bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between female waist-hip ratio and live birth in patients undergoing in vitro fertilization: a retrospective cohort study
Authors: Ye Mingming , Yang Yingying , Cai Chenting , Li Zhen , Qiu Andong , He Jia , Ma Jing , Bukulmez Orhan , Norman Robert J. , Teng Xiaoming , Chen Miaoxin
Published: February 2025

Background

Maternal obesity is associated with adverse pregnancy outcomes. It negatively affects IVF/ICSI outcomes and offspring health. However, it is unclear whether waist-hip ratio (WHR) has an impact on outcomes of in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) cycles.

Methods

A retrospective cohort study screened 943 patients who underwent IVF/ICSI treatment between February and June 2020 in Shanghai, China, and 828 patients were finally included in the analyses. The body weight, height, waist circumference and hip circumference were measured before ovarian stimulation, and their IVF/ICSI outcomes were followed up. The cut-off point of WHR was determined by the area under the receiver operating characteristic (ROC) curve. Live birth rate from the first embryo transfer cycle was the primary outcome. The secondary outcomes included cumulative live birth, miscarriage rate and birthweight.

Results

Women with relatively high WHR (≥0.783) showed lower live birth rate (adjusted odds ratio (aOR): 0.657, 95%CI: 0.466-0.926), lower cumulative live birth rate (aOR: 0.580, 95%CI: 0.413-0.814), and higher miscarriage rate (aOR=2.865, 95%CI: 1.300-6.316) as compared with those with low WHR (<0.783), independently of BMI. Joint WHR and BMI analyses showed that, compared with the reference group (those with low WHR and normal weight), those with high WHR and normal BMI had lower live birth rate (aOR=0.653, 95%CI: 0.447-0.954) and cumulative live birth rate (aOR=0.600, 95%CI: 0.413-0.872), and higher miscarriage rate (aOR=2.865, 95%CI: 1.229-6.676), Whereas the patients with both high WHR and high BMI only showed a significant lower cumulative live birth rate (aOR=0.612, 95%CI: 0.404-0.926). Moreover, there was no significant association between BMI and pregnancy outcomes, or between maternal WHR and birth weights.

Conclusions

Our results demonstrated that higher WHR was associated with lower fecundability in women undergoing IVF/ICSI cycles, independently of BMI. Interestingly, the adverse effects of central obesity were more evident in patients with lower BMI. Thus WHR appears to be a better predictor of female fertility treatment outcomes as compared with BMI.
Characterization of the fate of primary and re-precipitated silver nanoparticles in lake water model systems
Authors: Rao Sarayu , Gao Xiaoyu , Ghoshal Subhasis
Published: February 2025

The increasing use of silver nanoparticles (nAg) in products and associated releases to the environment necessitates a thorough understanding of the environmental fate and transformations of these potentially toxic nanomaterials to inform environmental risk assessments. Herein, the physical and chemical transformations of nAg in natural lake water samples were investigated. Lake water systems containing filtered and unfiltered lake water (FLW and UFLW) were spiked with 80 nm polyvinylpyrrolidone-coated nAg (nAgpristine) at 6 μg/L and were maintained under quiescent or mixed conditions in the dark for up to 44 days. Aliquots withdrawn from the water column contained smaller re-precipitated nAg (r-nAg, diameter ∼26 nm) formed by precipitation of Ag+ released by oxidative dissolution of nAgpristine. The number concentrations of r-nAg and nAgpristine were comparable. In FLW, agglomerates of r-nAg and the partially dissolved nAgpristine were formed under quiescent conditions and their settling accelerated after 14 days, but no settling occurred in the mixed systems. In UFLW, heteroagglomerates of r-nAg and the partially dissolved nAgpristine with natural colloids formed and induced sedimentation in both quiescent and mixed systems. A fraction of the r-nAg formed and the larger (>40 nm) or primary n-Ag (comprised of partially dissolved nAgpristine and its agglomerates with r-nAg or itself) were persistent in the water column for several weeks. Under quiescent conditions, more p-nAg remained suspended in FLW (15.7%, relative to number of nAgpristine dosed) than in UFLW (5.9%), whereas more r-nAg persisted in UFLW (2.6%) than in FLW (0.6%). Thus, the size distributions and fractions of nAg persisting in the water column can change significantly depending on water chemistry and mixing conditions.
Case report and literature review: clinical manifestations and treatment of human RelA deficiency
Authors: Wang Chenghao , Wang Wenjie , Hui Xiaoying , Hou Jia , Zhou Qinhua , Li Qifan , Wu Qi , Ni Qi , Wu Bingbing , Sun Jinqiao , Wang Xiaochuan
Published: February 2025

