bluuebunny/crossref_metadata_2025 huggingface dataset:
Hypertensive disorders of pregnancy in Hunan Province, China, 2012–2022
Authors: Zhou Xu , Wu Yinglan , Chen Xiaoying , Jiang Yurong
Published: December 2024

Objective

To explore the relationship between hypertensive disorders of pregnancy (HDP) and adverse pregnancy outcomes and explore the risk factors for HDP.

Methods

Data were obtained from the Maternal Near-Miss Surveillance System in Hunan Province, China, 2012–2022. Chi-square trend tests (χ2trend) were used to determine trends in prevalence by year. Unadjusted odds ratios (uORs) were used to examine the association between HDP and adverse pregnancy outcomes. Multivariate logistic regression analysis (method: Forward, Wald, α = 0.05) and adjusted odds ratios (aORs) were used to identify risk factors for HDP.

Results

Our study included 780,359 pregnant women, and 38,397 women with HDP were identified, with a prevalence of 4.92% (95% CI 4.87–4.97). The prevalence of preeclampsia-eclampsia, gestational hypertension, chronic hypertension, and chronic hypertension with superimposed preeclampsia was 2.28% (95% CI 2.25–2.31), 2.04% (95% CI 2.00–2.07), 0.43% (95% CI 0.41–0.44), and 0.18% (95% CI 0.17–0.19), respectively. From 2012 to 2022, the prevalence of HDP increased from 3.11 to 7.39%, showing an upward trend (χ2trend = 2220.88, p < 0.01). HDP was associated with the following adverse pregnancy outcomes: maternal deaths (uOR =4.05), maternal near-miss (uOR =6.37), preterm birth (uOR =2.51), stillbirth and neonatal death (uOR =1.45), low birthweight (uOR =4.37), abruptio placentae (uOR =4.45), uterine atony (uOR =1.49), retained placenta (uOR =1.54), puerperal infections (uOR =2.14), abdominal surgical site infections (uOR =2.50), urinary tract infections (uOR =1.60), upper respiratory tract infections (uOR =1.75), heart disease (uOR =2.76), embolism (uOR =2.66), liver disease (uOR =1.25), anemia (uOR =1.38), diabetes mellitus (uOR =2.35), renal disease (uOR =4.66), and pulmonary disease (uOR =4.70, p < 0.05). Results of multivariate logistic regression analysis showed risk factors for HDP: maternal age > 30 years (aOR > 1, p < 0.05), gravidity > = 4 (aOR =1.10, 95% CI 1.05–1.14), primipara (aOR > 1, p < 0.05), and previous cesarean sections (aOR =1.27, 95% CI 1.24–1.31).

Conclusion

The prevalence of HDP was relatively high in Hunan Province. HDP was associated with many adverse pregnancy outcomes. Advanced maternal age, high gravidity, primipara, and previous cesarean section were risk factors for HDP.
Compartmental analysis of retinal vascular parameters and thickness in myopic eyes using SS-OCTA
Authors: Zeng Chen , Tang Chong , Tan Yixin , Liu Juxian , Shi Kai , Li Qi
Published: December 2024

Background

This study aimed to comprehensively explore the thickness and topographic distributions of retinal vessel alterations of different myopic eyes by using swept-source OCT angiography (SS-OCTA).

Methods

One hundred myopes were included in this observational cross-sectional study. All participants underwent a series of ocular examinations of biometrical parameters, including spherical equivalent refraction (SER), axial length (AL), intraocular pressure (IOP), curvature radius (CR), and others. Retinal parameters like vessel density (VD) of different compartments of papillary and peripapillary sectors were measured by SS-OCTA, respectively. Two sample-independent T-test was applied to identify intraocular differences in retinal biometrical indicators between groups, and correlation analysis was used to explore potential relationships between AL/CR ratio and some ocular variables.

Results

For high myopic participants, they exhibited a lower vessel density, a lower small vessel density, and a lower flow area, especially in the superficial layer and the nerve fiber layer (RNFL), along with a thinner superficial layer, RNFL and retina. More alterations were proved in nasal peripapillary sectors in high myopes. We also explored their hidden relationship with AL/CR ratio. We found that in non-high myopes, the thickness of the whole retina, RNFL and the superficial layer were all negatively correlated with AL/CR ratio in the papillary and peripapillary zone. In contrast, the vessel density and flow area of several vessel layers were positively correlated. However, there wasn’t so much significance found in high myopic eyes.

Conclusion

Retinal vessel microstructure was more easily affected in highly myopic eyes, especially in superficial blood vessels, and compartmental analysis showed that alterations in nasal peripapillary sectors were more evident. Additionally, we highlighted hidden correlations between AL/CR ratio and blood flow characteristics of specific vascular layers, which could serve as sensitive biometrical indicators of early retinal damages.
High prevalence and plasmidome diversity of optrA-positive enterococci in a Shenzhen community, China
Authors: Fu Yulin , Deng Zhaoju , Shen Yingbo , Wei Weizhou , Xiang Qiumei , Liu Zhiyang , Hanf Kunning , Huang Suli , Lv Zexun , Cao Tingting , Peng Changfeng , Zhang Rong , Zou Xuan , Shen Jianzhong , Schwarz Stefan , Wang Yang , Liu Dejun , Lv Ziquan , Ke Yuebin
Published: December 2024

Background

The emergence of optrA, which can confer resistance to phenicols and oxazolidinones in Enterococcus spp., poses a growing public health threat.

Methods

102 optrA-positive enterococci (OPEs) including various species were isolated from feces of 719 healthy volunteers in a Shenzhen community, China. Antimicrobial susceptibility of these isolates was tested. Whole-genome sequencing and bioinformatics analysis were performed to characterize molecular epidemiology of OPEs.

