bluuebunny/crossref_metadata_2025 huggingface dataset:
Live birth rate per fresh embryo transfer and cumulative live birth rate in patients with PCOS under the POSEIDON classification: a retrospective study
Authors: Jiang Linlin , Sun Yiting , Pan Ping , Li Lin , Yang Dongzi , Huang Jia , Li Yu
Published: May 2024

Background

Ovarian stimulation (OS) for in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) in women with PCOS often results in multiple follicular development, yet some individuals experience poor or suboptimal responses. Limited data exist regarding the impact of poor/suboptimal ovarian response on pregnancy outcomes in women with PCOS.

Objectives

The aim of this study was to evaluate whether the live birth rate (LBR) per fresh embryo transfer and cumulative live birth rate (CLBR) per aspiration cycle differ in women with PCOS defined by the Patient-Oriented Strategy Encompassing IndividualizeD Oocyte Number (POSEIDON) criteria.

Methods

A retrospective study involving 2,377 women with PCOS who underwent their first IVF/ICSI cycle at Sun Yat-sen Memorial Hospital from January 2011 to December 2020 was used. Patients were categorized into four groups based on age, antral follicle count, and the number of oocytes retrieved, according to the POSEIDON criteria. The LBR and CLBR were compared among these groups. Logistic regression analysis was performed to assess whether the POSEIDON criteria served as independent risk factors and identify factors associated with POSEIDON.

Results

For patients <35 years old, there was no significant difference in the clinical pregnancy rate between POSEIDON and non-POSEIDON patients, whereas POSEIDON patients exhibited lower rates of implantation and live birth. POSEIDON Group 1a displayed lower rates of implantation, clinical pregnancy, and live birth. However, no significant differences were observed in the rates of clinical pregnancy and live birth between POSEIDON Group 1b and non-POSEIDON groups. For patients ≥35 years old, there were no significant differences in the rates of implantation, clinical pregnancy, and live birth between POSEIDON and non-POSEIDON patients. CLBRs were significantly lower in POSEIDON Groups 1 and 2, compared with the non-POSEIDON groups. The levels of body mass index (BMI), follicle-stimulating hormone (FSH), and antral follicle count (AFC) were associated with POSEIDON hypo-response. POSEIDON was found to be associated with lower CLBR, but not LBR per fresh embryo transfer.

Conclusions

In patients with PCOS, an unexpected suboptimal response can achieve a fair LBR per fresh embryo transfer. However, CLBR per aspirated cycle in POSEIDON patients was lower than that of normal responders. BMI, basal FSH level, and AFC were independent factors associated with POSEIDON. Our study provides data for decision-making in women with PCOS after an unexpected poor/suboptimal response to OS.
The causal relationship between 5 serum lipid parameters and diabetic nephropathy: a Mendelian randomization study
Authors: Liu Hongzhou , Yao Xinxia , Wang Linlin , Liu Jia , Li Xiaojing , Fu Xiaomin , Liu Jing , Dong Song , Wang Yuhan
Published: May 2024

Background

Serum lipids were found to be correlated with chronic kidney disease and cardiovascular disease. Here, we aimed to research the potential causal associations between five serum lipid parameters and the risk of diabetic nephropathy using several Mendelian Randomization methods.

Methods

Genetic data was obtained from the UK Biobank datasets. Causal effects were estimated using multiple MR methods. Heterogeneity and pleiotropy tests were performed.

Results

MR analysis revealed that HDL-C and TG exhibited causal associations with diabetic nephropathy (P<0.05). Similar trends were not observed for other lipid parameters.

Conclusions

Our research has suggested links between HDL-C, TG and diabetic nephropathy. The findings could contribute to further elucidation of the disease etiology.

Strengths and limitations of this study

This article only uses Mendel randomization method to analyze the relationship between blood lipids and diabetes nephropathy, which is more convincing when combined with population data.
Research on the risk assessment of the power grid enterprises’ agency power purchase business in China: A hybrid multi-attribute decision-making framework based on FUCOM-F and GRA-MARCOS
Authors: Gan Yue , Zheng Chaofeng , Chu Baoju , Li Jianfang , Zhang Yuanyuan , Jia Yixin
Published: May 2024

To steadily promote the reform of sales electricity prices, China has innovatively proposed to carry out grid enterprises’ agency power purchase business (GEAPPB) as a transitional scheme for industrial and commercial users to enter the power market in the future. However, because the GEAPPB covers a wide range of users and involves complex business processes, the risks throughout the process of the GEAPPB will affect the organization and operation of the business. This paper proposes a GEAPPB risk assessment technique. First, a risk evaluation index system containing 10 indicators is designed based on the characteristics and development process of GEAPPB. Second, a risk assessment model based on the fuzzy full consistency method (FUCOM-F) and gray relational analysis (GRA)-improved MARCOS is constructed. Finally, seven grid enterprises in China are taken as examples to verify the validity and scientificity of the model. The results show that improving the accuracy of power forecasting, optimizing the agency power purchase strategy, and strengthening demand response management are the key schemes to reduce the risk of GEAPPB. Compared with the other three evaluation models, the proposed model has good applicability and effectiveness for the risk evaluation of GEAPPB.
The impact of information provision on public willingness to use recycled water for flushing from the perspective of risk perception
Authors: Ding Yizhe , Liu Xiaojun
Published: May 2024

