bluuebunny/crossref_metadata_2025 huggingface dataset:
A case of high tibial osteotomy in a patient with psoriatic arthritis
Authors: Koga Mikiro , Maeyama Akira , Ishimatsu Tetsuro , Hagio Tomonobu , Shibata Terufumi , Yamasaki Yutaro , Sugino Yuki , Yamamoto Takuaki
Published: January 2025

Traditionally, patients with rheumatic diseases, such as rheumatoid arthritis (RA), were considered unsuitable for joint-sparing surgery. In the present study, we report on bilateral knee joints affected by psoriatic arthritis coexisting with osteoarthritis, with good, albeit short-term, results. A 62-year-old woman was treated for psoriatic arthritis with a biologic (adalimumab). The Disease Activity in Psoriatic Arthritis index was 7.24, indicating low disease activity. She had been suffering from bilateral knee pain for some time and was treated conservatively by her local doctor, but the pain persisted, and she came to visit us. At the initial visit, tenderness in the medial joint line of both knees and hydrarthrosis in the right knee were observed. Preoprative radiographs at the time of the initial examination showed medial-type osteoarthritis in both knees. First, interlocking closed wedge high tibial osteotomy (CWHTO) was performed on the right knee. This was followed 1 year later by right knee implant removal and interlocking CWHTO on the left knee, with implant removal on the left knee 1 year after that. In both knees preoperatively and postoperatively, the joint range of motion and the Knee Injury and Osteoarthritis Outcome Score total improved Considering the patient’s background, we considered high tibial osteotomy if the disease activity was controlled. However, if the disease worsens in the future, joint destruction may occur, so careful follow-up is necessary.
Metabolic profiling of meningioma reveals novel subgroup-specific biologic insights and outcome dependencies
Authors: Landry Alexander P , Wang Justin Z , Yefet Leeor S , Liu Jeff , Patil Vikas , Zhang Wen-Jiang , Sosa Julio , Ellenbogen Yosef , Gui Chloe , Ajisebutu Andrew , Aldape Kenneth , Gao Andrew , Kislinger Thomas , Chen Eric X , Nassiri Farshad , Zadeh Gelareh
Published: January 2025

Background

Our group and others have recently identified four molecular groups of meningioma, with unique underlying biology and outcomes. The relevance of group-specific metabolite profiles (particularly among hypermetabolic tumors), has not been explored.

Methods

We performed untargeted metabolic profiling of meningiomas representing each molecular group and World Health Organization (WHO) grade. Prognostic biochemicals were identified using Cox regression and their biological importance was explored using RNA and protein-based pathway analyses. Validation was performed using targeted high performance liquid chromatography-mass spectrometry (HPLC-MS/MS).

Results

Global metabolic profiling identified 560 unique biochemicals. We identified a 21-metabolite outcome signature which is strongly predictive of outcome after adjusting for WHO grade, extent of resection, and receipt of adjuvant radiotherapy (HR = 326.49, 95% CI = 16.72-6375.48, P < .0001). The abundance of N6-trimethyllysine was associated with earlier time to recurrence on our whole cohort (log-rank P = .009) and within hypermetabolic and WHO grade 2 tumors specifically; this was validated using targeted HPLC-MS/MS on two cohorts. Consensus RNA and protein expression analysis demonstrated as association between N6-trimethyllysine abundance and activation of oxidative phosphorylation pathways, which portended worse outcomes in the hypermetabolic subgroup but, interestingly, better outcomes in the proliferative subgroup. By contrast, upregulated pyruvate and lactate transporters were associated with worse outcomes in proliferative meningiomas specifically.

Conclusions

This is the first study to demonstrate a subgroup-specific prognostic role of N6-trimethyllysine in hypermetabolic meningiomas, offering increasingly granular outcome predictions using a widely accessible technique (HPLC-MS/MS). We also suggest fundamental differences in preferred energy utilization between and a potential need for subgroup-specific therapies.
Inter-organelle communication dynamically orchestrates juvenile hormone biosynthesis and female reproduction
Authors: Zhu Shiming , Liu Fangfang , Chen Xiaoyi , Xia Sishi , Wu Yingting , Tang Wei , Ren Chonghua , Wang Jian , Li Sheng
Published: January 2025

Inter-organelle communication coordinates cellular homeostasis and function. Juvenile hormone (JH) is produced in the corpora allata (CA) and acts as a gonadotrophic hormone in most insects. Using transcriptomic, biochemical, molecular, and genetic analyses, here we investigated the underlying mechanism how inter-organelle communication dynamically orchestrates JH biosynthesis and female reproduction in the American cockroach, Periplaneta americana. The extracellular stimuli insulin and allatostatin act through their membrane receptors and antagonistically regulate RyR-mediated Ca2+ release from the endoplasmic reticulum in CA cells. Ca2+-activated CaMKII stimulates energy metabolism in the mitochondria partially via SLC25A6, and induces the expression of JH biosynthetic genes HMGR, Jhamt, and Cyp15a1 through activating transcription factor CREB, which recruits CBP for histone acetylation in the nucleus. Additionally, mitochondria interact with CREB-CBP through mitonuclear communication to regulate JH biosynthesis. From the perspective of inter-organelle communication, this comprehensive study significantly advanced our understanding of hormone biosynthesis and reproductive biology in insects.
The translation initiation factor eIF3M2 upregulates HEAT SHOCK PROTEIN 70 to maintain pollen tube membrane integrity during heat shock
Authors: Kahrizi Zahra , Michailidis Christos , Raabe Karel , Kumar Vinod , Honys David , Hafidh Said
Published: January 2025