RelA deficiency resulting from mutations in the human RELA gene is a recently identified inborn errors of immunity (IEI). The RELA gene encodes the RelA (p65) protein, one of the five transcription factors of the NF-κB family, which plays a critical role in the regulation of transcriptional programs essential for the development and maintenance of the immune system, skeletal system, and epithelial tissues. RelA deficiency is classified as RelA haploinsufficiency and RelA dominant-negative. The mainly pathogenesis is that impaired NF-κB activation in fibroblasts, which leads to the downregulation of NF-κB-dependent antiapoptotic protein expression and cytokine transcription, renders fibroblasts susceptible to TNF-induced apoptosis. Clinical manifestations of RelA deficiency are typically characterized by recurrent oral ulcers or Behçet’s disease-like manifestations. Since the first report in 2016, only a few dozen cases of RelA deficiency have been documented worldwide. Treatment strategies have not been standardized, with current mainstream approaches primarily involving immunosuppressive therapies, including TNF inhibitors or glucocorticoids. In this study, we report the clinical phenotypes of three patients with RelA deficiency from two families, along with one novel pathogenic mutation (c.1166_1184del, p.Q389fs) in the RELA gene. This expands the spectrum of pathogenic mutations associated with the RELA gene and clinical manifestations of RelA deficiency. Additionally, we provide a comprehensive summary of the genetic phenotypes, clinical characteristics, and treatment strategies of all previously reported cases of RelA deficiency. Our aim is to increase awareness of this rare IEI and to offer insights that may guide its treatment.
Successful treatment with refractory myasthenia gravis that developed after allogeneic hematopoietic stem cell transplantation: two case reports
Authors: Zhang Huili , Wen Yi , Ou Yaotong , Chen Xi , Peng Yu , Lai Mingjun , Mo Wenjian , Wang Honghao
Published: February 2025

Introduction

Myasthenia gravis (MG) is an autoimmune disorder caused by autoantibodies that target the neuromuscular junction, leading to muscle weakness and fatigability. Diagnosis is based on clinical presentation, confirmation of the presence of AChR-Ab, characteristic electromyography findings, and clinical improvement after administration of acetylcholinesterase inhibitors.MG is often associated with thymoma and other autoimmune diseases, but it is rare following allo-HSCT.

Case report

we reports two rare cases of MG after transplantation, including the first case of post-transplantation double-antibody-positive MG. Patient 1 was a 45-year-old woman diagnosed with B-cell acute lymphoblastic leukemia. She underwent haploidentical allo-HSCT from a female donor (5/10 matching human leukocyte antigens [HLAs]) and developed graft-versus-host disease (GVHD) after transplantation. At 42 months after transplantation, the patient developed episodic generalized weakness, dysarthria, dysphagia, and axial weakness. The serum anti-acetylcholine receptor antibodies (AchR-Abs) level was > 20 nmol/L (normal range: < 0.4 nmol/L). She was diagnosed with MG type IIb according to the Myasthenia Gravis Foundation of America classification. At 44 months post-transplantation, the patient began to experience episodic cramps, Electromyography (EMG) revealed a small number of fibrillation potentials with the right thumb extensor and the right anterior tibial muscle in a relaxed state, as well as spastic discharge, considered indicative of cramp–fasciculation syndrome (CFS). Improvement was seen following treatment with carbamazepine. Patient 2 was a 49-year-old man diagnosed with acute myeloid leukemia. He underwent haploidentical allo-HSCT from his son and did not develop GVHD. At 23 months post-transplant, the patient experienced recurrent diplopia, ptosis, axial weakness, and dyspnea. Neostigmine and repetitive nerve stimulation tests were positive, the level of anti-AChR IgG antibodies and MuSK receptor antibodies were positive, leading to a diagnosis of type IVb MG. The symptoms were mostly relieved after rituximab treatment.

Discussion

This article reports two rare cases of MG after transplantation, including the first case of post-transplantation double-antibody-positive MG, and reviews the general clinical characteristics of MG cases after allo-HSCT reported in previous literature. These cases enhance our understanding of MG following transplantation and add to the data on post-transplantation MG.
Disitamab vedotin vs. gemcitabine-cisplatin regimen with immunotherapy: a comparative analysis of efficacy and safety in muscle-invasive bladder cancer
Authors: Zhang Chuanao , Yu Yanhang , Zhou Qi , Ouyang Jun , Zhang Zhiyu
Published: February 2025

Introduction

Muscle-invasive bladder cancer (MIBC) is an aggressive bladder cancer characterized by invasion of the muscular bladder wall, often necessitating a multimodal treatment approach for optimal outcomes. This study aimed to compare the real-world efficacy and safety of disitamab vedotin (RC48), an antibody-drug conjugate (ADC), combined immunotherapy targeting programmed cell death protein-1 (PD-1), against the gemcitabine and cisplatin (GC) regimen with PD-1 immunotherapy in the treatment of MIBC.

Methods

This single-center, retrospective study was conducted at the First Affiliated Hospital of Soochow University and included 38 patients with MIBC treated with either RC48 plus immunotherapy or GC regimen plus immunotherapy, between January 2022 and December 2023. Patients were divided into two groups: the RC48 with immunotherapy (ADC + PD-1) group and the GC regimen with immunotherapy (GC + PD-1) group. Efficacy was evaluated based on their pathological complete response rates (PCRR) and pathological downstaging rates (PDR). Adverse events (AEs) were assessed to compare safety profiles.

Results

Of the 38 patients, 17 were in the ADC + PD-1 group and 21 were in the GC + PD-1 group. The PCRR was significantly higher in the ADC + PD-1 group (82.35%, 14/17) compared to the GC + PD-1 group (47.62%, 10/21; P = 0.043). The PDR was also higher in the ADC + PD-1 group (94.12%, 16/17) than in the GC + PD-1 group (80.95%, 17/21), although the difference was not statistically significant (P = 0.355). No serious allergic reactions or fatal AEs were reported in either group. No Grade 4 AEs were reported, while Grade 3 AEs occurred at a rate of 5.71% in the ADC + PD-1 group and 12.20% in the GC + PD-1 group (P = 0.260).