To solve the current urban water shortage, increasing the willingness of urban residents to use recycled water for flushing is one proposed approach. This study developed a risk perception measurement model of recycled water for toilet flushing to explore which risk triggered people’s risk perception of recycled water, and then analyzed the interaction among information provision, trust, risk perception, and willingness to use recycled water. The main results were as follows. First, the risk perception of recycled water for flushing mainly come from four types of risks, which were performance risk, health risk, service risk and financial risk in order of importance. Second, reducing the perceived risk can improve public willingness to use recycled water for flushing, and greater trust in the water authorities and recycled water enterprises reduces the public’s perception of the risk of recycled water. A higher level of initial trust is related to higher willingness to use recycled water. Third, information provision can enhance the risk perception of recycled water and enhance trust in the water authorities and recycled water enterprises, but information provision does not directly affect the willingness to use recycled water. This indicates that reducing performance risk and health risk of recycled water, will be the key to controlling the overall risk perception of recycled water and promoting willingness to use. Effective risk communication strategies combine information provision and trust in information providers, which together affect risk perception and thus the willingness to use recycled water.
Case report: Pilomatrix carcinoma with PDL1 expression and CDKN2A aberrant
Authors: Abula Ayinuer , Ma Sheng-Qiang , Wang Sisi , Peng Wei , Pei Xiaming , Hu Zhe-Yu
Published: May 2024

Case report

A 55-year-old male patient developed a mass in the left inguinal area with left lower limb swelling and first visited a local hospital 3 months earlier because of unrelieved pain. An MRI scan suggested left suprapubic branch and left acetabular bone destruction, abnormal soft tissue signals within the iliopsoas muscle of the anterior edge of the left iliac bone, and enlarged lymph nodes in the left iliac fossa and left inguinal region. The patient subsequently underwent left pelvic lesion open biopsy and inguinal lymph node resection biopsy. According to pathological reports, the left inguinal mass was considered to be a malignant tumor of cutaneous accessory origin (pilomatrix carcinoma) with extensive vitreous changes. The suprapupubis branch mass was considered to be a bone metastatic pilomatrix carcinoma. Immunohistochemistry (IHC) revealed a PDL1 combined positive score (CPS) of 8. DNA next-generation sequencing (NGS) showed CDKN2A L65Rfs*53 mutation. The patient received three cycles of gemcitabine and nedaplatin. However, the lesion progressed.

Conclusion

Chemotherapy is not effective for treating pilomatrix carcinoma. PDL1 antibodies and CDK4/6 inhibitors might be treatment options for pilomatrix carcinoma.
Exploring risk factors for autoimmune diseases complicated by non-hodgkin lymphoma through regulatory T cell immune-related traits: a Mendelian randomization study
Authors: Liu Qi , Zhou Xintong , Liu Kunjing , Wang Yimin , Liu Cun , Gao Chundi , Cai Qingqing , Sun Changgang
Published: May 2024

Background

The effect of immune cells on autoimmune diseases (ADs) complicated by non-Hodgkin lymphoma (NHL) has been widely recognized, but a causal relationship between regulatory T cell (Treg) immune traits and ADs complicated by NHL remains debated.

Methods

Aggregate data for 84 Treg-related immune traits were downloaded from the Genome-Wide Association Study (GWAS) catalog, and GWAS data for diffuse large B-cell lymphoma (DLBCL; n=315243), follicular lymphoma (FL; n=325831), sjögren’s syndrome (SS; n=402090), rheumatoid arthritis (RA; n=276465), dermatopolymyositis (DM; n=311640), psoriasis (n=407876), atopic dermatitis (AD; n=382254), ulcerative colitis (UC; n=411317), crohn’s disease(CD; n=411973) and systemic lupus erythematosus (SLE; n=307587) were downloaded from the FinnGen database. The inverse variance weighting (IVW) method was mainly used to infer any causal association between Treg-related immune traits and DLBCL, FL, SS, DM, RA, Psoriasis, AD, UC, CD and SLE, supplemented by MR-Egger, weighted median, simple mode, and weighted mode. Moreover, we performed sensitivity analyses to assess the validity of the causal relationships.

Results

There was a potential genetic predisposition association identified between CD39+ CD8br AC, CD39+ CD8br % T cell, and the risk of DLBCL (OR=1.51, p<0.001; OR=1.25, p=0.001) (adjusted FDR<0.1). Genetic prediction revealed potential associations between CD25++ CD8br AC, CD28- CD25++ CD8br % T cell, CD39+ CD8br % CD8br, and the risk of FL (OR=1.13, p=0.022; OR=1.28, p=0.042; OR=0.90, p=0.016) (adjusted FDR>0.1). Furthermore, SLE and CD exhibited a genetically predicted potential association with the CD39+ CD8+ Tregs subset. SS and DM were possibly associated with an increase in the quantity of the CD4+ Tregs subset; RA may have reduced the quantity of the CD39+ CD8+ Tregs subset, although no causal relationship was identified. Sensitivity analyses supported the robustness of our findings.

Conclusions

There existed a genetically predicted potential association between the CD39+ CD8+ Tregs subset and the risk of DLBCL, while SLE and CD were genetically predicted to be potentially associated with the CD39+ CD8+ Tregs subset. The CD39+ CD8+ Tregs subset potentially aided in the clinical diagnosis and treatment of SLE or CD complicated by DLBCL.
Neuronal nicotinic acetylcholine receptor antibodies in autoimmune central nervous system disorders
Authors: Pechlivanidou Maria , Vakrakou Aigli G. , Karagiorgou Katerina , Tüzün Erdem , Karachaliou Eleni , Chroni Elisabeth , Afrantou Theodora , Grigoriadis Nikolaos , Argyropoulou Christina , Paschalidis Nikolaos , Şanlı Elif , Tsantila Aikaterini , Dandoulaki Maria , Ninou Elpinickie I. , Zisimopoulou Paraskevi , Mantegazza Renato , Andreetta Francesca , Dudeck Leon , Steiner Johann , Lindstrom Jon Martin , Tzanetakos Dimitrios , Voumvourakis Konstantinos , Giannopoulos Sotirios , Tsivgoulis Georgios , Tzartos Socrates J. , Tzartos John
Published: May 2024