Results

Compared to optrA-negative enterococci (ONEs), antimicrobial resistance (linezolid, florfenicol, doxycycline, erythromycin and ciprofloxacin) and presence of antimicrobial resistance genes (ARGs) (fexA, cat, tet(M), erm(A), erm(B) and etc) were higher in OPEs. Phylogenetic analysis revealed that high similarly (19–338 SNPs) was observed between the optrA-positive E. faecalis from community and the strains from patients, animals, and environment. In 102 OPEs, the optrA gene was detected on the chromosome (n = 36), on plasmids (n = 62), or both (n = 4). A diverse range of optrA-carrying plasmid types was identified. The rep9-plasmid replicons were widely detected in E. faecalis (44/66), whereas repUS1-plasmid replicons were widely identified in other enterococcal species (7/66). Most of all ARGs harbored by isolates were co-existed on optrA-carrying plasmids, suggesting that the acquisition of optrA-carrying plasmids will pose a greater threat to public health. Notably, the pAD1 (rep9 family) + DOp1-type plasmids should receive more attention for the transfer of optrA given their high prevalence (36.36%), high number of co-located ARGs with optrA (83.87% of total ARGs) and presence in multiple sources. Tn6674, IS1216E, ISEnfa1 and ISEnfa5 are related to the transfer of chromosomal and plasmids-derived optrA, respectively. The bcrABDR gene cluster, fexA, and erm(A) were frequently identified surrounding optrA and may be transferred with optrA via IS1216E or ISEnfa1.

Conclusion

The transfer of optrA gene is related to a variety of mobile elements (including plasmids, insertion sequences, transposons), which will promote the horizontal transfer of optrA. Moreover, many ARGs co-exist with optrA and could co-transfer with optrA. The acquisition of OPEs and optrA-carrying plasmids will pose a greater threat to public health and should be obtained more attention, especially optrA-positive E. faecalis and pAD1 + DOp1-type plasmids.
Immunomodulatory peptides: new therapeutic horizons for emerging and re-emerging infectious diseases
Authors: Chatterjee Debolina , Sivashanmugam Karthikeyan
Published: December 2024

The emergence and re-emergence of multi-drug-resistant (MDR) infectious diseases have once again posed a significant global health challenge, largely attributed to the development of bacterial resistance to conventional anti-microbial treatments. To mitigate the risk of drug resistance globally, both antibiotics and immunotherapy are essential. Antimicrobial peptides (AMPs), also referred to as host defense peptides (HDPs), present a promising therapeutic alternative for treating drug-resistant infections due to their various mechanisms of action, which encompass antimicrobial and immunomodulatory effects. Many eukaryotic organisms produce HDPs as a defense mechanism, for example Purothionin from Triticum aestivum plant, Defensins, Cathelicidins, and Histatins from humans and many such peptides are currently the focus of research because of their antibacterial, antiviral and anti-fungicidal properties. This article offers a comprehensive review of the immunomodulatory activities of HDPs derived from eukaryotic organisms including humans, plants, birds, amphibians, reptiles, and marine species along with their mechanisms of action and therapeutic benefits.
Diagnostic performance of biomarkers for differentiating active tuberculosis from latent tuberculosis: a systematic review and Bayesian network meta-analysis
Authors: Jeong Ji Hun , Shim Sung Ryul , Han Sangah , Hwang Inhwan , Ihm Chunhwa
Published: December 2024

Background

PCR and culture tests are used together to confirm the diagnosis of active tuberculosis (TB). Due to the long culture period, if the PCR test is negative, it takes a significant amount of time for the culture result to be available. Interferon-γ release assays (IGRAs), which are widely used to diagnose TB or latent tuberculosis infection (LTBI), cannot effectively discriminate TB from LTBI. The purpose of this study is to analyze the diagnostic performance of various markers for differentiating between TB from LTBI.

Methods

PubMed-Medline, EMBASE, Cochrane Library, and Web of Science were searched up to the end of May 2024, without restrictions on publication date and population. Articles describing the diagnostic value of at least one biomarker for differentiating between TB and LTBI were included. The QUADAS-2 tool was used to assess study quality. Two independent researchers assessed the articles using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The network meta-analysis (NMA) was performed for diagnostic tools of 11 groups used to differentiate TB from LTBI.

Results

Out of 164 identified articles, 159 reports were included in the systematic review and 58 in the meta-analysis. Seventy results from 58 reports accounting for 9,291 participants were included. When measuring interleukin-2 (IL-2) after stimulation with latency antigen, the most significant odds ratio was shown in terms of sensitivity, specificity, positive predictive value and negative predictive value. The values were 9.46, 18.5, 11.30, and 9.61, respectively.

Conclusion

This study shows that the IL-2 level after stimulation with latent antigen is a potential biomarker for differentiating TB from LTBI.