Pollen germination and pollen tube (PT) growth are extremely sensitive to high temperatures. During heat stress (HS), global translation shuts down and favors the maintenance of the essential cellular proteome for cell viability and protection against protein misfolding. Here, we demonstrate that under normal conditions, the Arabidopsis (Arabidopsis thaliana) eukaryotic translation initiation factor subunit eif3m1/eif3m2 double mutant exhibits poor pollen germination, loss of PT integrity and an increased rate of aborted seeds. Surprisingly, under HS at 37 °C, eif3m1 pollen germination outperformed wild-type Col-0, showing enhanced PT integrity. We established that the improved thermotolerance of the eif3m1 PT was due to increased expression of its putative paralog eIF3M2, which in turn upregulated Heat Shock protein 70 (HSP70) mRNA and protein levels. Indeed, eIF3M2 overexpression upregulated HSP70 expression, whereas eif3m2 knockdown showed reduced HSP70.1 promoter activity and increased in PT burst under HS conditions. Moreover, we show that eIF3M2 coimmunoprecipitates with HSP70 in PTs and directly interacts with cytoplasmic HSP70.1/2/4 and eIF4G in Nicotiana benthamiana pavement cells. Collectively, our data revealed that plants employ the eIF3M2-HSP70 module as a regulator of thermotolerance to maintain PT membrane integrity and improve fertilization and seed set adaptation under high temperatures.
Phosphorylation-dependent VaMYB4a regulates cold stress in grapevine by inhibiting VaPIF3 and activating VaCBF4
Authors: Yu Qinhan , Zheng Qiaoling , Liu Chang , Zhang Junxia , Xie Yaping , Yao Wenkong , Li Jiaxin , Zhang Ningbo , Hao Xinyi , Xu Weirong
Published: January 2025

Cold stress severely impacts the quality and yield of grapevine (Vitis L.). In this study, we extend our previous work to elucidate the role and regulatory mechanisms of Vitis amurensis MYB transcription factor 4a (VaMYB4a) in grapevine's response to cold stress. Our results identified VaMYB4a as a key positive regulator of cold stress. We demonstrated that VaMYB4a undergoes phosphorylation by V. amurensis calcineurin B-like (CBL) proteins-interacting protein kinase 18 (VaCIPK18) under cold stress, a process that activates VaMYB4a transcriptional activity. Using chromatin immunoprecipitation sequencing (ChIP-seq). We performed a comprehensive genomic search to identify downstream components that interact with VaMYB4a, leading to the discovery of a basic helix-loop-helix transcription factor, V. amurensis phytochrome-interacting factor 3 (VaPIF3). VaMYB4a attenuated the transcriptional activity of VaPIF3 through a phosphorylation-dependent interaction under cold conditions. Furthermore, VaPIF3, which interacts with and inhibits V. amurensis C-repeat binding factor 4 (VaCBF4, a known positive regulator of cold stress), has its activity attenuated by VaMYB4a, which mediates the modulation of this pathway. Notably, VaMYB4a also interacted with and promoted the expression of VaCBF4 in a phosphorylation-dependent manner. Our study shows that VaMYB4a positively modulates cold tolerance in plants by simultaneously downregulating VaPIF3 and upregulating VaCBF4. These findings provide a nuanced understanding of the transcriptional response in grapevine under cold stress and contribute to the broader field of plant stress physiology.
A C4 plant K+ channel accelerates stomata to enhance C3 photosynthesis and water use efficiency
Authors: Alvim Fernanda A L S , Alvim Jonas Chaves , Hibberd Julian M , Harvey Andrew R , Blatt Michael R
Published: January 2025

Accelerating stomatal kinetics through synthetic optogenetics and mutations that enhance guard cell K+ flux has proven a viable strategy to improve water use efficiency and biomass production. Stomata of the model C4 species Gynandropsis gynandra, a relative of the C3 plant Arabidopsis thaliana, are similarly fast to open and close. We identified and cloned the guard cell rectifying outward K+ channel (GROK) of Gynandropsis and showed that GROK is preferentially expressed in stomatal guard cells. GROK is homologous to the Arabidopsis guard cell K+ channel GORK and, expressed in oocytes, yields a K+ current consistent with that of Gynandropsis guard cells. Complementing the Arabidopsis gork mutant with GROK promoted K+ channel gating and K+ flux, increasing stomatal kinetics and yielding gains in water use efficiency and biomass with varying light, especially under water limitation. Our findings demonstrate the potential for engineering a C4 K+ channel into guard cells of a C3 species, and they speak to the puzzle of how C4 species have evolved mechanisms that enhance water use efficiency and growth under stress.
LACCASE35 enhances lignification and resistance against Pseudomonas syringae pv. actinidiae infection in kiwifruit
Authors: Li Yawei , Zhang Dongle , Wang Xiaojie , Bai Fuxi , Li Rui , Zhou Rongrong , Wu Shunyuan , Fang Zemin , Liu Wei , Huang Lili , Liu Pu
Published: January 2025