Background

Neuronal nicotinic acetylcholine receptors (nAChRs) are abundant in the central nervous system (CNS), playing critical roles in brain function. Antigenicity of nAChRs has been well demonstrated with antibodies to ganglionic AChR subtypes (i.e., subunit α3 of α3β4-nAChR) and muscle AChR autoantibodies, thus making nAChRs candidate autoantigens in autoimmune CNS disorders. Antibodies to several membrane receptors, like NMDAR, have been identified in autoimmune encephalitis syndromes (AES), but many AES patients have yet to be unidentified for autoantibodies. This study aimed to develop of a cell-based assay (CBA) that selectively detects potentially pathogenic antibodies to subunits of the major nAChR subtypes (α4β2- and α7-nAChRs) and its use for the identification of such antibodies in “orphan” AES cases.

Methods

The study involved screening of sera derived from 1752 patients from Greece, Turkey and Italy, who requested testing for AES-associated antibodies, and from 1203 “control” patients with other neuropsychiatric diseases, from the same countries or from Germany. A sensitive live-CBA with α4β2-or α7-nAChR–transfected cells was developed to detect antibodies against extracellular domains of nAChR major subunits. Flow cytometry (FACS) was performed to confirm the CBA findings and indirect immunohistochemistry (IHC) to investigate serum autoantibodies’ binding to rat brain tissue.

Results

Three patients were found to be positive for serum antibodies against nAChR α4 subunit by CBA and the presence of the specific antibodies was quantitatively confirmed by FACS. We detected specific binding of patient‐derived serum anti‐nAChR α4 subunit antibodies to rat cerebellum and hippocampus tissue. No serum antibodies bound to the α7-nAChR-transfected or control-transfected cells, and no control serum antibodies bound to the transfected cells. All patients positive for serum anti‐nAChRs α4 subunit antibodies were negative for other AES-associated antibodies. All three of the anti‐nAChR α4 subunit serum antibody-positive patients fall into the AES spectrum, with one having Rasmussen encephalitis, another autoimmune meningoencephalomyelitis and another being diagnosed with possible autoimmune encephalitis.

Conclusion

This study lends credence to the hypothesis that the major nAChR subunits are autoimmune targets in some cases of AES and establishes a sensitive live-CBA for the identification of such patients.
Interpretable deep learning reveals the role of an E-box motif in suppressing somatic hypermutation of AGCT motifs within human immunoglobulin variable regions
Authors: Tambe Abhik , MacCarthy Thomas , Pavri Rushad
Published: May 2024

Introduction

Somatic hypermutation (SHM) of immunoglobulin variable (V) regions by activation induced deaminase (AID) is essential for robust, long-term humoral immunity against pathogen and vaccine antigens. AID mutates cytosines preferentially within WRCH motifs (where W=A or T, R=A or G and H=A, C or T). However, it has been consistently observed that the mutability of WRCH motifs varies substantially, with large variations in mutation frequency even between multiple occurrences of the same motif within a single V region. This has led to the notion that the immediate sequence context of WRCH motifs contributes to mutability. Recent studies have highlighted the potential role of local DNA sequence features in promoting mutagenesis of AGCT, a commonly mutated WRCH motif. Intriguingly, AGCT motifs closer to 5’ ends of V regions, within the framework 1 (FW1) sub-region1, mutate less frequently, suggesting an SHM-suppressing sequence context.

Methods

Here, we systematically examined the basis of AGCT positional biases in human SHM datasets with DeepSHM, a machine-learning model designed to predict SHM patterns. This was combined with integrated gradients, an interpretability method, to interrogate the basis of DeepSHM predictions.

Results

DeepSHM predicted the observed positional differences in mutation frequencies at AGCT motifs with high accuracy. For the conserved, lowly mutating AGCT motifs in FW1, integrated gradients predicted a large negative contribution of 5’C and 3’G flanking residues, suggesting that a CAGCTG context in this location was suppressive for SHM. CAGCTG is the recognition motif for E-box transcription factors, including E2A, which has been implicated in SHM. Indeed, we found a strong, inverse relationship between E-box motif fidelity and mutation frequency. Moreover, E2A was found to associate with the V region locale in two human B cell lines. Finally, analysis of human SHM datasets revealed that naturally occurring mutations in the 3’G flanking residues, which effectively ablate the E-box motif, were associated with a significantly increased rate of AGCT mutation.

Discussion

Our results suggest an antagonistic relationship between mutation frequency and the binding of E-box factors like E2A at specific AGCT motif contexts and, therefore, highlight a new, suppressive mechanism regulating local SHM patterns in human V regions.
ROTracker: a novel MMW radar-based object tracking method for unmanned surface vehicle in offshore environments
Authors: Xu Hu , Zhang Xiaomin , He Ju , Pang Changsong , Yu Yang
Published: May 2024