Systematic review registration

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024542996.
Response of Staphylococcus aureus to combination of virulent bacteriophage vB_SauM-515A1 and linezolid
Authors: Abdraimova Narina K. , Shitikov Egor A. , Bespiatykh Dmitry A. , Gorodnichev Roman B. , Klimina Ksenia M. , Veselovsky Vladimir A. , Boldyreva Daria I. , Bogdanova Alexandra S. , Klinov Dmitry V. , Kornienko Maria A.
Published: December 2024

The combined use of lytic bacteriophages with antibiotics is currently being explored as a strategy to enhance the effectiveness of infectious disease therapies, including those caused by Staphylococcus aureus. In this study, we investigated the synergistic potential of bacteriophage vB_SauM-515A1 (Herelleviridae family) and the first-line antibiotic linezolid against the methicillin-resistant S. aureus strain SA0413Rev. A checkerboard assay revealed a significant synergistic effect against planktonic cells (FIC = 0.225): a combination of 1/8 MIC of linezolid and 0.01 MOI of the bacteriophage completely inhibited bacterial growth. However, the impact on biofilm-associated cells depended on the treatment sequence. Sequential administration resulted in antagonism, while simultaneous application demonstrated a synergistic effect, as confirmed through scanning electron microscopy. Transcriptomic analysis of S. aureus SA0413Rev under the combined influence of linezolid (1/4 MIC) and bacteriophage vB_SauM-515A1 (10 MOI) predominantly reflected changes associated with productive bacteriophage infection, including alterations in nucleotide metabolism, activation of prophage regions, and virulence factors. Furthermore, both agents affected energy and carbon metabolism. These findings contribute to the development of combination therapy approaches for infections caused by S. aureus and highlight the importance of optimizing treatment conditions for maximal therapeutic efficacy.
Clinical management and nursing care for patients with tracheostomy following traumatic brain injury
Authors: Mao Xiongyan , Zhou Yuchan , Chen Qiye , Zhang Yelei
Published: December 2024

Tracheostomy is a routine surgical procedure in patients with severe traumatic brain injury, which requires mechanical ventilation to maintain gas exchange and avoid hypoxemia. Inadequate tracheostomy timing, nursing care, and decannulation would lead to a series of complications, such as aggravated pneumonia and prolonged intubation. The effects of early tracheostomy versus late tracheostomy have been explored. And early tracheostomy is more likely associated with shorter hospital stays and fewer complications. But the relevant reports are controversial. A safe and fast tracheostomy decannulation would facilitate the recovery. However, there was a broad variability in the indications and timing of tracheostomy and decannulation. High-quality evidence is subsequently lacking. We conducted this review to address gaps in knowledge regarding the management strategy and nursing protocol in patients with tracheostomy and decannulation following traumatic brain injury. A multidisciplinary tracheostomy team containing nursing care was also discussed to provide the best service to these patients.
Optimal proprioceptive training combined with rehabilitation regimen for lower limb dysfunction in stroke patients: a systematic review and network meta-analysis
Authors: Zheng Kaiqi , Li Li , Zhou Yahui , Gong Xiaokun , Zheng Gangbin , Guo Liang
Published: December 2024

Background

This study aims to evaluate the optimal rehabilitation regimen for lower limb dysfunction in stroke patients by analyzing the effects of proprioceptive training (PT) in combination with different rehabilitation interventions.

Methods

Randomized controlled trials (RCTs) published up to April 23, 2024, were searched from PubMed, Embase, Cochrane Library, Web of Science, CNKI, Wanfang, VIP, and SinoMed. The quality of the included studies was assessed using the Cochrane Risk of Bias tool (ROB 2.0). Network meta-analysis was performed via R studio and STATA 15.0.

Results

A total of 64 RCTs involving 4,084 stroke patients with lower limb dysfunction were included. For balance ability in stroke patients, PT in combination with motor relearning programme (PT + MRP) demonstrated the optimal rehabilitation effect [surface under the cumulative ranking curve (SUCRA) 77.94%]. For lower limb motor function, PT in combination with closed kinematic chain exercises (PT + CKCE) was most effective (SUCRA 88.39%). For walking ability, PT in combination with visual feedback training (PT + VFT) was superior (SUCRA 96.61%). Cluster analysis indicated that PT + CKCE and PT + RT1 were the optimal rehabilitation regimens for lower limb dysfunction in stroke patients.

Conclusion

PT+MRP was the optimal rehabilitation regimen for improving balance ability in stroke patients; PT+CKCE was the best for enhancing lower limb motor function; and PT+VFT was most effective for improving walking ability. Overall, PT+CKCE and PT+RT1 represented the optimal rehabilitation regimens for lower limb dysfunction in stroke patients, while PT+RT1 is most effective within 5 days of stroke onset.

Systematic review registration

https://www.crd.york.ac.uk/PROSPERO/#recordDetailsCRD42024548889, PROSPERO CRD42024548889.
The pivotal role of sleep in mediating the effects of life stressors and healthy habits on allostatic load in mid-life adults
Authors: Buller-Peralta Ingrid , Gregory Sarah , Low Audrey , Dounavi Maria-Eleni , Bridgeman Katie , Ntailianis Georgios , Lawlor Brian , Naci Lorina , Koychev Ivan , Malhotra Paresh , O'Brien John T. , Ritchie Craig W. , Dauvilliers Yves , Muniz-Terrera Graciela
Published: December 2024

Objectives

We assessed the modulation of allostatic load (AL) by engagement in healthy habits and life stressors, mediated through resilience and the perceived influence of the stressors. Sleep was included as third mediator given extensive evidence associating to all the analysed factors.

Methods

Structural equation models to assess the modulation of AL by either traumatic or psychosocial stressors and healthy habits were generated with data from 620 mid-life adults (age 51.3 ± 5.48 years). Model 1 included self-reported life stressors, engagement in cognitive and physical activities, resilience and a pyramid score for diet. In Model 2, self-reported sleep quality was included in the mediation analysis between resilience and perceived stress on AL.

Results

Direct effects of sports and diet on AL, and on resilience by sports were found in all the evaluated models. The modulation of AL by both types of stressors was only revealed in model 2, through indirect effects of perceived influence via sleep quality. An effect of sport habits on AL via resilience was found to be mediated by sleep, and equivalent but opposed effects of perceived influence of stressors and resilience on sleep quality emerged as critical factor for AL modulation.