Kiwifruit bacterial canker, a highly destructive disease caused by Pseudomonas syringae pv. actinidiae (Psa), seriously affects kiwifruit (Actinidia spp.) production. Lignin deposition in infected cells serves as a defense mechanism, effectively suppressing pathogen growth. However, the underlying process remains unclear. In this study, we determined that Psa infection leads to a significant increase in S-lignin accumulation in kiwifruit. The S/G ratio in lignin was higher in a Psa-resistant cultivar than in a Psa-sensitive cultivar. Furthermore, kiwifruit laccase 35 (AcLac35), encoding an enzyme in the lignin biosynthesis pathway with characteristic laccase activity, showed tissue-specific expression in plants and was upregulated following infection by Psa. Overexpressing AcLac35 in kiwifruit leaves resulted in greater lignin content than in wild-type leaves, leading to the formation of thicker cell walls, and also activated plant–pathogen interactions and MAPK pathways, thereby enhancing resistance against Psa infection. Yeast 1-hybrid assays, dual-LUC reporter assays, electrophoretic mobility shift assays, and transient injection experiments indicated that SQUAMOSA PROMOTER-BINDING PROTEIN-LIKE 9 (AcSPL9) can bind to the AcLac35 promoter, thereby positively regulating its expression. Moreover, overexpression of AcSPL9 increased lignin accumulation in kiwifruit leaves, enhancing resistance to Psa, while virus-induced gene silencing of AcSPL9 expression reduced this resistance. Our findings reveal the function of AsSPL9-AcLac35 in kiwifruit, providing insight into enhancing resistance against Psa in kiwifruit.
Loss of PRICKLE1 leads to abnormal endometrial epithelial architecture, decreased embryo implantation, and reduced fertility in mice
Authors: Roberts Emily R , Bhurke Aishwarya V , Ganeshkumar Sornakala , Gunewardena Sumedha , Arora Ripla , Chennathukuzhi Vargheese M
Published: January 2025

Successful embryo implantation requires coordinated changes in the uterine luminal epithelium, including structural adaptations, apical–basal polarity shifts, intrauterine fluid resorption, and cellular communication. Planar cell polarity proteins, essential for cell organization, are understudied in the context of uterine physiology and implantation. PRICKLE proteins, components of PCP, are suggested to play critical roles in epithelial polarization and tissue morphogenesis. However, their function in the polarized unicellular layer of endometrial epithelium, which supports embryo implantation, is unknown. We developed an endometrial epithelial-specific knockout of mouse Prickle1 using Lactoferrin-iCre to investigate its role in uterine physiology. Prickle1 ablation in the endometrial epithelium of mice resulted in decreased embryo implantation by gestational day 4.5, leading to lower fertility. 3D imaging of the uterus revealed abnormal luminal folding, impaired luminal closure, and altered glandular length in mutant uteri. Additionally, we observed decreased aquaporin-2 expression, disrupted cellular architecture, and altered E-cadherin expression and localization in the mutant uterine epithelium. Evidence of epithelial–mesenchymal transition was found within luminal epithelial cells, further linking PRICKLE1 loss to uterine pathologies. Furthermore, altered polarity of cell division leading to incomplete cytokinesis and increase in binuclear or multinucleated cells suggests a crucial role for PRICKLE1 in the maintenance of epithelial architecture. Our findings highlight PRICKLE1's critical role in the planar cell polarity pathway within the uterus, revealing its importance in the molecular and cellular responses essential for successful pregnancy and fertility.
Multi-toric geometries with larger compact symmetry
Authors: Madsen Thomas Bruun , Swann Andrew
Published: January 2025

We study complete, simply connected manifolds with special holonomy that are toric with respect to their multi-moment maps. We consider the cases where there is a connected non-Abelian symmetry group containing the torus. For $ \mathrm{Spin}(7) $-manifolds, we show that the only possibility are structures with a cohomogeneity-two action of $ T^{3} \times \mathrm{SU}(2) $. We then specialize the analysis to holonomy G2, to Calabi-Yau geometries in real dimension six and to hyperKähler four-manifolds. Finally, we consider weakly coherent triples on $ \mathbb{R} \times \mathrm{SU}(2) $, and their extensions over singular orbits, to give local examples in the $ \mathrm{Spin}(7) $-case that have singular orbits where the stabilizer is of rank one.
Financing Infrastructure in the Shadow of Expropriation
Authors: Acharya Viral V , Parlatore Cecilia , Sundaresan Suresh
Published: January 2025

We examine the optimal financing of infrastructure when governments can expropriate rents from private sector firms that manage infrastructure. While private firms need incentives to implement projects well, governments need incentives to limit expropriation. This double moral hazard limits the willingness of outside investors to fund infrastructure projects. Optimal financing contracts involve government guarantees to investors against project failure to incentivize the government to agree not to expropriate, thus improving private sector incentives and project quality. The contract also reflects several other features prevalent in infrastructure financing in practice, among which are government coinvestment, tax subsidies, and development rights. (JEL D82, G30, G32, G38, H20, H54)
Birthing parents’ neural response to infant cry: moderating effects of oxytocin and perceived childhood care
Authors: Grande Leah Ariana , Xie Yun , Zagoory-Sharon Orna , Watamura Sarah Enos , Yeh Tom , Feldman Ruth , Kim Pilyoung
Published: January 2025

Individuals who perceive the caregiving they received from their parents as more caring tend to bond better with their infants and show more sensitive parenting behaviors. Early caregiving experiences are also related to differences in the functions of hormonal systems, including the oxytocinergic system. The current study examined how perceptions of childhood maternal care relate to parenting behaviors, oxytocin levels, and neural responses to infant stimuli. Perceived childhood maternal care was measured using the Parental Bonding Instrument (PBI) for 54 first-time birthing parents. Salivary oxytocin and observations of parenting behaviors were assessed during parent–infant play at 3.5 months postpartum. Neural activation while listening to infant cry was measured with fMRI. More positive perceptions of childhood maternal care and higher oxytocin were interactively related to greater anterior cingulate activation to own infant’s cry. Higher oxytocin levels were associated with reduced left cuneus activation in response to own infant’s cry when compared with control cry and matched noise. Findings suggested that positive memories of childhood caregiving may have protective functions for birthing parents with high oxytocin levels during the early postpartum period, a time when parents need to manage increased stress and form an exclusive bond with their baby.
Effect of beta-agonist type and timing of Experior feeding on calculated cumulative ammonia gas emissions, live growth performance, and carcass outcomes, and objective tenderness outcomes of feedlot steers
Authors: Wendler Wilsey M , Davis Michael S , Koers Walter C , Rincker Phillip J , Pyatt Nathan A , Lucherk Loni W , Lawrence Ty E
Published: January 2025

