, while the on-body antenna is placed on the chicken slab to measure its reflection coefficient. The measured impedance BWs of the implantable antenna are 13.04 % and 33.2 % in the chicken slab while 19.5% and 25.2 % in the saline solution at the two ISM bands, respectively. While, the measured impedance BWs of the on-body antenna are 24% and 50.4 % at two operating ISM frequencies. Finally, the measured transmission coefficient between the two antennas is evaluated.
Evaluating experimentally the viability of employing hybrid nanofluids as an operating fluid in a shell-and-tube heat exchanger
Authors: Hassaan Amr M.
Published: February 2025

The use of hybrid nanofluids (HNF) in heat transfer applications has become the subject of studies during recent periods. Its ability to transfer heat is superior to single nanofluids, and this has been proven in many research. Shell and tube heat exchanger is one of the most common types and are therefore always under research to improve their performance. This study is a practical study that examines the effectiveness of HNF in their use as operating fluids in shell-and-tube heat exchangers instead of traditional operating fluids. A laboratory heat exchanger was used to complete this study. A group of HNF (MWCNTs- Al2O3/water) was synthesized at different concentration rates ranging from 0.4 to 2%. Tests were conducted for Reynolds values in the range from 2500 to 12,560. By measuring the variables in the tests and calculating some factors the results showed that, in comparison between the use of HNF and distilled water, it was found that there is an increase in the value of the Nusselt number for the HNF over the distilled water in a range of 10- 28.5%. The effectiveness increased when using the HNF by up to 22.7% compared to distilled water. Through experiments, an equation was deduced to calculate the value of the Nusselt number. There is good agreement between the results of this research and previous literature.
Dielectric function and thermo-optic coefficients of silicon-doped GaN substrates at elevated temperature from 298 K to 873 K in the UV-Vis-NIR spectrum
Authors: Bian Subiao , Chen Xi , Cui Changcai
Published: February 2025

Understanding the thermal influence on gallium nitride (GaN) single crystal substrates is critical for the advancement of GaN-based optoelectronic devices. In this study, we comprehensively characterized the thermal effects on the optical properties of silicon-doped GaN substrates using spectroscopic ellipsometry over a broad wavelength range from 250 nm to 1600 nm. The dielectric function of GaN was determined at temperatures ranging from 298 K to 873 K, demonstrating consistent temperature-dependent behavior. The exciton transitions were precisely characterized and modeled using the empirical Varshni expression. Moreover, we report, for the first time, the thermo-optic coefficients across the wide spectrum, parameterized using a Sellmeier model. This work significantly expand the GaN optical properties database beyond thin films and provide essential insights for the design and optimization of next-generation GaN-based optoelectronic devices.
Exploring biomarkers and molecular mechanisms of Type 2 diabetes mellitus promotes colorectal cancer progression based on transcriptomics
Authors: Luo Simin , Zhu Yuhong , Guo Zhanli , Zheng Chuan , Fu Xi , You Fengming , Li Xueke
Published: February 2025