Conclusion

Our results suggest that sleep plays a pivotal role in the modulation of AL by both life stressors and sport habits, balancing the harmful and protective effects of perceived stress and resilience. The relative weight of one over the other to worsen or improve sleep quality will determine the resulting level of AL.
Case report: A de novo variant of CRMP1 in an individual with a neurodevelopmental disorder
Authors: Liu Juan , Wang Qi , Chen Jia
Published: December 2024

Background

CRMP1 is a key protein involved in brain development.

Methods

We performed genetic testing through whole-exome sequencing (WES) in an individual with a neurodevelopmental disorder.

Results

We identified a de novo heterozygous CRMP1 NM_001014809.3:c.1755del (p.Lys586fs) variant in the affected individual. This mutation was submitted to ClinVar (SCV005196589).

Conclusion

Currently, the CRMP1 gene has no clear disease phenotype association in the Online Mendelian Inheritance in Man (OMIM) database. Our report may provide evidence for an association between the CRMP1 gene and neurodevelopmental disorders (NDDs).
Lactiplantibacillusplantarum HM-P2 influences gestational gut microbiome and microbial metabolism
Authors: Liu Bin , Zhang Zhenzhen , Zhao Junying , Li Xianping , Wang Yaru , Liu Lu , Qiao Weicang , Chen Lijun
Published: December 2024

Introduction

Human milk-derived probiotics are beneficial bacteria that provide gestational health benefits, for both pregnant women and their offspring. The study aims to investigate whether the administration of human milk-derived probiotic L. plantarum HM-P2 could effectively influence gestational health.

Methods

The gestational humanized microbiome model was built by fecal microbiome transplant from gestational women into germ-free (GF) mice.

Results

HM-P2 was successfully planted and increased the top crypt depth of the colon, and microbes such as L. reuteri,Anaerofilum sp. An201, and Gemmiger were up-regulated in the HM-P2 group throughout gestation. HM-P2 significantly promoted the contents of intestinal caproic acid, bile acids, and tryptophan catabolites such as serotonin. Gut microbes were associated with these bile acids and tryptophans.

Discussion

HM-P2 could modulate the microbial community and microbial metabolites in gestational humanized GF mice. This probiotic strain could be a potential gestational dietary supplement with health benefits.
Positive association between advanced lung cancer inflammation index and gallstones, with greater impact on women: a cross-sectional study of the NHANES database
Authors: Liu Bailiang , Jin Luyuan , Nan Boyuan , Sun Zhongyi , Chen Fengyang , Zhou Yinghui , Sa Qila , Feng Yingnan , Men Ao , Wang Wenxin , Feng Xiaodong , Zhang Wei
Published: December 2024

Background

Previous studies have shown that inflammation is crucial in gallstone formation. The Advanced Lung Cancer Inflammation Index (ALI) is a comprehensive measure that reflects inflammation and nutritional condition. However, there are no studies examining the relationship between ALI and gallstones. This study aimed to analyze this association in US adults.

Methods

This study used a cross-sectional research design with in-depth analyses using data from the National Health and Nutrition Examination Survey (NHANES). The association between gallstones and ALI was systematically assessed by logistic regression analysis, subgroup analysis, basic participant characteristics, and smooth curve fits.

Results

5,646 people participated in the study. ALI was converted into Quartile 1 (−1.47–1.00), Quartile 2 (1.00–1.34), Quartile 3 (1.34–1.69), and Quartile 4 (1.69–4.38). In the fully adjusted model, gallstone prevalence increased by 45% in participants in the highest quartile compared to those in the lowest quartile (OR = 1.45; 95% CI: 1.12–1.87; p = 0.005), and ALI was positively correlated with gallstones (OR = 1.22; 95% CI: 1.03–1.45; p = 0.0232). Smooth curve fits provided evidence in favor of this finding. Significant gender differences were found in the relationship between gallstones and ALI by subgroup analysis (OR = 1.43; 95% CI: 1.16–1.76; p for interaction = 0.0204).

Conclusion

The study concluded that ALI and gallstones had a positive correlation, with ALI having a higher effect on women’s gallstone prevalence.
Diffusion weighted imaging for improving the diagnostic performance of screening breast MRI: impact of apparent diffusion coefficient quantitation methods and cutoffs
Authors: Biswas Debosmita , Hippe Daniel S. , Winter Andrea M. , Li Isabella , Rahbar Habib , Partridge Savannah C.
Published: December 2024

Introduction

Diffusion weighted MRI (DWI) has emerged as a promising adjunct to reduce unnecessary biopsies prompted by breast MRI through use of apparent diffusion coefficient (ADC) measures. The purpose of this study was to investigate the effects of different lesion ADC measurement approaches and ADC cutoffs on the diagnostic performance of breast DWI in a high-risk MRI screening cohort to identify the optimal approach for clinical incorporation.

Methods

Consecutive screening breast MRI examinations (August 2014–Dec 2018) that prompted a biopsy for a suspicious breast lesion (BI-RADS 4 or 5) were retrospectively evaluated. On DWI, ADC (b=0/100/600/800s/mm2) measures were calculated with three different techniques for defining lesion region-of-interest (ROI; single slice(‘2D’), whole volume(‘3D’) and lowest ADC region(‘hotspot’)). An optimal data-derived ADC cutoff for each technique was retrospectively identified to reduce benign biopsies while avoiding any false negatives, inherently producing cutoffs with 100% sensitivity in this particular cohort. Further, diagnostic performance of these measures was validated using two prespecified ADC cutoffs: 1.53x10-3mm2/s from the ECOG-ACRIN A6702 trial and 1.30x10-3mm2/s from the international EUSOBI group. Diagnostic performance was compared between ADC maps generated with 2(0/800s/mm2) and 4(0/100/600/800s/mm2) b-values. Benign biopsy reduction rate was calculated (number of benign lesions with ADC >cutoff)/(total number of benign lesions).