Our objective was to compare beta-agonist feeding strategies and evaluate Experior (EXP) with added days on feed (DOF) for live growth performance and carcass outcomes. Steers (n = 2,517; initial BW = 336 ± 23 kg) were allocated to 36 pens in a randomized, complete-block design and assigned to 1 of 6 treatments. Treatments were negative control (no beta-ligand; CON), Optaflexx (ractopamine hydrochloride, 300 mg·head−1·day−1 for 35 d; OPT), and Experior (lubabegron fumarate, 36 mg·head−1·day−1 for 56 d + 4 d removal; 0EXP) with all three treatments fed for 198 d. Remaining treatments were fed EXP for same duration as 0EXP, but total DOF were adjusted by −14 d (−14EXP), +14 d (+14EXP) and +28 d (+28EXP). Statistical analyses were conducted using mixed models; treatment was the fixed effect, block was a random effect, means were separated with the Tukey-Kramer adjustment, and contrasts were calculated to test linear or quadratic effects of EXP across DOF. No treatment differences (P ≥ 0.72) were observed for daily dry matter intake. Calculated cumulative ammonia (NH3) gas emissions (CCAGE) expressed either as total NH3 emitted (g) or NH3 emitted per kg of BW or HCW was reduced (P < 0.01) by 5.6–8.5%, 5.1–10.7%, and 6.3–13.6%, respectively for 0EXP, +14EXP and +28EXP compared to CON. Carcass ADG of 0EXP steers was 6.8% greater (P < 0.01) than CON, which had similar (P ≥ 0.10) ADG to OPT, +14EXP, and +28EXP steers. Carcass G:F of 0EXP steers was improved 5.0% compared to CON (P = 0.01) and was not different (P ≥ 0.10) from OPT, −14EXP or +14EXP steers. Hot carcass weight of 0EXP, +14EXP, or +28EXP steers was 14–37 kg heavier (P < 0.01) than CON, which did not differ (P = 0.81) from OPT. Steers fed EXP had 1.15–2.5% point increase (P < 0.01) in dressed yields. Longissimus muscle area was 4.03–6.23 cm2 larger (P < 0.01) in steers fed EXP compared to CON, which tended to differ (P = 0.08) from OPT. Marbling score was 31–39 points lower (P ≤ 0.02) for −14EXP compared to CON and OPT, whereas 0EXP tended (P = 0.09) to differ from CON and +14EXP and +28EXP were similar (P ≥ 0.28) to CON and OPT. Slice shear force values were 20.1% greater (P < 0.02) for +14EXP compared to CON, whereas 0EXP tended (P = 0.09) to be greater and +28EXP, −14EXP and OPT were similar (P ≥ 0.28) to CON. This study illustrates EXP decreased CCAGE and increased HCW with minimal quality changes when fed the last 56 d on feed.
The Fusarium graminearum Effector Protease FgTPP1 Suppresses Immune Responses and Facilitates Fusarium Head Blight Disease
Authors: Darino Martin , Jaiswal Namrata , Darma Reynaldi , Kroll Erika , Urban Martin , Xiang Youhuang , Srivastava Moumita , Kim Hye-Seon , Myers Ariana , Scofield Steven R. , Innes Roger W. , Hammond-Kosack Kim E. , Helm Matthew
Published: January 2025

Most plant pathogens secrete effector proteins to circumvent host immune responses, thereby promoting pathogen virulence. One such pathogen is the fungus Fusarium graminearum, which causes Fusarium Head Blight (FHB) disease on wheat and barley. Transcriptomic analyses revealed that F. graminearum expresses many candidate effector proteins during early phases of the infection process, some of which are annotated as proteases. However, the contributions of these proteases to virulence remains poorly defined. Here, we characterize a F. graminearum endopeptidase, FgTPP1 (FGSG_11164), that is highly upregulated during wheat spikelet infection and is secreted from fungal cells. To elucidate the potential role of FgTPP1 in F. graminearum virulence, we generated FgTPP1 deletion mutants (ΔFgtpp1) and performed FHB infection assays. Deletion of FgTPP1 reduced the virulence of F. graminearium as assessed by spikelet bleaching. Infection with wild-type F. graminearum induced full bleaching in about 50% of the spikes at 10-11 days post infection, while this fraction was reduced to between 18 and 27% when using ΔFgtpp1 mutants. Transient expression of green fluorescent protein (GFP)-tagged FgTPP1 revealed that FgTPP1 localizes, in part, to chloroplasts and attenuates chitin-mediated activation of mitogen-activated protein kinase (MAPK) signaling, reactive oxygen species production, and cell death induced by an autoactive disease resistance protein when expressed in planta. Notably, the FgTPP1 protein is conserved across the Ascomycota phylum, suggesting it may be a core effector among ascomycete plant pathogens. These properties make FgTPP1 an ideal candidate for decoy substrate engineering, with the goal of engineering resistance to FHB.
Novel inflammatory markers in intracerebral hemorrhage: Results from Olink proteomics analysis
Authors: Hu Ziliang , Chen Siqi , Zhang Enhao , Wei Liangzhe , Wang Jieyi , Shang Qing , Gao Xiang , Huang Yi
Published: January 2025

