bluuebunny/crossref_metadata_2025_split 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

BackgroundOvarian 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.ObjectivesThe 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.MethodsA 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.ResultsFor patients &lt;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.ConclusionsIn 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

BackgroundSerum 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.MethodsGenetic data was obtained from the UK Biobank datasets. Causal effects were estimated using multiple MR methods. Heterogeneity and pleiotropy tests were performed.ResultsMR analysis revealed that HDL-C and TG exhibited causal associations with diabetic nephropathy (P&lt;0.05). Similar trends were not observed for other lipid parameters.ConclusionsOur 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 studyThis 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.
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 reportA 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.ConclusionChemotherapy 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

BackgroundThe 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.MethodsAggregate 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.ResultsThere was a potential genetic predisposition association identified between CD39+ CD8br AC, CD39+ CD8br % T cell, and the risk of DLBCL (OR=1.51, p&lt;0.001; OR=1.25, p=0.001) (adjusted FDR&lt;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&gt;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.ConclusionsThere 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

BackgroundNeuronal 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.MethodsThe 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.ResultsThree 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.ConclusionThis 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

IntroductionSomatic 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.MethodsHere, 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.ResultsDeepSHM 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.DiscussionOur 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.
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

ObjectThis cross-sectional study aims to investigate migraineurs’ preferred complementary and alternative medicine (CAM) types and the factors influencing their usage.Materials and methodsAn 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.Results470 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 &lt; 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 &lt; 0.001, Mann–Whitney U test), belief of having a healthy diet (p &lt; 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.ConclusionCAM 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

BackgroundRefractory (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.MethodsA 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.ResultsA 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 = &lt;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.ConclusionOur 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

BackgroundTo 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.MethodsA 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.ResultsA 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 &gt;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.ConclusionThe 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

BackgroundTriple-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.MethodsLOXL4-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.ResultsOur 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.ConclusionOur 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.