Results

137 suspicious lesions (in 121 women, median age 44 years [range, 20-75yrs]) were detected on contrast-enhanced screening breast MRI and recommended for biopsy. Of those, 30(21.9%) were malignant and 107(78.1%) were benign. Hotspot ADC measures were significantly lower (p<0.001) than ADCs from both 2D and 3D ROI techniques. Applying the optimal data-derived ADC cutoffs resulted in comparable reduction in benign biopsies across ROI techniques (range:16.8% -17.8%). Applying the prespecified A6702 and EUSOBI cutoffs resulted in benign biopsy reduction rates of 11.2-19.6%(with 90.0-100% sensitivity) and 36.4-51.4%(with 70.0-83.3% sensitivity), respectively, across ROI techniques. ADC measures and benign biopsy reduction rates were similar when calculated with only 2 b-values (0,800 s/mm2) versus all 4 b-values.

Discussion

Our findings demonstrate that with appropriate ADC thresholds, comparable reduction in benign biopsies can be achieved using lesion ADC measurements computed from a variety of approaches. Choice of ADC cutoff depends on ROI approach and preferred performance tradeoffs (biopsy reduction vs sensitivity).
Clinicopathologic and ultrasonographic features of combined hepatocellular-cholangiocarcinoma and its correlation with microvascular invasion: a predictive role of contrast-enhanced ultrasound
Authors: Tian HaiYing , Chen Yuling , Zhao LiNa , Liao ChunYan , Li Sha , Zhang Bei
Published: December 2024

Background

This study aims to investigate the clinicopathological and ultrasonography characteristics of combined hepatocellular-cholangiocarcinoma (cHCC-CCA) and its correlation with microvascular invasion (MVI), as well as the predictive value of contrast-enhanced ultrasound (CEUS) imaging.

Methods

A retrospective analysis was conducted on 57 patients diagnosed with cHCC-CCA between November 2017 and May 2023 at Guizhou Provincial People’s Hospital. Among them, 27 patients were MVI-positive and 30 patients were MVI-negative, all of whom underwent preoperative CEUS within 2 weeks. Clinical data, ultrasonographic findings, and CEUS features were compared between the two groups to analyze the influencing factors and predictive value of MVI in cHCC-CCA patients.

Results

Compared to the MVI-negative group, the MVI-positive group showed a higher proportion of tumors with a maximum diameter greater than 5 cm, elevated alpha-fetoprotein (AFP) levels, low echo halo around the tumor, non-smooth tumor contour, peripheral irregular rim-like enhancement and early washout (≤60s) with nodular patterns on CEUS (P<0.05). Multivariate logistic regression analysis revealed that low echo halo, peripheral irregular rim-like enhancement, and early washout were independent risk factors for MVI in cHCC-CCA patients. The receiver operating characteristic (ROC) curve analysis demonstrated an area under the curve (AUC) of 0.8056 for these factors.

Conclusions

Ultrasonographic and CEUS features have a certain correlation with MVI in cHCC-CCA patients. Low echo halo, peripheral irregular rim-like enhancement, and early washout are independent risk factors for MVI in patients with cHCC-CCA. These features have a predictive value in determining the presence of MVI in patients with cHCC-CCA.
The role of MEK inhibition in pediatric low-grade gliomas
Authors: Sheikh Shehryar R. , Klesse Laura J. , Mangum Ross , Bui Ashley , Siegel Benjamin I. , Abdelbaki Mohamed S. , Patel Neha J.
Published: December 2024

Pediatric low-grade gliomas (pLGGs) are the most common brain tumors in children. Many patients with unresectable tumors experience recurrence or long-term sequelae from standard chemotherapeutics. This mini-review explores the emerging role of MEK inhibitors in the management of pLGGs, highlighting their potential to transform current treatment paradigms. We review the molecular basis for therapeutic MEK inhibition in the context of pLGG, provide an evidence base for the use of the major MEK inhibitors currently available in the market for pLGG, and review the challenges in the use of MEKi inhibitors in this population.
Management of choroidal/ciliary body metastasis in the era of targeted cancer therapy
Authors: Evbuomwan Moses O. , Bhuyan Rupak , Uzomah Uwajachukwumma A. , Jamshidi Farzad , Anderson Carryn , Boldt H. Culver , Binkley Elaine
Published: December 2024

Introduction

Choroidal metastases from systemic malignancies are the most common intraocular malignancies in adults. External beam radiation (EBR) has historically been first-line therapy for metastatic tumors to the choroid. However, good responses have been described with newer targeted biologics. The optimal management strategy for patients with choroidal metastatic tumors in the era of targeted cancer therapy is not known. We aim to describe management of these tumors in a “real-world” setting using both radiation and systemic therapy.

Methods

We conducted a retrospective review of patients with choroidal/ciliary body metastases managed by the ocular oncology service at our institution over a five-year period. Demographic data, tumor type, treatment, visual outcomes, and mortality data were recorded.

Results

26 patients (33 eyes) with choroidal/ciliary body metastasis were identified. Primary malignancies included lung (8) breast (8), renal (3), esophageal (3), carcinoid (2), squamous cell carcinoma of the tonsil (1), and testicular cancer (1). Average time from diagnosis of ocular metastasis to death was 8 months (1-34). 20 eyes were treated with EBR and 13 eyes were treated with other modalities. Final logMAR visual acuity for eyes treated with radiation was 0.11 (0-3). Final visual acuity for eyes treated with other modalities was 0.18 (0-.70), with local tumor control in 20/23 eyes that had follow up after treatment. The difference between final visual acuity in these groups was not visually significant p=0.48.