Inflammation is a crucial factor in intracerebral hemorrhage (ICH) pathophysiology, but specific inflammatory biomarkers in ICH patients remain unclear. This study aimed to identify novel circulating inflammatory biomarkers for improved ICH prediction and diagnosis. We profiled expression levels of 92 cardiovascular disease related proteins in plasma from 26 matched ICH patients and controls using Olink technology. Differentially expressed proteins were validated using ELISA and RT‐qPCR in a second matched cohort. Receiver operating characteristic (ROC) curves evaluated how well the diagnostic tests performed. The study identified 18 inflammatory‐related proteins with significantly different expression levels between ICH patients and controls. These proteins participate in critical biological processes and pathways, such as the regulation of inflammatory mediator secretion, cell death, immune cell proliferation and differentiation, pathogen response, and PI3K‐Akt and JAK–STAT pathways. Notably, we discovered for the first time that Kidney Injury Molecule‐1 (KIM1) is significantly upregulated in the plasma of ICH patients, suggesting its potential as a predictive and diagnostic biomarker for ICH. Validation results from ELISA and RT‐qPCR showed that Interleukin‐6 (IL‐6), Pentraxin 3 (PTX3), KIM1, and Galectin‐9 (Gal‐9) concentrations were markedly increased in the blood plasma and white matter of individuals with ICH. ROC analysis showed that the combined marker of IL‐6, PTX3, KIM1 and Gal‐9 had a high diagnostic efficacy (AUC = 0.941). This study identified a novel biomarker panel (IL‐6, PTX3, KIM1, Gal‐9) for ICH diagnosis. KIM1 upregulation in ICH patients is a novel finding, further investigation is needed into its expression and function in ICH.
Betaine‐homocysteine methyltransferase attenuates liver ischemia–reperfusion injury by targeting TAK1
Authors: Liu Xudong , Shi Jihua , Wu Min , Gao Jie , Zhang Yi , Guo Wenzhi , Zhang Shuijun
Published: January 2025

Liver ischemia–reperfusion (IR) injury is a common complication following liver surgery, significantly impacting the prognosis of liver transplantation and other liver surgeries. Betaine‐homocysteine methyltransferase (BHMT), a crucial enzyme in the methionine cycle, has been previously confirmed the pivotal role in hepatocellular carcinoma, and it has also been demonstrated that BHMT inhibits inflammation, apoptosis, but its role in liver IR injury remains unknow. Following I/R injury, we found that BHMT expression was significantly upregulated in human liver transplant specimens, mice and hepatocytes. Utilizing BHMT knockout mice, we established an in vivo model of liver IR injury, and with BHMT knockout and overexpression AML12 cell lines, we created an in vitro hypoxia–reoxygenation model. Our findings reveal that BHMT deficiency exacerbates liver IR injury, leading to increased reactive oxygen species, apoptosis and inflammation, whereas BHMT overexpression mitigates these effects. We observed that BHMT inhibits the c‐Jun N‐terminal kinase (JNK)/p38 signaling pathway in liver IR injury by interacting with TAK1 and inhibiting its activity. The application of 5z‐7‐ox, a TAK1 inhibitor, reversed the worsening of liver IR injury and the activation of the JNK/p38 pathway associated with BHMT deficiency. These results demonstrate that BHMT protects against liver IR injury by targeting TAK1 and inhibiting the JNK/p38 signaling pathway. Our findings suggest that BHMT may be a promising therapeutic target for preventing liver IR injury.
WFDC3 sensitizes colorectal cancer to chemotherapy by regulating ATM/ATR kinase signaling pathway
Authors: Yang Xinying , Weng Kai , Xing Pu , Chen Jiangbo , Hao Hao , Liu Tianqi , Song Tongkun , Qiao Xiaowen , Hou Yifan , Chen Jie , Ran Yumeng , Song Lin , Chen Bo , Yang Hong , Wang Zaozao , Di Jiabo , Jiang Beihai , Su Xiangqian
Published: January 2025

Chemoresistance is an ongoing challenge for colorectal cancer (CRC) that significantly compromises the anti‐tumor efficacy of current drugs. Identifying effective targets or drugs for overcoming chemoresistance is urgently needed. Our previous study showed that WFDC3 served as a tumor suppressor that hindered CRC metastasis. However, the function of WFDC3 in chemotherapy remains unknown. Here, we found that high WFDC3 expression in CRC patients treated with oxaliplatin was associated with a better prognosis. Concordantly, overexpression of WFDC3 significantly increased sensitivity to oxaliplatin in CRC cells, whereas knocking down WFDC3 led to oxaliplatin resistance. In addition, WFDC3 promoted oxaliplatin‐mediated suppression of tumor growth in vivo. Subsequently, we found that WFDC3 could enhance oxaliplatin‐induced DNA damage through inhibiting ATM/ATR signaling. WFDC3 knockdown showed the opposite effects. Moreover, a combination treatment of oxaliplatin and inhibitors for ATM or ATR partially reversed chemoresistance to oxaliplatin in CRC cells with low WFDC3 expression. Our results demonstrate that WFDC3 is possibly a biomarker for increasing oxaliplatin sensitivity in CRC by modulating ATM/ATR kinase signaling. Thus, a combination of oxaliplatin with an ATM or ATR inhibitor is a potential treatment option for improving CRC outcome.
Maternal exposure to bisphenol A induces congenital heart disease through mitochondrial dysfunction
Authors: Guo Yafei , Li Bowen , Yan Yu , Zhang Nanjun , Shao Shuran , Yang Lixia , Ouyang Lixue , Wu Ping , Duan Hongyu , Zhou Kaiyu , Hua Yimin , Wang Chuan
Published: January 2025