Type 2 diabetes mellitus (T2DM) has been confirmed as an independent risk factor for colorectal cancer (CRC) in many studies. However, the mechanisms behind T2DM’s role in the progression of CRC remain unclear. This study aims to explore the potential biomarkers and molecular mechanisms involved in T2DM-promoted CRC progression. The limma package was used to identify differentially expressed genes in tumor tissue from CRC patients with or without T2DM. The key biological processes were screened by gene ontology and gene set enrichment analysis. A diagnostic model for co-morbidities was constructed by logistic regression model with least absolute shrinkage and selection operator (Lasso) regularization method. The diagnostic performance was assessed by supplementing external datasets to draw ROC curves on the diagnostic model. The diagnostic model was further screened for key genes by prognostic analysis. The relationship of key genes with immune cells and other cells was evaluated by immune infiltration algorithm and single-cell transcription analysis. Drug prediction was performed by cMAP and the obtained drugs were molecularly docked with the key genes. The differentially expressed genes of T2DM-promoted CRC progression were mainly enriched to O-linked glycosylation-related processes. The diagnostic model constructed based on Lasso logistic regression had good diagnostic performance (AUC > 0.8). COX11 was the key gene for co-morbidities: in tumor tissues, COX11 expression was significantly higher than that in normal colon tissues. However, COX11 gene expression was significantly lower in patients with comorbidities than in patients without T2DM in tumor tissue. External datasets confirmed from both mRNA and protein expression levels that low COX11 expression was significantly associated with poor CRC prognosis. Immune infiltration analysis suggested that its expression related to the proportion of M2 macrophages. Single-cell transcriptome analysis revealed a close association of COX11 expression with endothelial cells and macrophages. The top4 drugs predicted bound well to COX11. Our study revealed that the pathogenesis of T2DM-promoted CRC progression related to O-linked glycosylation. We constructed a diagnostic model for T2DM-CRC co-morbidity. Meanwhile, we identified COX11 as a potential immune-related molecular marker closely associated with T2DM-promoted CRC progression. These mechanisms and molecular markers may provide new ideas for further studies of T2DM-promoted CRC progression and contribute to drug discovery for the treatment of co-morbidities.
Type-2 innate signals are dispensable for skeletal muscle regeneration and pathology linked to Duchenne muscular dystrophy
Authors: Messing Melina , Theret Marine , Hughes Michael R , Wu Jiaqi , Syed Omar Husain , Li Fang Fang , Li Yicong , Rossi Fabio M V , McNagny Kelly M
Published: February 2025

Immune responses play an integral role in skeletal muscle regeneration. In the genetically inherited muscle disease Duchenne muscular dystrophy (DMD), muscle regeneration is disrupted, leading to chronic inflammation, fibrosis, and early mortality. Previously, it has been suggested that type-2 innate immune cells, particularly eosinophils and their production of IL-4, play an essential role in effective muscle regeneration after acute injury. We here re-investigate the role of eosinophils in skeletal muscle repair using mice deficient in eosinophils (ΔdblGATA), or deficient in IL-4R/IL-13R signaling through STAT6 (Stat6−/−). We show that neither deficiency has an impact on skeletal muscle regeneration in response to acute injury as quantified by fiber size, immune cell infiltration, or muscle-resident stem cell proliferation. We also investigate the role of STAT6 signaling in mdx:Stat6−/− mice, a model of DMD and, again, find that ablation of STAT6 signaling has no effect on the rate or severity of fibrotic scar formation or disease progression. In contrast to previous models, our data suggest a negligible role for eosinophils and STAT6 signaling in skeletal muscle regeneration after acute or chronic injury.
Non-linear dynamics in ECG: a novel approach for robust classification of cardiovascular disorders
Authors: Kumar Behera Suraj , Bhattacharya Debanjali , Aithal Ninad , Sinha Neelam
Published: February 2025

Detecting cardiac disorders from multi-channel ECG has significant implications for cardiac care. Current methods face challenges due to ECG waveform variations by electrode placement, high signal non-linearity, and low millivolt amplitudes. The present study introduces a non-linear analysis approach leveraging Recurrence plot visualizations as the patterned occurrence of well-defined structures, such as the QRS complex, can be exploited effectively using Recurrence plots. Using the Physikalisch-Technische Bundesanstalt dataset from PhysioNet, we examined four cardiac disorder classes- Myocardial infarction, Bundle branch blocks, Cardiomyopathy, Dysrhythmia, and healthy controls, achieving an impressive classification accuracy of 100%. Wilcoxon rank-sum test is performed at 95% C.I. on Recurrence Quantitative Analysis (RQA) features, identifying five features with statistically significant differences across pairs of study groups. Additionally, t-SNE visualizations of latent space embeddings derived from Recurrence plots and RQA features reveal clear separation among cardiac disorders and healthy subjects, underscoring the efficacy of the proposed approach.