Conclusion

RC48 combined with immunotherapy demonstrated a significantly higher PCRR compared to the GC regimen with immunotherapy, while maintaining a comparable safety profile. These findings highlight the potential of RC48 combined with immunotherapy as an effective treatment option for MIBC in clinical practice.
Multi-parameter optimizations of elastic chain catenary based on response surface methodology for high-speed railway
Authors: Zhang Zongfang , Zhang Maoyou
Published: February 2025

As train operating speeds increase, the quality of pantograph-catenary current collection deteriorates, sometimes even resulting in contact loss. To ensure stable current collection during high-speed operation, it is crucial to optimize the design parameters of the catenary system. This study employs finite element analysis and constructs a pantograph-catenary coupling model using MSC. Marc software to simulate the coupled motion between the catenary and the pantograph. During the research process, the primary technical challenge was accurately evaluating the comprehensive effects of multi-parameter variations on pantograph-catenary current collection quality. First, we independently analyzed the effects of catenary tension and linear density variations on contact pressure to clarify the mechanisms of individual parameter influences. However, recognizing that multiple parameters might change simultaneously in actual operations, we introduced the Response Surface Methodology (RSM) to deeply explore the combined effects of two parameters on current collection quality. The innovation of this study lies not only in considering the effects of individual parameters but also in systematically analyzing the impact of multi-parameter interactions using RSM. Furthermore, from the perspective of the combined effects of catenary tension and contact wire linear density, we proposed an optimized catenary design scheme for the 500 km/h high-speed train operation scenario. Specifically, by increasing the contact wire tension, reducing the messenger wire tension, and lowering the linear density of the contact wire, we can significantly improve pantograph-catenary current collection quality, thereby providing robust support for the safe and stable operation of high-speed railways. In conclusion, this study addresses key technical challenges in multi-parameter optimization and proposes a practical optimization scheme with significant application value, offering important references for the design and optimization of high-speed railway catenary systems.
Prevalence and contributing factors of depression among women with infertility in low-resource settings: a systematic review and meta-analysis
Authors: Tadesse Shimelis , Kumsa Henok , Kitil Gemeda Wakgari , Chereka Alex Ayenew , Gedefaw Getnet , Chane Fiker , Mislu Esuyawkal
Published: February 2025

Background

Depressive symptoms are the most common manifestations of psychiatric disorders among women with infertility. In low-resource settings, the overall prevalence and contributing factors of depressive symptoms among women with infertility remain unknown.

Objectives

To estimate the prevalence and contributing factors of depression among women with infertility in low-resource settings.

Methods

A review was conducted using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The PubMed, MEDLINE, Google Scholar, and Cochrane databases were used to identify eligible studies published up to 30 November 2024. Three authors independently extracted the data. Studies that reported depression among women with infertility were included in this review. The data were analyzed with STATA version 14, and a meta-analysis was conducted using a random-effects model. Publication bias and heterogeneity were assessed via Eager’s tests and I2. Subgroup and sensitivity analyses were performed to identify the potential source/s of heterogeneity. A p-value of 0.05 was declared as statistically significant. The findings were synthesized and presented using texts, tables, and forest plots with measures of effect and 95% confidence interval (CI).

Results

Seventeen published cross-sectional studies that met the inclusion criteria with a total of 3,528 women with infertility were selected for this study. The pooled prevalence of depression among women with infertility was 48.77% (95% CI (35.86, 61.67). Good functioning family {OR 0.71 [95% CI (0.51, 0.97), I2: 0.00%]}, good husband support {OR 0.52 [95% CI (0.34, 0.79), I2: 0.00%]}, primary infertility {OR 2.55 [95% CI (1.36, 4.79), I2: 68.53%]}, history of divorce {OR 4.41 [95% CI (2.11, 9.24), I2: 0.00%]}, and duration of infertility lasting more than 10 years {OR 6.27 [95% CI (2.74, 14.34), I2: 15.26%]} were statistically significant.

Conclusion

Depression was high among women with infertility in low-resource settings such as Africa compared to those in high-income countries, men, and pregnant mothers. Good functioning family, good husband support, primary infertility, history of divorce, and duration of infertility lasting more than 10 years were statistically associated. Therefore, African countries and the stakeholders in collaboration with mental health experts and gynecological care providers should address these problems in order to reduce or prevent depression among women with infertility.

Systematic Review Registration

PROSPERO (ID: CRD42024516458).
Social participation patterns and associations with subsequent cognitive function in older adults with cognitive impairment: a latent class analysis
Authors: Li Xin , Feng Haishan , Chen Qingling
Published: February 2025

Background

Social participation (SP) has been associated with cognitive benefits among older adults; however, little is known about SP patterns and their relationships with cognitive function in cognitively impaired populations. This study aimed to identify SP patterns among cognitively impaired older individuals and evaluate their associations with subsequent cognitive function, specifically mental intactness and episodic memory.

Methods

Data were drawn from the China Health and Retirement Longitudinal Study (CHARLS), including 5,673 individuals aged 60 years and older with cognitive impairment from 2015 to 2018. Latent class analysis (LCA) was used to identify SP patterns, and hierarchical linear regression analyses were conducted to examine associations between these patterns and cognitive function.