Congenital heart disease (CHD) represents a major birth defect associated with substantial morbidity and mortality. Although environmental factors are acknowledged as potential contributors to CHD, the underlying mechanisms remain poorly understood. Bisphenol A (BPA), a common endocrine disruptor, has attracted significant attention due to its widespread use and associated health risks. This study examined the effects of maternal BPA exposure on fetal heart development in a murine model. The findings indicated that high‐dose BPA exposure resulted in fetal growth restriction, myocardial wall thinning, and ventricular septal defects. Transcriptomic analysis revealed downregulation of genes associated with mitochondrial energy synthesis and cardiomyocyte development following high‐dose BPA exposure. Functional assays demonstrated that high‐dose BPA exposure impaired mitochondrial respiration reduced ATP production, disrupted mitochondrial membrane potential, and increased intracellular reactive oxygen species levels in fetal cardiomyocytes. These results elucidate the detrimental effects of BPA on fetal heart development and mitochondrial function, providing insights into potential mechanisms linking environmental chemical exposure to CHD.
Enhancing Research Education Through PhD and DNP Collaboration: Scoping Review and Case Study
Authors: Thomas Rachel McMahan , Shapiro Sandra D.
Published: January 2025

AIM

This article presents details about the literature on challenges and strategies for DNP-PhD nurse collaborations. A secondary aim is to present a case study about a BSN research course co-created by the authors, who are PhD and DNP nurses.

BACKGROUND

Compared to the well-established role of the PhD-prepared nurse, the role of the doctor of nursing practice (DNP) is in its infancy. Collaboration between DNP and PhD faculty offers tremendous value to students.

METHOD

A scoping review of the literature and case study was performed.

RESULTS

Collaborations between PhD and DNP nurses are beneficial. Our case study of a course combining PhD and DNP perspectives resulted in enhanced learning experiences.

CONCLUSION

Collaborations between PhD and DNP nurses can be easily integrated into academic and clinical settings. Frequent opportunities for PhD and DNP collaborations across all levels of nursing education and practice are needed.
Impact of under-assisted ventilation on diaphragm function and structure in a porcine model
Authors: Capdevila Mathieu , Pensier Joris , De Jong Audrey , Jung Boris , Beghin July , Laumon Thomas , Aarab Yassir , Deffontis Lucas , Sfara Thomas , Cuny Ambre , Carr Julie , Molinari Nicolas , Le Guennec Jean-Yves , Raynaud Fabrice , Matecki Stefan , Brochard Laurent , Lacampagne Alain , Jaber Samir
Published: January 2025

Background:

Long-term controlled mechanical ventilation (CMV) in intensive care unit (ICU) induces ventilatory-induced-diaphragm-dysfunction (VIDD). The transition from CMV to assisted mechanical ventilation is a challenge that requires clinicians to balance over-assistance and under-assistance. While the effects of over-assistance on the diaphragm are well known, we aimed to assess the impact of under-assistance on diaphragm function and structure in piglet model with pre-existing VIDD (after long-term CMV) or without VIDD (short-term CMV).

Methods:

Twenty-two Large-White female piglets were anesthetized, ventilated, and separated into two groups: a VIDD group (n=10) with long-term 72-hour CMV, and a no-VIDD group (n=12) with short-term 2-hour CMV. After sedation reduction at the end of CMV period, each piglet was switched to under-assisted ventilation for 2 hours. Diaphragm function (supramaximal diaphragm pressure-generating capacity assessed by negative tracheal pressure after transvenous phrenic nerve stimulation) and diaphragm structure (mini-invasive in vivo biopsies) were assessed before and after under-assisted ventilation.

Results:

In VIDD group, supramaximal diaphragm pressure-generating capacity decreased by 22% from 69.9±12.7 to 54.9±19.7 cmH2O (p=0.04) after 72 hours of CMV evidencing VIDD, then dropped by a further 29% from 54.9±19.7 to 38.9±15.5 cmH2O (p<0.01) after 2 hours of under-assisted ventilation. Diaphragm pressure-generating capacity remains stable from 55.3±22.7 to 58.2±24 cmH2O (p=0.24) in no-VIDD group. Diaphragm structure showed sarcomeric injuries increase from 13±10% to 24±19% (p<0.01) and lipid droplets decrease from 14±8% to 11±6% (p=0.03) of the total micrograph area after 2 hours of under-assisted ventilation in the VIDD group. Sarcomeric injuries and lipid droplets accounted respectively for 17±16% and 2±3% of the total micrograph area after under-assisted ventilation in the no-VIDD group.

Conclusions:

In this porcine model, a short two-hour exposure of under-assisted ventilation induces impairment of diaphragm function with damage to the diaphragm structure in ICU condition with pre-existing VIDD.
Prevalence of Stroke and Associated Factors in a Middle-aged and Older Chinese Population: A Cross-sectional Study
Authors: Guo Juan , Guo Qingmin , Chen Yuzhen , Zou Jinmei
Published: January 2025

Objective:

Elderly individuals are at high risk for stroke. With China transitioning into an aging society, it is essential to implement measures to prevent stroke in the middle-aged and elderly. This study aimed to investigate the prevalence and associated factors of stroke in middle-aged and older Chinese individuals using national survey data from the China Health and Retirement Longitudinal Study.

Methods:

This cross-sectional study used data from the 2015 China Health and Retirement Longitudinal Survey. Participants without complete data on stroke and its associated factors—including demographics, health behaviors, and disease-related factors—were excluded. Independent samples t-test and χ
2 test were used to examine differences in associated factors between the stroke and non-stroke groups. Variables with P-values ≤0.1 in all univariate comparisons were included in the final binary logistic regression model to identify the independent factors associated with stroke.