Unmanned surface vehicles (USVs) offer significant value through their capability to undertake hazardous and time-consuming missions across water surfaces. Recently, as the application of USVs has been extended to nearshore waterways, object tracking is vital to the safe navigation of USVs in offshore scenes. However, existing tracking systems for USVs are mainly based on cameras or LiDAR sensors, which suffer from drawbacks such as lack of depth perception or high deployment costs. In contrast, millimeter-wave (MMW) radar offers advantages in terms of low cost and robustness in all weather and lighting conditions. In this work, to construct a robust and low-cost tracking system for USVs in complex offshore scenes, we propose a novel MMW radar-based object tracking method (ROTracker). The proposed ROTracker combines the physical properties of MMW radar with traditional tracking systems. Specifically, we introduce the radar Doppler velocity and a designed motion discriminator to improve the robustness of the tracking system toward low-speed targets. Moreover, we conducted real-world experiments to validate the efficacy of the proposed ROTracker. Compared to other baseline methods, ROTracker achieves excellent multiple object tracking accuracy in terms of 91.9% in our collected dataset. The experimental results demonstrated that the proposed ROTracker has significant application potential in both accuracy and efficiency for USVs, addressing the challenges posed by complex nearshore environments.
Insights into disability and psycho-social care of patients with inflammatory bowel disease
Authors: Nardone Olga Maria , Calabrese Giulio , La Mantia Alessia , Caso Rossella , Testa Anna , Castiglione Fabiana
Published: May 2024

In recent years, the concept of disability has increasingly garnered attention as a crucial long-term target of inflammatory bowel disease (IBD) management. The treatment paradigm has changed dramatically from full control of the disease (clinical and endoscopic remission) toward physical and emotional well-being with the goal of preventing disability and normalizing quality of life. However, in certain cases, despite achieving good disease control, patients may still experience symptoms associated with disability, and reduced emotional wellness. These symptoms can significantly impact various biopsychosocial factors, including interpersonal relationships, educational or work-related activities, body image, and sexual functioning. Nevertheless, they often remain overlooked in the context of IBD care. In this narrative review, we aim to shed light on the burden of certain disability-related symptoms such as bowel urgency, sexual dysfunction, impaired fertility and fatigue, emphasizing the importance of acknowledging and validating them in a clinical setting. There is a demanding need for comprehensive care for IBD patients, with IBD clinicians being mindful of the psychosocial challenges faced by their patients. Providing timely and appropriate management of these challenges alongside IBD treatment is key to achieving holistic remission and enhancing the overall quality of life while reducing disability.
Identification of Mycoplasma pneumoniae proteins interacting with NOD2 and their role in macrophage inflammatory response
Authors: Wang Yongyu , Ma Chunji , Hao Xiujing , Wang Weili , Luo Haixia , Li Min
Published: May 2024

Mycoplasma pneumoniae (M. pneumoniae, Mp) is a cell wall-deficient microorganism known to cause chronic respiratory infections in both children and adults. Nucleotide-binding oligomerization domain-containing protein 2 (NOD2) is an intracellular pattern recognition receptor primarily responsible for identifying muramyl dipeptide (MDP) found in bacterial cell walls. Previous experiments have demonstrated that Mycoplasma ovipneumoniae induces macrophage autophagy through NOD2. In this study, we conducted RNA-seq analysis on macrophages infected with M. pneumoniae and observed an up-regulation in the expression of genes associated with the NOD2 signaling pathway. Mechanistic investigations further revealed the involvement of the NOD2 signaling pathway in the inflammatory response of macrophages activated by M. pneumoniae. We utilized GST pull-down technology in conjunction with liquid chromatography–tandem mass spectrometry (LC–MS/MS) to pinpoint the M. pneumoniae proteins that interact with NOD2. Additionally, co-immunoprecipitation (Co-IP) and immunofluorescence co-localization techniques were used to confirm the interaction between DUF16 protein and NOD2. We found that DUF16 protein can enter macrophages and induce macrophage inflammatory response through the NOD2/RIP2/NF-κB pathway. Notably, the region spanning amino acids 13–90 was identified as a critical region necessary for DUF16-induced inflammation. This research not only broadens our comprehension of the recognition process of the intracellular receptor NOD2, but also deepens our understanding of the development of M. pneumoniae infection.
Exploring the potential of Bacillus for crop productivity and sustainable solution for combating rice false smut disease
Authors: Pandey Neha , Vaishnav Richa , Rajavat Asha Singh , Singh Arvind Nath , Kumar Sanjay , Tripathi Ravi Mani , Kumar Madan , Shrivastava Neeraj
Published: May 2024

Rice false smut, which is caused by the soil-borne fungal pathogen Ustilaginoidea virens (U. virens), is one of the most threatening diseases in most of the rice-growing countries including India that causes 0.5–75% yield loss, low seed germination, and a reduction in seed quality. The assessment of yield loss helps to understand the relevance of disease severity and facilitates the implementation of appropriate management strategies. This study aimed to mitigate biotic stress in rice by employing a rhizobacterial-based bioformulation, which possesses diverse capabilities as both a plant growth promoter and a biocontrol agent against U. virens. Rhizobacteria were isolated from the soil of the rice rhizospheres from the healthy plant of the false smut affected zone. Furthermore, they were identified as Bacillus strains: B. subtilis (BR_4), B. licheniformis (BU_7), B. licheniformis (BU_8), and B. vallismortis (KU_7) via sequencing. Isolates were screened for their biocontrol potential against U. virens under in vitro conditions. The antagonistic study revealed that B. vallismortis (KU_7) inhibited U. virens the most (44.6%), followed by B. subtilis BR_4 (41.4%), B. licheniformis BU_7 (39.8%), and B. licheniformis BU_8 (43.5%). Various biochemical and plant growth promoting attributes, such as phosphate and Zn solubilization, IAA, ammonium, siderophore, and chitinase production, were also investigated for all the selected isolates. Furthermore, the potential of the isolates was tested in both in vitro and field conditions by employing talc-based bioformulation through bio-priming and root treatment. The application of bioformulation revealed a 20% decrease in disease incidence in plants treated with B. vallismortis (KU_7), a 60.5% increase in the biological yield, and a 45% increase in the grain yield. This eco-friendly approach not only controlled the disease but also improved the grain quality and reduced the chaffiness.
Transforming growth factor-β1 protects mechanically injured cortical murine neurons by reducing trauma-induced autophagy and apoptosis
Authors: Li Yanlei , Deng Huixiong , Zhang Hengyao , Yang Lin , Wang Shenmiao , Wang Haoyang , Zhu Jiacheng , Li Xiaoning , Chen Xiaoxuan , Lin Yinhong , Li Rui , Wang Gefei , Li Kangsheng
Published: May 2024