Results

Four distinct SP patterns were identified: “Offline Social Participation Group” (Class 1), “Intellectual Social Participation Only Group” (Class 2), “Club and Volunteer Activities Group” (Class 3), and “Minimal Social Participation Group” (Class 4). The Class 4 comprised the majority (73%) and exhibited the poorest cognitive outcomes. Compared to the Class 4, Class 2 showed significant improvements in mental intactness (p < 0.001) and episodic memory (p = 0.022), while Class 3 demonstrated significant improvements in mental intactness (p = 0.032) but not episodic memory. Class 1 showed significant improvements in episodic memory (p = 0.023).

Conclusion

This study highlights the cognitive benefits of social participation, particularly intellectual activities, for older adults with cognitive impairment. Targeted interventions promoting SP, especially intellectual activities, are essential to mitigate cognitive decline and improve cognitive resilience in vulnerable populations.
A dual role for pleiotrophin in modulating inflammation and myelination in the presence of chondroitin sulfate proteoglycans after nervous system injury
Authors: Gupta Somnath J. , Churchward Matthew A. , Todd Kathryn G. , Winship Ian R.
Published: February 2025

Chondroitin sulfate proteoglycans (CSPGs), key components of the extracellular matrix and the glial scar that forms around central nervous system (CNS) injuries, are recognized for hindering neuronal regeneration. We previously demonstrated the potential of pleiotrophin (PTN) to induce neurite outgrowth even in the presence of inhibitory CSPGs. The effects of PTN on microglia and oligodendrocytes are not well described. Here, we examined how PTN administration alters the differentiation of oligodendrocyte precursor cells (OPCs) into mature oligodendrocytes in the presence of CSPGs using in vitro cell culture model. Moreover, we explored the effects of PTN on the inflammatory activity of microglia with and without inflammatory stimulation (IFN-γ) in a CSPG-rich environment. The data showed that the CSPG matrix inhibited the differentiation of OPCs into mature oligodendrocytes. PTN induced dose-dependent differentiation of OPCs into mature oligodendrocytes, with an optimal effect at 10 nM PTN. Moreover, PTN modified the immunological response of microglia in the presence of CSPGs, with reduced proinflammatory activity that was further reduced by PTN administration, in contrast to the increased release of matrix metalloproteinases (MMP 9). However, when IFN-γ-activated microglia were treated with PTN, proinflammatory signaling was stimulated at higher PTN concentrations (10 nM and 100 nM). Overall, our results indicate that PTN can overcome the inhibitory effect of CSPGs on the differentiation of OPCs into oligodendrocytes and can modulate inflammation mediated by CSPGs from microglia. Collectively, these findings demonstrate that PTN can effectively counteract the inhibitory effects of CSPGs on the differentiation of OPCs into mature oligodendrocytes while also modulating microglial responses to reduce proinflammatory activity and increase MMP-9 release. Thus, PTN has great potential to improve remyelination and neuroprotective strategies in the treatment of demyelinating diseases or any injury.
Differences in lower limb co-contraction calculations vary clinical interpretation of aquatic treadmill walking in typically developing and children with cerebral palsy
Authors: Harrington Joseph W. , Knarr Brian A. , Dutt Vivek , Kingston David C.
Published: February 2025

Objective

The purposes of this study were to (1) investigate muscle co-contraction during aquatic (Wet) and conventional (Dry) treadmill walking at various speeds in typically developing (TD) and children with cerebral palsy (CP) and (2) explore how the clinical interpretation of co-contraction, using co-contraction indices (CCI), may vary depending on the method employed.

Methods

Fifteen TD children (30 limbs, 7 M | 8F, 11.3 ± 4.1 yrs., 1.46 ± 0.18 m, 44.2 ± 16.8 kg) and 10 children with CP (20 limbs, 6 M | 4F, 13.1 ± 3.5 yrs., 1.54 ± 0.18 m, 53.2 ± 26.2 kg, 7 GMFCS I and 3 II) participated in this study. Muscle activity of the tibialis anterior (TA), rectus femoris (RF), medial gastrocnemius (MG), and semitendinosus (ST) was recorded during three 3-min walking trials on a Dry treadmill followed by a Wet treadmill. Muscle co-contraction was calculated using three common CCI calculation methods for the RF/ST and TA/MG muscle pairings. Separate linear mixed-effects models examined the influence of population (TD vs. CP), walking speed (Slow, Normal, Fast), and treadmill environment (Dry vs. Wet) on CCI for each equation and muscle pairing.

Results

CCIUnnithan and CCIRudolph demonstrated that aquatic treadmill walking reduced muscle co-contraction in TD (p < 0.001) and CP (p < 0.012) populations for the RF/ST muscle pairing. Additionally, CCIUnnithan and CCIRudolph showed significant differences between speeds in both environments (p < 0.001) except for the Slow-Normal comparison in the aquatic treadmill (p > 0.423). All methods had a significant CCI reduction in the TA/MG muscle pairing for both populations. For the RF/ST muscle pairing, CCIF&W showed that only TD children had lower muscle co-contraction in the aquatic treadmill (p = 0.023). CCIF&W also showed no speed effect for the muscle pairings.