Results:

A total of 11,969 participants were included in this study. The prevalence of stroke in middle-aged and older individuals in China was 2.170%. The most significant factors associated with stroke included smoking (odds ratio (OR): 1.471, 95% confidence interval (CI): 1.132–1.913), alcohol consumption (OR: 0.548, 95%CI: 0.405–0.743), nap time ≥30 min and <60 min (OR: 0.502, 95%CI: 0.296–0.851), nap time ≥60 min and <90 min (OR: 0.703, 95%CI: 0.505–0.978), hypertension (OR: 3.310, 95%CI: 2.515–4.357), dyslipidemia (OR: 1.874, 95%CI: 1.446–2.428), and diabetes (OR: 1.424, 95%CI: 1.052–1.927).

Conclusion:

This study reveals a high prevalence of stroke in middle-aged and older people in China. Several factors, including smoking, alcohol consumption, nap time, hypertension, dyslipidemia, and diabetes, were identified as significant associated factors of stroke prevalence in this population. These findings can inform the development of stroke prevention strategies and health planning for middle-aged and older adults and provide insights for future research.
Increased Cardiac Troponin T May Be a Marker of Worsening Skeletal Myopathy in Inclusion Body Myositis
Authors: Fu Zhiqing , Zhang Xiujin
Published: January 2025

Previous studies have reported elevated cardiac troponin T (cTnT) in patients with inclusion body myositis due to skeletal myopathy. Although the trends of cTnT have been reported in some cases, the onset of elevation has barely been reported. In this case, elevated cTnT in a patient diagnosed with inclusion body myositis is discussed. The routine laboratory tests of a 68-year-old male patient showed a positive cTnT test. Eight months later, he developed symptoms of myasthenia gravis. Subsequently, after a series of examinations, the patient was diagnosed with inclusion body myositis. Despite a transient decrease in cTnT levels following intravenous immunoglobulin treatment, the levels rapidly rebounded and continued to rise, suggesting continued progression of skeletal muscle damage in inclusion body myositis. It was concluded that the elevated cTnT was due to re-expression of cTnT in the damaged skeletal muscles of inclusion body myositis. This suggests that dynamic monitoring of cTnT levels in inclusion body myositis patients may predict the progression of myositis and promote timely treatment.
Comparison of 2-Bag Method With Serial Bag Method for Treatment of Pediatric Diabetic Ketoacidosis
Authors: Hone Kristina , Agus Michael S. D. , Russ Christiana M. , Manzi Shannon , Berbert Laura , Engstrand Shannon , Reed Mary Poyner
Published: January 2025

Background

There have been 2 primary methods of intravenous fluid administration for diabetic ketoacidosis (DKA) treatment described in the literature: the serial bag method and the 2-bag method.

Objectives

This study will assess the clinical outcomes and workflow efficiency after a transition in practice from the serial fluid method to the 2-bag method for pediatric DKA.

Methods

This was a retrospective chart review of pediatric DKA patients 18 years or younger, 1 year before and after the transition was conducted. After exclusion criteria, 94 patients in the serial bag method group and 100 patients in the 2-bag method group remained. Variables included patient demographics, laboratory values, and duration of therapy.

Results

Patients achieving physiologic resolution of DKA had a median duration of 8.7 hours using the serial bag method and 7.5 hours using the 2-bag method (P = .193). Duration of DKA pharmacologic therapy had median values of 11.6 and 12.7 hours, between the serial bag and 2-bag method, respectively (P = .203). The 2-bag method resulted in faster workflow efficiency per bag for intravenous fluids, with a median duration of 35.5 minutes compared with 44.5 minutes using the serial bag (P = .025). Episodes of hypokalemia (P = .010) and hyperchloremia (P = .002) with the 2-bag method were significantly more frequent.

Discussion

Duration of DKA pharmacologic therapy and that of physiologic DKA were not statistically different between methods. Workflow efficiency improved with the 2-bag method. Further studies are needed to address potential electrolyte disturbances with the 2-bag method.
Prevalence and predictors of genitourinary syndrome of menopause: a population-based study in middle-aged Brazilian women
Authors: Bevilacqua Mariana Rosa Ribeiro , Costa-Paiva Lucia , Pedro Adriana Orcesi
Published: January 2025

Objective

This study aimed to determine the prevalence and predictors of genitourinary syndrome of menopause (GSM) in Brazilian women.

Methods

A cross-sectional population-based household survey was conducted among 749 women aged 45 to 60 years. The dependent variable was the presence of GSM, which was assessed using a pretested structured questionnaire. The independent variables included sociodemographic data, health-related habits and morbidities, self-perception of health, and gynecological background.

Results

The mean age of the participants was 52.5 ± 4.4 years, and the mean age of menopause was 46.4 ± 6.2 years. GSM was prevalent in 51.4% of the women. The most prevalent symptoms were dyspareunia (35%), daily vaginal dryness (25.1%), and intercourse vaginal dryness (24%). Poisson regression analysis demonstrated that global GSM was associated with having a partner, topical estrogen treatment (TET), depression/anxiety, and rheumatological diseases. The genital symptoms of GSM were related to peri/postmenopausal status, TET, multimorbidity, sexual activity, and the absence of vaginal birth. Factors associated with GSM urinary symptoms were negative self-perception of health, having at least one vaginal birth, depression/anxiety, and rheumatological diseases. Sexual symptoms were associated with having a partner, using TET, depression/anxiety, and rheumatic disease. GSM affected the lives of 42.8% of the women to some degree, and 43% discussed their symptoms with their gynecologists.