Transforming growth factor β1 (TGF-β1) has a neuroprotective function in traumatic brain injury (TBI) through its anti-inflammatory and immunomodulatory properties. However, the precise mechanisms underlying the neuroprotective actions of TGF-β1 on the cortex require further investigation. In this study, we were aimed to investigate the regulatory function of TGF-β1 on neuronal autophagy and apoptosis using an in vitro primary cortical neuron trauma-injury model. LDH activity was assayed to measure cell viability, and intracellular [Ca2+] was measured using Fluo-4-AM in an in vitro primary cortical neuron trauma-injury model. RNA-sequencing (RNAseq), immunofluorescent staining, transmission electron microscopy (TEM), western blot and CTSD activity detection were employed. We observed significant enrichment of DEGs related to autophagy, apoptosis, and the lysosome pathway in trauma-injured cortical neurons. TEM confirmed the presence of autophagosomes as well as autophagolysosomes. Western blot revealed upregulation of autophagy-related protein light chain 3 (LC3-II/LC3-I), sequestosome 1 (SQSTM1/p62), along with apoptosis-related protein cleaved-caspase 3 in trauma-injured primary cortical neurons. Furthermore, trauma-injured cortical neurons showed an upregulation of lysosomal marker protein (LAMP1) and lysosomal enzyme mature cathepsin D (mCTSD), but a decrease in the activity of CTSD enzyme. These results indicated that apoptosis was up-regulated in trauma- injured cortical neurons at 24 h, accompanied by lysosomal dysfunction and impaired autophagic flux. Notably, TGF-β1 significantly reversed these changes. Our results suggested that TGF-β1 exerted neuroprotective effects on trauma- injured cortical neurons by reducing lysosomal dysfunction, decreasing the accumulation of autophagosomes and autophagolysosomes, and enhancing autophagic flux.
Complementary and alternative medicine use in migraine patients: results from a national patient e-survey
Authors: Makarevičius Gytis , Dapkutė Austėja , Ryliškienė Kristina
Published: May 2024

Object

This cross-sectional study aims to investigate migraineurs’ preferred complementary and alternative medicine (CAM) types and the factors influencing their usage.

Materials and methods

An anonymous e-survey was distributed to Lithuanian Migraine Association members, and social media migraine support communities. The collected data consisted of demographic, migraine-related questions, personal qualities, CAM habits.

Results

470 respondents were analyzed. 95.96% were women with a median age of 37 (IQR 31, 44). The median duration of migraine was 17.5 years (IQR 10, 25) and the median headache severity was rated 8 (IQR 7, 10) out of 10. 68.90% of participants had one or more headache days per week. 71.49% of respondents were triptan users, 27.66% used medical prophylaxis, and 17.87% used monoclonal antibodies. 52.55% of respondents used CAM in the past 12 months. Physical activity (36.17%), dietary changes/fasting (27.02%), relaxation/meditation (26.60%) were the most used CAM types. Reasons for CAM use included dissatisfaction with conventional treatment effectiveness (42.51%), concerns about safety (48.18%) and adverse effects (37.25%). Factors associated with the decision to explore CAM included longer headache duration (p = 0.017, Mann–Whitney U test), frequent sick leaves (p < 0.001, Mann–Whitney U test), current preventive medication use (p = 0.016, chi-square test), positive views on CAM safety/naturality (p = 0.001/ p < 0.001, Mann–Whitney U test), belief of having a healthy diet (p < 0.001, chi-square test), food-related worries (p = 0.011, Mann–Whitney U test) and Big-five personality trait of openness to experience (p = 0.049, chi-square test). After logistic regression, the frequent need to take sick leaves, having a healthy diet, food-associated fears maintained statistical significance. CAM use was not associated with non-adherence to conventional medicine. 48.99% of CAM consumers disclosed CAM use to their doctors.

Conclusion

CAM is explored by a significant proportion of migraineurs, less than half communicate this to their doctors. In our sample, physical activity, dietary changes, and relaxation techniques were the most common. Many patients opted for CAM due to previously experienced side effects/ineffectiveness of conventional migraine treatment or the fear of potential harm from standard medication. Individual factors, such as openness of personality can be an important contributing factor.
Outcome of emergency neurosurgery in patients with refractory and super-refractory status epilepticus: a systematic review and individual participant data meta-analysis
Authors: Niazi Farbod , Han Aline , Stamm Lauren , Shlobin Nathan A. , Korman Catherine , Hoang Thien S. , Kielian Agnieszka , Du Pont-Thibodeau Genevieve , Ducharme Crevier Laurence , Major Philippe , Nguyen Dang K. , Bouthillier Alain , Ibrahim George M. , Fallah Aria , Hadjinicolaou Aristides , Weil Alexander G.
Published: May 2024

Background

Refractory (RSE) and super-refractory status epilepticus (SRSE) are serious neurological conditions requiring aggressive management. Beyond anesthetic agents, there is a lack of evidence guiding management in these patients. This systematic review and individual participant data meta-analysis (IPDMA) seeks to evaluate and compare the currently available surgical techniques for the acute treatment of RSE and SRSE.