Conclusion

This study shows the potential of aquatic treadmill walking to reduce muscle co-contraction; however, caution is recommended as clinical implications can vary due to the computation method. Future studies should aim to report values from multiple methods to account for the variability within methods and validation of results.
Gait impairments in patients with bilateral vestibulopathy and chronic unilateral vestibulopathy
Authors: Boutabla Anissa , Revol Rebecca , Carvalho Marys Franco , Grouvel Gautier , Corre Julie , Cugnot Jean-François , Cavuscens Samuel , Ranieri Maurizio , Zhu Meichan , McCrum Christopher , van de Berg Raymond , Armand Stéphane , Fornos Angélica Pérez , Guinand Nils
Published: February 2025

Vestibular deficits often lead to unsteady gait, affecting quality of life and increasing fall risk. This study aimed to identify gait impairments in chronic vestibulopathy. Ten patients with bilateral vestibulopathy (BV), 10 patients with chronic unilateral vestibulopathy (UV), and 10 healthy participants (HS) participated. Spatio-temporal parameters were computed during walking at various self-selected walking speeds (slow, comfortable, and fast) using motion capture system with additional assessment usingclinical gait tests [functional gait assessment (FGA), tandem walk (TW), Timed Up and Go test (TUG)], and symptom severity [Dizziness Handicap Inventory (DHI)] were assessed and compared between the three groups. BV and UV patients showed significantly slower walking speeds, shorter step lengths, and broader step widths compared to HS, but similar cadence. Significant differences were also seen in stance phase, double and single support phases at comfortable and slow speeds, but not at fast speed. BV patients, but not UV patients, had worse FGA scores than HS, reflecting their reported difficulties in specific tasks requiring greater postural control. Tandem walk performance was lower in BV patients compared to the other groups, whereas there was no significant differences in TUG scores. Cluster analysis revealed two distinct clusters: one with all HS and most UV patients (70%), and another with most BV patients and 30% of UV. Overall, this study highlights how altered vestibular function impacts gait outcomes. These findings can aid clinicians in evaluating gait in patients with vestibular deficits and monitoring rehabilitation interventions.
Maternal oral supplementation with Saccharomyces boulardii I-1079 during gestation and early lactation impacts the early growth rate and metabolic profile of newborn puppies
Authors: Bendahmane Ilyas , Garrigues Quentin , Apper Emmanuelle , Mugnier Amélie , Svilar Ljubica , Martin Jean-charles , Chastant Sylvie , Meynadier Annabelle , Mila Hanna
Published: February 2025

Nutritional programming is a manipulation of fetal and neonatal development through maternal feeding. In humans and pigs, maternal yeast supplementation was demonstrated as a promising approach to positively to modulate newborns' health. This study aimed to investigate the effects of Saccharomyces cerevisiae var. boulardii CNCM I-1079 (SB) supplementation in pregnant and lactating bitches on the newborns' early growth rate (EGR, between birth and 2 days of life), metabolic profiles, and the association between both of them. A total of 17 female dogs and their 81 puppies were included. From day 28 of gestation until the end of the study, bitches were divided into two groups, one of which received orally 1.3 × 109 colony forming units of live yeast per day. Puppies from mothers receiving the live yeast were defined as the SB group (n = 40) and the others were defined as the placebo group (n = 4 1). For each puppy, EGR was calculated, and blood and urine samples were collected at D2 for metabolome analysis using liquid chromatography-mass spectrometry (LCMS). Puppies from the SB group presented higher EGR compared with the placebo group (12% vs. 7%; p = 0.049). According to the Sparse Partial Least Squares Discriminant Analysis (sPLS-DA), both urine and serum metabolome profiles were significantly different between the two groups with a total of 29 discriminating metabolites in urine and serum. Fourteen of them were implicated in the nitrogen metabolism pathway including, gamma-aminobutyrate, 3-methyl-l-histidine and xanthosine (less abundant in SB compared with placebo group, all p < 0.05), adenine, aspartate and proline (more abundant in SB compared with placebo group, all p < 0.05). Metabolic pathways pointed to proline synthesis, a crucial component in collagen synthesis and osteoarticular system development. Urinary proline abundance was positively correlated with EGR (r = 0.45; p < 0.001). These findings highlight the potential benefits of maternal supplementation with SB promoting early neonatal growth, essential for the neonatal survival, through nitrogen metabolism orientation.
The relationship between the ratio of non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol (NHHR) and both MASLD and advanced liver fibrosis: evidence from NHANES 2017–2020
Authors: Li Juyi , Kou Chunjia , Chai Yuwei , Li Yuchen , Liu Xue , Zhang Li , Zhang Haiqing
Published: February 2025

Background

The non-HDL-C to HDL-C ratio (NHHR) is a dependable lipid marker linked to atherosclerotic traits. This study examines the potential relationship between NHHR and both metabolic dysfunction-associated steatotic liver disease (MASLD) and advanced liver fibrosis.

Methods

This study investigated the relationship between NHHR levels and both MASLD and advanced liver fibrosis using data from the 2017–2020 National Health and Nutrition Examination Survey (NHANES) in the United States. First, we conducted a baseline characteristics analysis of the population based on NHHR quartiles. Second, we employed multivariable weighted linear regression models to examine the associations between NHHR and MASLD, as well as advanced liver fibrosis. Third, we utilized restricted cubic splines (RCS) to assess potential non-linear relationships. Fourth, we performed subgroup analyses. Finally, ROC curve analysis was conducted to evaluate the effectiveness of NHHR.