Conclusions

GSM was prevalent in half of the women in this study, and several factors were associated with its presence. These results highlight the compelling need to understand these factors, improve diagnoses, and increase access to treatment.
The complementary effects of formal and informal budgetary performance feedback on doctor-managers' responsibilities
Authors: Paolini Manuela , Raucci Domenico , Morandi Federica , Di Vincenzo Fausto
Published: January 2025

Background

The reforms that have affected public health care organizations have changed the tasks and responsibilities of physicians heading operational units, who have become doctor-managers. This hybridization makes doctor-managers vulnerable to role ambiguities, with possible dysfunctional effects on their managerial behaviors and performance. The enhancement of different sources of budgetary performance feedback (BPF) and perceived organizational support (POS) can help them reconcile their managerial and clinical professional domains.

Purpose

Rooted in psychology-based budgeting research, this study aimed to show the role of doctor-managers' perceptions of BPF by examining the complementary effects of formal and informal BPF on POS and their satisfaction with the budget-holder role.

Methodology/Approach

We collected self-reported data by administering questionnaires to a sample of doctor-managers from Italian public health care organizations. The hypotheses were tested using a linear regression model, clustered at the hospital level. Mediation analysis was used to test the mediating effects of POS.

Results

Findings showed that formal and informal BPF perceptions positively influenced POS and satisfaction with the budget-holder role. Further, POS mediated the BPF–role satisfaction link.

Conclusion

The study adds to the limited research on the individual-level benefits of perceived formal and informal BPF as complementary mechanisms for improving doctor-managers' attitudes toward the budget-holder role.

Practice Implications

Top management and controllers should develop budgeting practices that consider the psychological factors related to the complementary functioning of formal and informal BPFs. These factors may support doctor-managers in meeting their responsibilities as budget holders and mitigate role ambiguities.
Dissatisfaction after implantation of extended depth-of-focus intraocular lenses
Authors: Wanten Joukje C. , Bauer Noël J.C. , Berendschot Tos T.J.M. , van den Biggelaar Frank J.H.M. , Nuijts Rudy M.M.A.
Published: January 2025

Purpose:

To evaluate the symptoms, etiology and treatment of patient dissatisfaction after extended depth-of-focus (EDOF) intraocular lens (IOL) implantation.

Setting:

University Eye Clinic, Maastricht University Medical Center, the Netherlands

Design:

Retrospective case series.

Methods:

For this study, all medical records of patients who received an EDOF IOL from July 2020 to July 2022 were reviewed. Patients were included if they had reported any dissatisfaction after surgery. The main outcome parameters were reasons for dissatisfaction (subjective complaints) and the presumed etiology of the complaints.

Results:

Out of 202 patients (354 eyes) who underwent EDOF IOL implantation, 83 eyes (22.8%) of 52 dissatisfied patients were included. Blurred vision was the predominant complaint, reported in 78 eyes (94%). Photic phenomena were reported in 21 eyes (25.3%), with 16 eyes (76.2%) experiencing coexisting blurred vision. The major etiologies for dissatisfaction in this cohort were residual ametropia (51.8%), dry eye disease (26.5%), and posterior capsular opacification (12.0%). Treatments were administered to 85.5% of the eyes, including interventions such as artificial tears, spectacles, or refractive surgery enhancement. A small number of patients (n=12; 5.9%) remained dissatisfied despite intervention.

Conclusion:

Based on this real-world data study, dissatisfaction following EDOF IOL implantation can be effectively identified and treated in most cases.
Symptoms in Persons With Either Active or Inactive Crohn‘s Disease Are Agnostic to Disease Phenotype
Authors: Bernstein Charles N. , Nugent Zoann , Panaccione Remo , Marshall Deborah A. , Kaplan Gilaad G. , Dieleman Levinus A. , Vanner Stephen , Graff Lesley A. , Otley Anthony , Jones Jennifer , Buresi Michelle , Murthy Sanjay , Borgaonkar Mark , Bressler Brian , Bitton Alain , Croitoru Kenneth , Sidani Sacha , Fernandes Aida , Moayyedi Paul
Published: January 2025

Background:

We aimed to examine the relationship between disease symptoms and disease phenotype in a large Canadian cohort of persons with Crohn’s disease (CD).

Methods:

Adults (n=1515) with CD from 14 Canadian centers participated in the Mind And Gut Interactions Cohort (MAGIC) between 2018 and 2023. Disease activity was measured using the 24-item IBD Symptom Inventory-Short-Form (IBDSI-SF). We compared the symptoms commonly associated with active versus inactive disease, and explored symptoms patterns in relation to disease phenotype, based on the Montreal Classification. To assess psychological status the Generalized Anxiety Disorder-7 and Patient Health Questionnaire-9 were used.

Results:

The mean disease duration was 15.6±11.8 years. The 5 most common symptoms were similar for those with active disease, although at higher prevalence (89% to 98%) versus those with inactive disease (47% to 79%), and included fatigue, diarrhea, gas, bloating, and urgency. The intensity of symptoms was higher in those with active than inactive IBDSI-SF scores. The rank order and relative distribution of the symptoms and intensity of the symptoms reported were similar between those with different disease phenotypes B1, B2, and B3 and L1, L2, and L3. Persons with active IBDSI-SF had a higher prevalence of anxiety (24.6%) and depression (38.2%) versus persons with inactive IBDSI-SF (6.3% and 8%, respectively)

Conclusions:

Individuals with CD with active and inactive disease by IBDSI, experience similar symptoms, but the prevalence of symptoms and their intensity is greater in persons with active IBDSI. Persons with inactive IBDSI report many symptoms. There was no difference in symptom reporting by disease behavior or location.