Conclusion

Patients with choroidal/ciliary body metastasis treated with either EBR or systemic therapy can have good visual outcomes. More work needs to be conducted to determine the optimal first-line treatment of ocular metastasis for specific tumor subtypes.
Effect of icariin on ovarian cancer: a combined network pharmacology and meta-analysis of in vitro studies approach
Authors: Cao Shang-Mei , Chen Bo-Lin , Zou Zhen-Zhen , Yang Shao-Zhe , Fu Xiu-Hong
Published: December 2024

Introduction

An abundance of experimental evidence indicates that icariin (ICA) could potentially exert an anti-tumor effect on ovarian cancer (OC). Nevertheless, the reliability of this evidence remains ambiguous. This study aimed to explore the impact of ICA on OC and the underlying mechanisms.

Methods

Bioinformatics analysis was employed to pinpoint ICA-targeted genes and signaling pathways implicated in OC, utilizing network pharmacology. Subsequently, PubMed, EMBASE, and Web of Science databases were systematically searched from 2001 through June 2023 for in vitro trials evaluating the anti-tumor efficacy of conventional ICA versus placebo in OC. The pathways and genes identified in the literature were recorded, and the therapeutic targets were statistically analyzed and compared with the predicted targets from network pharmacology to confirm the precision of the targets.

Results and Discussion

Fourteen target genes were validated with success. The pathways corresponding to the remaining genes—excluding these 14—were analyzed and found to be primarily associated with cell apoptosis, anti-tumor, and other related pathways. Out of the 76 studies retrieved, eight fulfilled the inclusion criteria. The subsequent meta-analysis suggested that ICA treatment was significantly correlated with reduced cell growth and induced apoptosis. This study demonstrated a certain efficacy of ICA compared to placebo in enhancing anti-tumor outcomes, characterized by increased abilities in reducing cell growth and inducing apoptosis. The pathways involved in the therapeutic effect may be linked to cell apoptosis and anti-tumor mechanisms.
The novel pleuromutilin derivative 22–((4-((4-nitrophenyl)acetamido)phenyl)thio)deoxy pleuromutilin possesses robust anti-mycoplasma activity both in vitro and in vivo
Authors: Xia Xirui , Ji Xuan , Li Yaxi , Wang Yubo , Zhao Yue , Wang Wenxiang , Ding Huanzhong
Published: December 2024

Objective

Mycoplasmas are structurally simple pathogenic microorganisms that can cause a wide range of diseases in humans and animals and conventional antibiotic therapies of fluoroquinolones and tetracyclines are toxic to young children and young animals and macrolide resistance is increasing. In this context, new anti-mycoplasma antimicrobial agents need to be developed. 22–((4-((4-nitrophenyl)acetamido)phenyl)thio)deoxypleuromutilin (compound 16C) is a novel acetamine phenyl pleuromutilin derivative. This study aimed to evaluate its acute toxicity in mice and generate pharmacokinetic and anti-mycoplasma profiles.

Methods

The safety of compound 16C was preliminarily evaluated by oral and intramuscular acute toxicity tests and single intravenous and intramuscular pharmacokinetic experiments were performed to obtain its pharmacokinetic profile. The minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and time-killing curves reflected the in vitro effects of the compounds against Mycoplasma pneumoniae. Five groups consisted of three treatments for compound 16C (20, 40, and 80 mg/kg), and two treatments for tiamulin (oral and intramuscular 40 mg/kg) were continued for 4 d. Bronchoalveolar lavage fluid (BALF) and lung tissues were collected at the end of treatment (96 h) and 4 days later (192 h) to assess the in vivo anti-mycoplasma and anti-pneumonia effects. ELISA assays were performed to detect IFN-γ, TNF-α, and IL-8 (CXCL1) in BALF. Lung tissues were fixed with 4% paraformaldehyde and sectioned for histopathological assessment.

Results

The results show that compound 16C has low toxicity (LD50 > 5,000 mg/kg). Its pharmacokinetic profile is characterized by a short time to maximum concentration (Tmax = 0.24 h), high bioavailability (F = 71.29%), and short elimination half-life (T1/2kel) (intramuscular and intravenous administration was 2.20 and 1.89 h, respectively). Treatment with compound 16C and intramuscular tiamulin reduced the mycoplasma load in mice. Intramuscular compound 16C and tiamulin also inhibited the release of IFN-γ, TNF-α, and CXCL1, decreasing the accumulation of inflammatory cells in the lungs, thereby mitigating lung damage.

Conclusion

This study proved that compound 16C has a strong antimicrobial effect against M. pneumoniae, can be rapidly absorbed and has therapeutic efficacy that provides a basis for developing new anti-mycoplasma drugs.
Tenecteplase: biochemical and clot lysis activity comparisons
Authors: Bechmann Jan , Schmid Ira , Brand Simone , Miller Felix , Zhang Chengzhi
Published: December 2024

Introduction

In the last decades, the recombinant tissue plasminogen activator alteplase has been the standard fibrinolytic treatment of acute myocardial infarction, pulmonary embolism, and acute ischemic stroke. An optimized version of alteplase, tenecteplase, has been developed by exchanging six amino acids to increase half-life, achieve higher fibrin selectivity and increase resistance to plasminogen activator inhibitor-1. Meanwhile, several products containing tenecteplase exist. The aim of this study was to compare the fibrinolytic activity and overall product quality of the 25 mg/vial presentation of tenecteplase originator Metalyse® (Boehringer Ingelheim Pharma GmbH and Co., KG, Ingelheim, Germany) to the 16 mg/vial formulation of the tenecteplase copy Mingfule® (CSPC Recomgen Pharmaceutical, Guangzhou, Co., Ltd.).