Results

In the main analysis, this study included a total of 9,864 participants. Following multivariable logistic regression and comprehensive adjustments, elevated NHHR levels in the Q3 and Q4 groups were significantly linked to MASLD, with odds ratios of 1.59 (95% CI: 1.20–2.11) and 1.83 (95% CI: 1.40–2.39), respectively (P for trend < 0.0001). Elevated NHHR levels in the Q2 and Q3 groups remained significantly linked to a decreased risk of advanced liver fibrosis, with odds ratios of 0.61 (95% CI 0.40–0.94, P = 0.03) and 0.64 (95% CI 0.47–0.89, P = 0.01), respectively. RCS analysis revealed a U-shaped nonlinear association between NHHR and both MASLD (P = 0.000; P for nonlinear = 0.029) and advanced liver fibrosis (P = 0.0001; P for nonlinear = 0.000). In the subgroup analysis, we found that this relationship was significant only in certain subgroups. The ROC curve analysis revealed that NHHR exhibited the best predictive performance for diagnosing MASLD based on the fatty liver index (FLI). The optimal cutoff point for NHHR in predicting MASLD using FLI was determined to be 2.476, with sensitivity and specificity values of 0.589 and 0.698, respectively.

Conclusion

NHHR may serve as a predictive marker for MASLD and advanced liver fibrosis, highlighting its potential significance in risk assessment and prevention strategies.
Challenges in diagnosing and managing sarcomatoid urothelial carcinoma of the renal pelvis: a case report
Authors: Lei Jian , Zhao Wei , He Tao , Huang Hui , Jian Huayong , Zhang Mei , Luo Xike , Gong Xiaochuan , Wang Yan
Published: February 2025

Sarcomatoid urothelial carcinoma of the renal pelvis is an extremely rare malignant tumor with a high risk of recurrence and metastasis and a poor prognosis. This case reports a 61-year-old male patient with renal pelvic sarcomatoid urothelial carcinoma who developed extensive lymph node metastasis 26 days after posterior laparoscopic radical nephrectomy for renal carcinoma, and the patient died on the 45th postoperative day, with the cause of death being advanced malignancy of the tumor. This case highlights the rapid progression of sarcomatoid urothelial carcinoma, and sarcomatoid variants should be identified as early as possible, with active multidisciplinary adjuvant therapy and closer follow-up when feasible. Retrospective analysis of this patient’s treatment regimen and admission provides lessons for recognizing and aggressively managing this rare and fatal variant of urothelial carcinoma.
Explainable AI in medical imaging: an interpretable and collaborative federated learning model for brain tumor classification
Authors: Mastoi Qurat-ul-ain , Latif Shahid , Brohi Sarfraz , Ahmad Jawad , Alqhatani Abdulmajeed , Alshehri Mohammed S. , Al Mazroa Alanoud , Ullah Rahmat
Published: February 2025

Introduction

A brain tumor is a collection of abnormal cells in the brain that can become life-threatening due to its ability to spread. Therefore, a prompt and meticulous classification of the brain tumor is an essential element in healthcare care. Magnetic Resonance Imaging (MRI) is the central resource for producing high-quality images of soft tissue and is considered the principal technology for diagnosing brain tumors. Recently, computer vision techniques such as deep learning (DL) have played an important role in the classification of brain tumors, most of which use traditional centralized classification models, which face significant challenges due to the insufficient availability of diverse and representative datasets and exacerbate the difficulties in obtaining a transparent model. This study proposes a collaborative federated learning model (CFLM) with explainable artificial intelligence (XAI) to mitigate existing problems using state-of-the-art methods.

Methods

The proposed method addresses four class classification problems to identify glioma, meningioma, no tumor, and pituitary tumors. We have integrated GoogLeNet with a federated learning (FL) framework to facilitate collaborative learning on multiple devices to maintain the privacy of sensitive information locally. Moreover, this study also focuses on the interpretability to make the model transparent using Gradient-weighted class activation mapping (Grad-CAM) and saliency map visualizations.

Results

In total, 10 clients were selected for the proposed model with 50 communication rounds, each with decentralized local datasets for training. The proposed approach achieves 94% classification accuracy. Moreover, we incorporate Grad-CAM with heat maps and saliency maps to offer interpretability and meaningful graphical interpretations for healthcare specialists.

Conclusion

This study outlines an efficient and interpretable model for brain tumor classification by introducing an integrated technique using FL with GoogLeNet architecture. The proposed framework has great potential to improve brain tumor classification to make them more reliable and transparent for clinical use.
The role of myeloid-derived suppressor cells in children
Authors: Brauner Jordan , Wilt Anna , Montgomery Christopher P. , Bline Katherine
Published: February 2025

Myeloid-derived suppressor cells (MDSC) were first recognized over twenty years ago as a key immunomodulatory cell population. Since their initial identification, a growing body of literature points to the importance of MDSC as a heterogeneous, immunosuppressive cell population and as a therapeutic target in adults with cancer. MDSC are potent suppressors of T cells and Natural Killer (NK) cells and can be helpful or harmful to the host depending on the pathophysiology. For example, MDSC are beneficial in pregnancy and prevent spontaneous abortion by promoting maternal-fetal tolerance. Increased MDSC are also associated with improved outcomes in patients with graft vs. host disease by decreasing T cell-driven inflammation. However, MDSC can also be harmful and are known to be pathologic in adults with cancer and chronic infections by promoting tumor escape and impairing pathogen clearance, respectively. Despite the widespread recognition of the importance of MDSC and their immune suppression effects in adults, much less is known regarding the role of MDSC in children. Research investigating MDSC in children lags significantly behind adult studies. In fact, while over 5,000 publications on PubMed discuss MDSC in immune regulation, fewer than 50 of these publications focus specifically on their role in children. This review aims to summarize the existing literature on the role of MDSC in children and identify important directions for future research, including targeting these cells in the pediatric population to improve clinical outcomes.
Case Report: Anti-interferon-γ autoantibodies in an adolescent with disseminated Talaromyces marneffei and mycobacterial co-infections
Authors: Li Bingkun , Li Tiantian , Huang Qihua , Mo Nanfang , He Xiaojuan , Jiang Zhiwen , Li Xiuying , Huang Xiaolu , Zhang Xinyu , Cao Cunwei
Published: February 2025