Methods

A systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Individual Participant Data (PRISMA-IPD). Only patients who underwent surgery while in RSE and SRSE were included. Descriptive statistics were used to compare various subgroups. Multivariable logistic regression models were constructed to identify predictors of status epilepticus (SE) cessation, long-term overall seizure freedom, and favorable functional outcome (i.e., modified Rankin score of 0–2) at last follow-up.

Results

A total of 87 studies including 161 participants were included. Resective surgery tended to achieve better SE cessation rate (93.9%) compared to non-resective techniques (83.9%), but this did not reach significance (p = 0.071). Resective techniques were also more likely to achieve seizure freedom (69.1% vs. 34.4%, p = <0.0001). Older age at SE (OR = 1.384[1.046–1.832], p = 0.023) was associated with increased likelihood of SE cessation, while longer duration of SE (OR = 0.603[0.362–1.003], p = 0.051) and new-onset seizures (OR = 0.244[0.069–0.860], p = 0.028) were associated with lower likelihood of SE cessation, but this did not reach significance for SE duration. Only shorter duration of SE prior to surgery (OR = 1.675[1.168–2.404], p  = 0.0060) and immediate termination of SE (OR = 3.736 [1.323–10.548], p = 0.014) were independently associated with long-term seizure status. Rates of favorable functional outcomes (mRS of 0–2) were comparable between resective (44.4%) and non-resective (44.1%) techniques, and no independent predictors of outcome were identified.

Conclusion

Our findings suggest that emergency neurosurgery may be a safe and effective alternative in patients with RSE/SRSE and may be considered earlier during the disease course. However, the current literature is limited exclusively to small case series and case reports with high risk of publication bias. Larger clinical trials assessing long-term seizure and functional outcomes are warranted to establish robust management guidelines.
Efficacy of a new immunonutrition formula with extra virgin olive oil in the reduction of complications in surgeries of upper digestive tract tumors
Authors: Villar-Taibo Rocío , Vidal-Casariego Alfonso , Santamaría-Nieto Alicia , Cantón-Blanco Ana , Crujeiras Ana B. , Lugo Rodríguez Gloria , Rodríguez-Carnero Gemma , Pita Gutiérrez Francisco , Fernández Pombo Antía , Díaz-López Everardo , Román Eyo Andrea , Rodríguez Lavandeira Uxía , Pena-Dubra Alberto , Martínez-Olmos Miguel Ángel
Published: May 2024

Background

To demonstrate whether a nutritional supplement enriched with arginine, nucleotides, omega-3 fatty acids, and extra virgin olive oil reduces postoperative complications in patients with tumors in the upper digestive tract.

Methods

A randomized, controlled, double-blind, multicenter clinical trial, in which a new immunomodulatory formula with extra virgin olive oil was compared with a standard isoprotein and isoenergetic formula. Patients with gastric, esophageal or biliopancreatic tumors were recruited to receive two units of immunomodulatory formula or control, 5 days before the surgical intervention.

Results

A total of 119 patients were recruited. There was a significant reduction in the number of reinterventions (7.7 vs. 20.4%; p = 0.044) in the intervention group. There was a significant reduction in the development of fistulas in patients with phase angles >5.7°. Also, there were fewer readmissions after biliopancreatic surgeries (0.0 vs. 100%; p = 0.014). The length of hospital stay was similar between groups; however, with the immunomodulatory formula, the patients exhibited greater phase angle at the end of follow-up.

Conclusion

The immunomodulatory formula with extra virgin olive oil administered 5 days before surgery for stomach, esophageal and biliopancreatic tumors improved cellular health and reduced postoperative complications.

Clinical trial registration: [https://clinicaltrials.gov/], identifier [NCT04027088].
Dissection of the signal transduction machinery responsible for the lysyl oxidase-like 4-mediated increase in invasive motility in triple-negative breast cancer cells: mechanistic insight into the integrin-β1-NF-κB-MMP9 axis
Authors: Jiang Fan , Chen Youyi , Tomonobu Nahoko , Kinoshita Rie , Komalasari Ni Luh Gede Yoni , Kasano-Camones Carlos Ichiro , Ninomiya Kazumi , Murata Hitoshi , Yamamoto Ken-ichi , Gohara Yuma , Ochi Toshiki , Ruma I Made Winarsa , Sumardika I Wayan , Zhou Jin , Honjo Tomoko , Sakaguchi Yoshihiko , Yamauchi Akira , Kuribayashi Futoshi , Futami Junichiro , Kondo Eisaku , Inoue Yusuke , Toyooka Shinichi , Sakaguchi Masakiyo
Published: May 2024

Background

Triple-negative breast cancer (TNBC) cells are a highly formidable cancer to treat. Nonetheless, by continued investigation into the molecular biology underlying the complex regulation of TNBC cell activity, vulnerabilities can be exposed as potential therapeutic targets at the molecular level. We previously revealed that lysyl oxidase-like 4 (LOXL4) promotes the invasiveness of TNBC cells via cell surface annexin A2 as a novel binding substrate of LOXL4, which promotes the abundant localization of integrin-β1 at the cancer plasma membrane. However, it has yet to be uncovered how the LOXL4-mediated abundance of integrin-β1 hastens the invasive outgrowth of TNBC cells at the molecular level.

Methods

LOXL4-overexpressing stable clones were established from MDA-MB-231 cells and subjected to molecular analyses, real-time qPCR and zymography to clarify their invasiveness, signal transduction, and matrix metalloprotease (MMP) activity, respectively.