Methods

We have systematically analyzed and evaluated the biochemical and fibrinolytic differences between Metalyse® and Mingfule® using a wide range of routine quality testing assays, supplemented by mass spectrometry analysis and surface plasmon resonance assays. Additional host cell protein quantification and clot lysis testing following plasmin incubation over time were performed.

Results

Several key differences in biochemical composition and clot lysis activity were observed between the two tenecteplase variants. Versus Metalyse®, Mingfule® exhibited lower clot lysis activity and contained less of the two-chain form of tenecteplase. In addition, there were differences in sialic acid content, galactosylation, and fucosylation patterns, with Mingfule® exhibiting more bi- and less tri- and tetra-antennary glycosylation, leading to a different charge and size heterogeneity profile. Furthermore, Mingfule® displayed highly dissimilar binding to the three clearance receptors (LRP-1, ASGR, and mannose receptor) compared with Metalyse®. Purity analysis showed that Mingfule® contained a lower monomer content and, in contrast to Metalyse®, substantial amounts of host cell protein.

Discussion

Taken together, these data demonstrate that the tenecteplase copy Mingfule® has several meaningful fibrinolytic and biochemical differences compared with Metalyse®. This raises the question of whether data from clinical studies with one of the products can be generalized for all tenecteplase variants.
SARS-CoV-2 detection by surface plasmon resonance biosensors based on graphene-multilayer structures
Authors: Tene Talia , Guevara Marco , Romero Paul , Guapi Alberto , Gahramanli Lala , Vacacela Gomez Cristian
Published: December 2024

The COVID-19 pandemic has created a demanding need for fast, sensitive, and reliable diagnostic methods to identify viral infections like SARS-CoV-2. In response, surface plasmon resonance (SPR) biosensors have emerged as effective tools for detecting biomolecules. This theoretical study focuses on designing and refining multilayer SPR biosensor configuration to ensure high sensitivity and stability. The optimized configuration consists of a thin silver layer, a silicon nitride layer, a single graphene layer, and a ssDNA bioreceptor layer, each tailored to improve the effectiveness of the proposed biosensor. The capability of the biosensor to detect SARS-CoV-2 is assessed by analyzing its SPR response, specifically examining variations in resonance angle, attenuation, full width at half maximum, and sensitivity across a range of viral concentrations. Additionally, this study evaluated performance metrics such as refractive index sensitivity, detection accuracy, and quality factor to determine the effectiveness of the biosensor against SARS-CoV-2. Then, this work establishes a basis for further development of SPR biosensors aimed at various viral and biomolecular targets, supporting advances in biosensing technology and the creation of effective diagnostic tools to address current and future health challenges.
Nuclear structure and direct reaction studies in particle-γ coincidence experiments at the FSU John D. Fox superconducting linear accelerator laboratory
Authors: Spieker Mark-Christoph , Almaraz-Calderon Sergio
Published: December 2024

Since its foundation in the 1960s, the John D. Fox Superconducting Linear Accelerator Laboratory at Florida State University (FSU) pursued research at the forefront of nuclear science. In this contribution, we present recent highlights from nuclear structure and reaction studies conducted at the John D. Fox Superconducting Linear Accelerator Laboratory, also featuring the general experimental capabilities at the laboratory for particle-γ coincidence experiments. Specifically, we focus on light-ion induced reactions measured with the Super-Enge Split-Pole Spectrograph (SE-SPS) and the CATRiNA neutron detectors, respectively. Some results obtained with the CeBrA demonstrator for particle-γ coincidence experiments at the SE-SPS are presented. A highlight from the first experimental campaigns with the combined CLARION2-TRINITY setup, showing that weak reaction channels can be selected, is discussed as well.
Multi-Conv attention network for skin lesion image segmentation
Authors: Li Zexin , Wang Hanchen , Chen Haoyu , Lin Chenxin , Yan Aochen
Published: December 2024

To address the trade-off between segmentation performance and model lightweighting in computer-aided skin lesion segmentation, this paper proposes a lightweight network architecture, Multi-Conv Attention Network (MCAN). The network consists of two key modules: ISDConv (Inception-Split Depth Convolution) and AEAM (Adaptive Enhanced Attention Module). ISDConv reduces computational complexity by decomposing large kernel depthwise convolutions into smaller kernel convolutions and unit mappings. The AEAM module leverages dimensional decoupling, lightweight multi-semantic guidance, and semantic discrepancy alleviation to facilitate the synergy between channel attention and spatial attention, further exploiting redundancy in the spatial and channel feature maps. With these improvements, the proposed method achieves a balance between segmentation performance and computational efficiency. Experimental results demonstrate that MCAN achieves state-of-the-art performance on mainstream skin lesion segmentation datasets, validating its effectiveness.
Multimodal MRI radiomics-based stacking ensemble learning model with automatic segmentation for prognostic prediction of HIFU ablation of uterine fibroids: a multicenter study
Authors: Wen Bing , Li Chengwei , Cai Qiuyi , Shen Dan , Bu Xinyi , Zhou Fuqiang
Published: December 2024

Objectives

To evaluate the effectiveness of an MRI radiomics stacking ensemble learning model, which combines T2-weighted imaging (T2WI) and contrast-enhanced T1-weighted imaging (CE-T1WI) with deep learning-based automatic segmentation, for preoperative prediction of the prognosis of high-intensity focused ultrasound (HIFU) ablation of uterine fibroids.