Background

Anti-interferon-γ autoantibodies (AIGAs) are associated with adult-onset immunodeficiency syndrome, which makes individuals susceptible to intracellular pathogen infections. However, AIGAs are rarely reported in adolescents.

Case presentation

We report a 13-year-old Chinese boy who presented with fever, cough, and enlarged cervical lymph nodes. Blood cultures yielded Mycobacterium abscessus, and Talaromyces marneffei (TM) was cultured from pericardial effusion. Whole exome sequencing revealed no pathogenic variants. Notably, high levels of neutralizing AIGAs were detected in the patient's serum. After receiving treatment for Mycobacterium abscessus and antifungal therapy for TM, the patient showed significant improvement. However, at the 19-month follow-up, the patient developed a Mycobacterium asiaticum infection.

Conclusion

This case highlights the importance of screening for AIGAs in pediatric patients with disseminated TM or NTM infections. Prolonged treatment and continuous follow-up remains crucial for managing pediatric patients with AIGAs.
Discovery of highly potent and novel LSD1 inhibitors for the treatment of acute myeloid leukemia: structure-based virtual screening, molecular dynamics simulation, and biological evaluation
Authors: Hong Ye , Wang Yuting , Hao Ziyi , Zhang Xingxia , Si Yejun , Lin Guoqiang , Zhang Shurong , Niu Miao-Miao , Yang Xiaotian , Zhang Yanming
Published: February 2025

Acute myeloid leukemia (AML) is a highly aggressive hematological malignancy with a significant unmet clinical need for new therapeutic agents. Lysine-specific demethylase 1 (LSD1), a key regulator of leukemia stem cell self-renewal, has emerged as a promising epigenetic target for AML treatment. Herein, we employed an innovative multi-step integrated screening protocol, encompassing pharmacophore modeling, docking screening, molecular dynamics simulation, and biological evaluation, to identify novel LSD1 inhibitors. This comprehensive approach led to the discovery of six potent LSD1 inhibitors (we named these inhibitors LTMs 1–6), with LTM-1 exhibiting the most pronounced inhibitory effects on LSD1 (IC50 = 2.11 ± 0.14 nM) and the highest selectivity for LSD1 over LSD2 (>2370-fold). Notably, LTM-1 demonstrated outstanding antitumor activity both in vitro and in vivo. In vitro, LTM-1 showed potent anti-proliferative effects against LSD1-addicted MV-4-11 leukemia cells (IC50 = 0.16 ± 0.01 μM). In vivo, LTM-1 treatment significantly reduced tumor growth in MV-4-11 xenografted mice. Moreover, LTM-1 did not induce significant changes in liver and kidney function indices, suggesting a favorable safety profile. These results indicate that LTM-1 is a highly promising preclinical candidate for AML treatment, offering a new strategy for the development of more effective and selective LSD1 inhibitors.
In vitro and in vivo characterization of oridonin analogs as anti-inflammatory agents that regulate the NF-κB and NLRP3 inflammasome axis
Authors: Ou Huiping , Wu Zhanpan , Ning Jinhua , Huang Qiufeng , Wang Wancun , Yang Guochun , Zhou Yingxun , Hou Anguo , Li Peng , Chen Lingyun , Jin Wen Bin
Published: February 2025

Introduction

A series of oridonin hybrids were synthesized and evaluated for anti-inflammatory potential, focusing on their ability to inhibit NO production in RAW264.7 cells and their therapeutic prospects for NLRP3-driven disorders.

Methods

Anti-inflammatory activity was assessed by measuring NO inhibition in LPS-stimulated RAW264.7 cells. The most active compound, 4c, was further analyzed using ELISA and WB to evaluate its effects on inflammatory proteins (p-NF-κB, p-IκB, NLRP3, IL-6, IL-1β, COX-2, iNOS). In vivo efficacy was tested in a murine acute lung injury model, with RT‒qPCR and WB used to assess inflammatory markers in lung tissues. Molecular docking predicted 4c’s binding mode with NLRP3, while RNA-seq and RT‒qPCR identified differentially expressed genes.

Results

Compound 4c significantly inhibited NO production and suppressed key inflammatory proteins in vitro. In vivo, it alleviated acute lung injury, reduced IL-6 and TNF-α mRNA levels, and inhibited NLRP3, p-NF-κB, and IL-6 protein expression. Docking suggested covalent binding to NLRP3. RNA-seq revealed 4c upregulated Trdc, Stfa2, and Gsta2 while downregulating Spib, Csf2, and Nr4a1.