Results

Our results show that LOXL4 potently promotes the induction of matrix metalloprotease 9 (MMP9) via activation of nuclear factor-κB (NF-κB). Our molecular analysis revealed that TNF receptor-associated factor 4 (TRAF4) and TGF-β activated kinase 1 (TAK1) were required for the activation of NF-κB through Iκβ kinase kinase (IKKα/β) phosphorylation.

Conclusion

Our results demonstrate that the newly identified LOXL4-mediated axis, integrin-β1-TRAF4-TAK1-IKKα/β-Iκβα-NF-κB-MMP9, is crucial for TNBC cell invasiveness.
Clinicopathological characteristics and fertility preserving treatment of atypical polypoid adenomyoma
Authors: Wang Qian , Shan Weiwei , Yang Bingyi , Xue Yu , Lou Yaochen , Chen Xiaojun
Published: May 2024

Objective

Atypical polypoid adenomyoma (APA) is a rare benign tumor frequently diagnosed in young women that may coexist with or progress to atypical endometrial hyperplasia (EAH) or endometrioid endometrial carcinoma (EEC). This study aimed to investigate which subset of patients with APA are prone to concurrent or subsequent EAH or EEC, evaluate the necessity of progestin treatment in patients with APA only after achieving a complete response (CR) through hysteroscopic lesion resection, and assess the impact of concurrent APA on the fertility-preserving treatment of EAH or EEC.

Methods

This retrospective single-center study analyzed 86 patients with APA treated at the Obstetrics and Gynecology Hospital of Fudan University between January 2010 and October 2021. Patients with EAH or EEC only who underwent fertility-preserving treatment during the same period were matched in a 2:1 ratio with patients with concurrent APA and EAH or EEC. The clinicopathological characteristics, treatments, and prognosis were analyzed.

Results

The median patient age was 31 years (range 21–47 years). Among the 86 included patients, nine underwent total hysterectomy, 62 received conservative treatment, and the remaining 15 were lost to follow-up. A comparison of the 16 patients with APA only versus the 58 patients with APA and concurrent or subsequent EAH or EEC revealed that a homeostasis model assessment of insulin resistance (HOMA-IR) of > 2.2 (P = 0.047) and high-density lipoprotein (HDL) concentration of < 1.2 mmol/L (P = 0.028) were independent risk factors for EAH or EEC in patients with APA. Among the 17 patients with APA only who received conservative treatment and achieved a CR after hysteroscopic lesion resection, 13 received hormone treatment for a median duration of 6.3 months. The median follow-up time for these 17 patients was 49.0 months, during which no recurrence of APA was observed, but six patients developed endometrial hyperplastic diseases. Regarding the impact of concurrent APA on fertility-preserving treatment for EAH or EEC, the median time to achieve a CR was 24.0 weeks (95% confidence interval [CI]: 23.0–40.4) in the APA group and 26.0 weeks (95% CI: 24.3–32.3) in the non-APA group (P = 0.424). There were no significant differences between the two groups in the outcomes of fertility-preserving treatment.

Conclusion

Patients with APA only may still develop endometrial hyperplastic diseases after complete resection of the lesion under hysteroscopy to achieve a CR, particularly those with a HOMA-IR of > 2.2 or HDL concentration of < 1.2 mmol/L. Concurrent APA did not affect the efficacy of fertility-preserving treatment in patients with EAH or EEC.
Advances in CAR-NK cell therapy for lung cancer: is it a better choice in the future?
Authors: Liu Fengqin , Miao Xia , Han Lu , Song Xiao
Published: May 2024

Lung cancer remains one of the leading causes of cancer-related mortality worldwide necessitating the development of innovative therapeutic strategies. Chimeric antigen receptor (CAR) natural killer (NK) cell therapy represents a promising advancement in the field of oncology offering a novel approach to target and eliminate tumor cells with high specificity and reduced risk of immune-related adverse effects. This paper reviews the mechanism, potential targets, and recent advances in CAR-NK cell therapy for lung cancer, including the design and engineering of CAR-NK cells, preclinical studies, and the outcomes of early-phase clinical trials. We highlight the unique advantages of using NK cells, such as their innate ability to recognize and kill cancer cells and their reduced potential for inducing graft-versus-host disease (GvHD) and cytokine release syndrome (CRS) compared to CAR T-cell therapies. Results from recent studies demonstrate significant antitumor activity in lung cancer models with improved targeting and persistence of CAR-NK cells observed in vitro and in vivo. Finally, we discuss the challenges in optimizing CAR-NK cell therapies, including the potential resistance mechanisms. The paper concludes with an outlook on the future directions of CAR-NK cell research and its implications for lung cancer treatment emphasizing the importance of continued innovation and collaboration in the field.
Avelumab maintenance therapy for node-positive muscle invasive bladder cancer: a report of two cases
Authors: Poon Darren M. C. , Ho Lap Yin , Kwong Yiu Ming
Published: May 2024

Background

Muscle-invasive bladder cancer (MIBC) with nodal involvement is associated with poor prognosis and high mortality. Treatment of node-positive MIBC is complex due to disease heterogeneity and a lack of evidence-based treatment options, especially alternatives to radical cystectomy. We describe a bladder-sparing management approach involving systemic therapy followed by maintenance therapy, illustrated with two cases of node-positive MIBC.

Case presentation

Two patients with node-positive MIBC received upfront gemcitabine/cisplatin chemotherapy, concurrent chemoradiotherapy (cCRT), and avelumab (immune checkpoint inhibitor) maintenance therapy. Both patients achieved complete remission without recurrence or distant metastasis post-avelumab maintenance therapy. At the last follow-up, Patient 1 (45-year-old male) was in remission for over two years, and Patient 2 (57-year-old male) was in complete remission for over one year post-chemotherapy. Avelumab treatment was well-tolerated, with no immune-related adverse events, and quality of life (QoL) was maintained.