Methods

This retrospective study collected data from 360 patients with uterine fibroids who underwent HIFU treatment. The dataset was sourced from Center A (training set: N = 240; internal test set: N = 60) and Center B (external test set: N = 60). Patients were categorized into favorable and unfavorable prognosis groups based on the post-treatment non-perfused volume ratio. Automated segmentation of uterine fibroids was performed using a V-net deep learning models. Radiomics features were extracted from T2WI and CE-T1WI, followed by data preprocessing including normalization and scaling. Feature selection was performed using t-test, Pearson correlation, and LASSO to identify the most predictive features for preoperative prognosis Support Vector Machine (SVM), Random Forest (RF), Light Gradient Boosting Machine (LightGBM), and Multilayer Perceptron (MLP) were employed as base learners to construct base predictive models. These models were integrated into a stacking ensemble model, with Logistic Regression serving as the meta-learner to combine the outputs of the base models. The performance of the models was assessed using the area under the receiver operating characteristic curve (AUC).

Results

Among the base models developed using T2WI and CE-T1WI features, the MLP model exhibited superior performance, achieving an AUC of 0.858 (95% CI: 0.756–0.959) in the internal test set and 0.828 (95% CI: 0.726–0.930) in the external test set. It was followed by the SVM, LightGBM, and RF, which obtained AUC values of 0.841 (95% CI: 0.737–0.946), 0.823 (95% CI: 0.711–0.934), and 0.750 (95% CI: 0.619–0.881), respectively. The stacking ensemble learning model, which integrated these five algorithms, demonstrated a notable enhancement in performance, with an AUC of 0.897 (95% CI: 0.818–0.977) in the internal test set and 0.854 (95% CI: 0.759–0.948) in the external test set.

Conclusion

The DL based automatic segmentation MRI radiomics stacking ensemble learning model demonstrated high accuracy in predicting the prognosis of HIFU ablation of uterine fibroids.
Relay intercropped soybean promotes nodules development and nitrogen fixation by root exudates deposition
Authors: Lin Ping , Wang Jin , Chen Ping , Fu Zhidan , Luo Kai , Li Yiling , Pu Tian , Wang Xiaochun , Yong Taiwen , Yang Wenyu
Published: December 2024

Background

Legumes, in the initial event of symbiosis, secrete flavonoids into the rhizosphere to attract rhizobia. This study was conducted to investigate the relationship between crop root exudates and soybean nodule development under intercropping patterns.

Method

A two years field experiments was carried out and combined with pot experiments to quantify the effects of planting mode, i.e., relay intercropping and monocropping, and genotypes, i.e., supernodulating NTS1007(NTS), Nandou-12(ND) and Guixia-3(GX) on root exudates, rhizobium community structure, nodule development and nitrogen fixation ability.

Result

The result demonstrated that, maize–soybean relay strip intercropping not only promoted daidzein and genistein exudates of soybean root to soil but also reshaped the community structure and diversity of nodule endophytic rhizobia. Compared with monocropping, the nodule number significantly decreased in relay strip intercropping soybean, and NTS achieved 97% at soybean five trifoliolate stage. At soybean full bloom stage, despite the nodulation capacity of relay strip intercropping soybean was unrestored, the nodule number, nodule dry weight, nodule diameter and root dry weight were the highest in ND under relay strip intercropping. Compared with monocropping, the nodule average diameters of ND and GX in relay strip intercropping significantly increased 26.30% and 21.11%, respectively, the single nodule nitrogenase activity and nifH gene was increased up to the higher level of 3.16-fold and 1.96-fold, 70.8% and 107.6%, respectively. Combined with pot experiments, the nodule number of ND and NTS in maize root maize root exudates (RE) treatment increased with growth period, the GX reached its maximum at full bloom stage. And the nodule diameter of ND under RE treatment showed the best response. At R2 stage, compared with distilled water (DW) treatment, the nodule average diameter of ND and GX in RE treatment was significantly higher, and the GmEXPB2 gene was significantly up-regulated 3.99-fold and 1.02-fold, respectively.

Conclusion

In brief, the maize–soybean relay strip intercropping enhanced the soybean root exudates nodulation signaling molecules, meanwhile, maize root exudates caused increased nodule diameter, and enhanced nodule nitrogen fixation, but had little effect on supernodulation varieties.
Rapid and accurate detection of Fusarium oxysporum f. sp. Lycopersici using one-pot, one-step LAMP-CRISPR/Cas12b method
Authors: Dai Shijie , Wu Yangsheng , Zhu Na , Zhao Yujin , Mao Mingjiang , Li Zheming , Zhu Bo , Zhao Weichun , Yuan Xiaofeng
Published: December 2024

Introduction

Fusarium oxysporum f. sp. Lycopersici (Fol) is one of the most devastating plant pathogenic fungi, the causal agent of root rot for Atractylides macrocephala Koidz (AMK). An accurate rapid and convenient diagnosis for FoL detection is essential for determining management practices and preventing future losses for AMK.

Methods

Here, we developed a novel method for Fol detection by integrating loop-mediated isothermal amplification (LAMP) assay and CRISPR/Cas12b detection in one-pot, and the whole reaction can simultaneously amplify and detect the target gene of Fol in one-step.

Results

The total time of the present method is limited to 45 min and isothermally performed at 60°C. The limit of detection of this assay is 88.9 copies per reaction. The specificity of the LAMP-CRISPR/Cas12b method was 100% without any cross-reaction of other pathogens. A total of 24 nucleic acid samples were used to evaluate the performance of the LAMP-CRISPR/Cas12b method, including 12 with-Fol and 12 without-Fol. Compared with the gold standard results from real-time PCR, the present method provides a sensitivity of 100% (12/12), specificity of 100% (12/12), and consistency of 100% (24/24).

Discussion

Together, our preliminary results illustrated that the LAMP-CRISPR/Cas12b method is a rapid simple, and reliable tool for Fol diagnosis and could be applied in point-of-need phytopathogen detection.