Discussion

Compound 4c demonstrates potent anti-inflammatory effects via NLRP3 pathway inhibition and modulation of inflammatory genes. These findings highlight oridonin hybrids, particularly 4c, as promising candidates for NLRP3-driven inflammatory disorders, warranting further investigation.
Does the occurence of homostyly necessarily accompany the breakdown of heteromorphic incompatibility system?
Authors: Zhao Jing , Kuliku Laiziti , Zhang Aiqin , Jiao Fangfang , Ren Dengfu
Published: February 2025

Introduction

Heterostyly is a genetic polymorphism that facilitates precise pollen transfer through reciprocal herkogamy. The loss or variation of reciprocal herkogamy is usually accompanied by the breakdown of heteromorphic incompatibility system. Homostyly, which is characterized by self-compatibility and same stigma-anther height is a common floral morph in the variation and evolution of heterostyly. Limonium aureum is a distylous species distributed in the desert of northwest China, in which a floral morph with the same stigma-anther height (H-morph) widely distributed in the natural populations, resembling classical homostyly. The aim of this study was to clarify whether the occurrence of H-morph is also accompanied by the breakdown of heteromorphic incompatibility system, and the relationship between the H-morph and long-styled-/shortstyled-morph (L-/S-morph).

Methods

The floral morphs composition and frequency, heterostylous syndrome, pollinators and visiting efficiency were investigated in five natural populations of L. aureum based on field observation, artificial control pollination experiment and so on.

Results and conclusion

All populations were composed of L-, S- and H-morphs, except for ATS population with only H-morph, and there were significant differences in flower size parameter, fruit set, and degree of pollination limitation, while no differences among morphs within population. However, each population demonstrated dimorphic pollen-stigma morphology and a strict heteromorphic incompatibility system, especially ATS population, in which they were compatible between morphs with heteromorphic pollen-stigma morphology, regardless of the reciprocal herkogamy, and vice versa. It is speculated that the H-morph in different populations may be at different stages of heterostylous evolution. The ATS population may be a dimorphic population without reciprocal herkogamy which is in the stage before distyly formation, while the other 4 populations may be dimorphic populations with significant variation in reciprocal herkogamy which is in the stage after distyly formation. The H-morph may be caused by stigma-anther separation shortening of L- and S-morph in other 4 populations. These phenomenons that the variation of floral morph is independent of physiological incompatibility breakdown, as well as the coexistence of populations from different origins and evolutionary stages within the same species have been reported for the first time in the Plumbaginaceae.
A study of the effect of question feedback types on learning engagement in panoramic videos
Authors: Huang Guan , Zhang Haohua , Zeng Jingsheng , Chen Wen
Published: February 2025

Introduction

The immersive and interactive nature of panoramic video empowers learners with experiences that are infinitely close to the real environment and increases the use of imagination in learners’ knowledge acquisition. Studies have shown that embedding question feedback in traditional educational videos can effectively improve learning. However, little research has been conducted on embedding question feedback in panoramic videos to explore what types of question feedback effectively improve the dimensions of learners’ learning engagement and yield better learning experiences and learning effects.

Methods

This study embedded questions with feedback within panoramic videos by categorizing feedback into two types: simple feedback and elaborated feedback. Using eye tracking, brainwave meters, and subjective questionnaires as measurement tools, this study investigated which type of question feedback embedded in panoramic videos improved various dimensions of learner engagement and academic performance. Participants (n = 91) were randomly assigned to the experimental group (simple feedback, elaborated feedback) or the control group (no feedback).

Results

The results of the study showed that (1) the experimental group significantly improved in cognitive engagement, behavioral engagement, and emotional engagement compared to the control group. When the precision of feedback information was greater, the learner’s behavioral engagement was greater; however, the precision of feedback information did not significantly affect cognitive and emotional engagement. (2) When the feedback information was more detailed, the learners’ academic performance was better.

Discussion

The findings of this study can support strategic recommendations for the design and application of panoramic videos.
Paranormal belief and conspiracy theory endorsement: variations in adaptive function and positive wellbeing
Authors: Dagnall Neil , Denovan Andrew , Drinkwater Kenneth Graham , Escolà-Gascón Álex
Published: February 2025

Recent studies report that paranormal belief and conspiracy theory endorsement are differentially related to factors allied to positive wellbeing (e.g., meaning in life and coping behaviours). Since these findings derive from correlational studies using cross sectional designs, researchers need to undertake further investigation to establish outcome robustness. Accordingly, the present study used a multiple time point design. Respondents (N = 1,158) completed measures on three occasions, three months apart. While a strong positive association was found between paranormal belief and conspiracist theory endorsement, path analysis revealed divergent relationships with positive wellbeing outcomes. Specifically, paranormal belief predicted greater levels of positive wellbeing over time (meaning in life and social identity), whereas conspiracy theory endorsement predicted only social identity. Consideration of mediation effects revealed that paranormal belief prognosticated greater presence of meaning in life via links with active coping and positive outlook. Additionally, avoidant coping positively mediated the paranormal belief-search for meaning in life relationship. Conspiracy theory endorsement predicted greater social identity via avoidant coping. Findings indicated that paranormal belief and conspiracy theory endorsement were differentially related to positive wellbeing outcomes. Regarding paranormal belief, the construct was concomitantly attendant with passive and active psychological functions. The association with avoidant coping suggested that in some circumstances supernatural credence enables believers to avert attention from problems.