Conclusion

Both cases showed a good response and extended remission on avelumab maintenance, supporting its use in conjunction with local consolidation therapy as a bladder-preserving approach in node-positive MIBC. Further research, such as the ongoing INSPIRE trial, is required to refine treatment strategies for this patient group.
Laparoscopic nephron-sparing surgery for complex renal cystic lesions: a single-center experience
Authors: Dong Dexin , Zhang Yushi
Published: May 2024

Objectives

This study aimed to explore the feasibility and safety of laparoscopic nephron-sparing surgery (LNSS) for complex renal cystic lesions.

Methods

A retrospective study was conducted on 83 cases of complex renal cystic lesions treated with LNSS in our hospital. There were 32 men and 51 women, ranging in age from 24 to 73 years (average, 47.22 ± 9.03 years). The diameter of the cysts was 1.5–5.9 cm (average, 3.44 ± 0.86cm). According to the Bosniak classification, there were 15 cases of type II, 23 cases of type IIF, 29 cases of type III, and 16 cases of type IV complex renal cystic lesions. According to clinical classification based on the difficulty of laparoscopic partial nephrectomy and the depth of the lesion, the 83 complex renal cystic lesions were divided into 48 cases of the extra-renal type, 15 cases of the centrally located type, seven cases of the renal sinus type, and 13 cases of the renal hilum type.

Results

Laparoscopic partial nephrectomy was successful in all 83 patients. The surgical time was 35–102 min (average, 52.13 ± 14.38 min), the intraoperative bleeding volume was 10–200 ml (average, 27.25 ± 12.26 ml), and the renal artery occlusion time was 12–28 min (average, 12.46 ± 4.45 min). There was no significant change in creatinine before and after surgery. The postoperative pathological results showed 71 cases of renal clear cell carcinoma, five cases of low malignant potential multilocular cystic renal tumors, and seven cases of pure renal cysts with all margins negative.

Conclusions

There is potential for the malignant transformation of complex renal cysts into renal cell carcinoma. For complex renal cysts classified as Bosniak IIF or higher, surgical intervention is recommended, and LNSS is safe and effective. The complexity of the surgical procedure varies depending on the location classification of the complex renal cysts.
Clinical value of serum tumor markers in assessing the efficacy of neoadjuvant chemotherapy in advanced ovarian cancer: single-center prospective clinical study
Authors: Huang Jing , Du Danyi , Chen Hailong , Luo Deping , Wang Qi , Li Chan , Li Yuanxiang , Yu Ying
Published: May 2024

Objective

This study aimed to assess the clinical importance of various biomarkers, including NLR, CEA, CA199, CA125, CA153, and HE4, through dynamic testing to evaluate the effectiveness of neoadjuvant chemotherapy (NACT) for individuals facing advanced ovarian cancer. This provides valuable information for tailoring treatment plans to individual patients, thereby leading to a more personalized and effective management of individuals facing ovarian cancer.

Methods

The levels of NLR, CA125, CA199, CEA, CA153, and HE4 were detected before chemotherapy and after 3 courses of chemotherapy. Patients were categorized into ineffective and effective groups according to the effectiveness of NACT. To evaluate the factors influencing NACT’s effectiveness in individuals facing advanced ovarian cancer, receiver operating characteristic (ROC) curves, predictive modeling, and multifactorial regression analysis were employed.

Results

In the effective group, the patients’ age, maximum tumor diameter, and CEA and HE4 levels of the patients were significantly higher compared to those in the ineffective group (P <.05). Additionally, the difference in HE4 levels before and after treatment between the effective and ineffective groups was statistically significant (P<.05). Multifactorial analysis showed that age and maximum tumor diameter were independent risk factors impacting the effectiveness of NACT in individuals facing advanced ovarian cancer (P<.05). The ROC curve for predicting the effectiveness of NACT in individuals facing advanced ovarian cancer showed a sensitivity of 93.3% for NLR and a specificity of 92.3% for CA199. HE4 emerged as the most reliable predictor, demonstrating a specificity of 84.6% and a sensitivity of 75.3%. The area under the curve of the combined CA125 and HE4 assays for predicting the ineffectiveness of NACT in individuals facing advanced ovarian cancer was 0.825, showcasing a specificity of 74.2% and a sensitivity of 84.6%.

Conclusion

The predictive capacity for the effectiveness of NACT in individuals facing advanced ovarian cancer is notably high when considering the sensitivity of NLR and the specificity of CA199. Additionally, the combination of CA125 and HE4 assays can obtain a better predictive effect, which can accurately select patients suitable for NACT, determine the appropriate timing of the interval debulking surgery (IDS) surgery, and achieve a satisfactory tumor reduction effect.
Primary cervicothoracic melanoma of spinal cord: a case report and literature review
Authors: Dang Ying , Du Aichao , Wei Wenyuan , Xue Jungang
Published: May 2024

A 53-year-old male patient presented progressive numbness and weakness in the right limbs for a 2-year duration. Magnetic resonance imaging scans revealed an intramedullary lesion crossed over cervical and thoracic levels accompanied by syringomyelia at the proximal end of the lesion. The patient underwent subtotal resection of the neoplasm. The histological findings of the tumor were consistent with primary intramedullary malignant melanoma and not initial ependymoma after careful dermatologic and ophthalmologic re-examination. Primary melanoma of the spinal cord, particularly cervicothoracic localization with syringomyelia, is seldom reported in the literature. We report a case of this uncommon tumor and also discuss the clinical course, diagnosis, and treatment.