bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vitamin B12, folate, and homocysteine in metabolic syndrome: a systematic review and meta-analysis
Authors: Ulloque-Badaracco Juan R. , Hernandez-Bustamante Enrique A. , Alarcon-Braga Esteban A. , Al-kassab-Córdova Ali , Cabrera-Guzmán Juan C. , Herrera-Añazco Percy , Benites-Zapata Vicente A. 
Published: September 2023

Background &amp; aimsMetabolic syndrome (MetS) is associated with life-threatening conditions. Several studies have reported an association of vitamin B12, folic acid, or homocysteine (Hcy) levels with MetS. This systematic review and meta-analysis assessed the association of vitamin B12, folic acid, and Hcy levels with MetS.MethodsPubMed, Scopus, Embase, Ovid/Medline, and Web of Science were searched up to February 13, 2023. Cross-sectional, case-control, or cohort studies were included. A random-effects model was performed using the DerSimonian and Laird method to estimate the between-study variance. Effect measures were expressed as odds ratios (OR) with their corresponding 95% confidence intervals (95% CI). Between-study heterogeneity was evaluated using Cochran’s Q test and the I2 statistic.ResultsSixty-six articles (n = 87,988 patients) were included. Higher vitamin B12 levels were inversely associated with MetS (OR = 0.87; 95% CI: 0.81–0.93; p &lt; 0.01; I2 = 90%). Higher Hcy levels were associated with MetS (OR = 1.19; 95% CI: 1.14–1.24; p &lt; 0.01; I2 = 90%). Folate levels were not associated with MetS (OR = 0.83; 95% CI: 0.66–1.03; p = 0.09; I2 = 90%).ConclusionHigher vitamin B12 levels were inversely associated with MetS, whereas higher Hcy levels were associated with MetS. Studies assessing the pathways underlying this association are required.
Oral semaglutide improves body composition and preserves lean mass in patients with type 2 diabetes: a 26-week prospective real-life study
Authors: Volpe Sara , Lisco Giuseppe , Fanelli Margherita , Racaniello Davide , Colaianni Valentina , Lavarra Valentina , Triggiani Domenico , Crudele Lucilla , Triggiani Vincenzo , Sabbà Carlo , De Pergola Giovanni , Piazzolla Giuseppina 
Published: September 2023

BackgroundOral semaglutide is the first glucagon-like peptide-1 receptor agonist (GLP-1RA) designed for oral administration; it offers a promising opportunity to facilitate an early approach to Type 2 Diabetes (T2D). The study aimed to evaluate, in a real-life setting, the effects of oral semaglutide on the body composition of patients with T2D after 26 weeks of therapy.MethodsThirty-two patients with T2D were evaluated at baseline (T0) and after three (T3) and six (T6) months of therapy with oral semaglutide. At each time point, body composition was assessed using a phase sensitive bioimpedance analyzer. Clinical, anthropometric and laboratory parameters, and the main biometric surrogates of liver steatosis and fibrosis, were also analyzed and compared.ResultsA significant and early reduction in anthropometric and glucometabolic parameters, alanine aminotransferase, Fatty Liver Index, and Fat Mass was observed. Visceral Adipose Tissue (VAT) decreased, while Fat Free Mass and Skeletal Muscle Mass (SMM) were preserved during therapy, resulting in a beneficial increase in the SMM/VAT ratio. Finally, an overall improvement in body fluid distribution was observed.ConclusionOur real-world data confirm the clinical efficacy of oral semaglutide and highlight its ability to improve the nutritional status of patients with T2D.
PyCreas: a tool for quantification of localization and distribution of endocrine cell types in the islets of Langerhans
Authors: Asuaje Pfeifer Melissa , Langehein Hans , Grupe Katharina , Müller Steffi , Seyda Joana , Liebmann Moritz , Rustenbeck Ingo , Scherneck Stephan 
Published: September 2023

Manifest diabetes, but also conditions of increased insulin resistance such as pregnancy or obesity can lead to islet architecture remodeling. The contributing mechanisms are as poorly understood as the consequences of altered cell arrangement. For the quantification of the different cell types but also the frequency of different cell-cell contacts within the islets, different approaches exist. However, few methods are available to characterize islet cell distribution in a statistically valid manner. Here we describe PyCreas, an open-source tool written in Python that allows semi-automated analysis of islet cell distribution based on images of pancreatic sections stained by immunohistochemistry or immunofluorescence. To ensure that the PyCreas tool is suitable for quantitative analysis of cell distribution in the islets at different metabolic states, we studied the localization and distribution of alpha, beta, and delta cells during gestation and prediabetes. We compared the islet cell distribution of pancreatic islets from metabolically healthy NMRI mice with that of New Zealand obese (NZO) mice, which exhibit impaired glucose tolerance (IGT) both preconceptionally and during gestation, and from C57BL/6 N (B6) mice, which acquire this IGT only during gestation. Since substrain(s) of the NZO mice are known to show a variant in the Abcc8 gene, we additionally examined preconceptional SUR1 knock-out (SUR1-KO) mice. PyCreas provided quantitative evidence that alterations in the Abcc8 gene are associated with an altered distribution pattern of islet cells. Moreover, our data indicate that this cannot be a consequence of prolonged hyperglycemia, as islet architecture is already altered in the prediabetic state. Furthermore, the quantitative analysis suggests that states of transient IGT, such as during common gestational diabetes mellitus (GDM), are not associated with changes in islet architecture as observed during long-term IGT. PyCreas provides the ability to systematically analyze the localization and distribution of islet cells at different stages of metabolic disease to better understand the underlying pathophysiology.
A rare case of mosaic Klinefelter syndrome in a 45-year-old man leading to successful live birth through ejaculated spermatozoa: a case report and literature review
Authors: Elzeiny Hossam , Agresta Franca , Stevens John , Gardner David K. 
Published: September 2023

Background: Men diagnosed with Klinefelter syndrome (KS) commonly exhibit non-obstructive azoospermia or rarely having sperm in their ejaculate, rendering them traditionally considered sterile prior to the introduction of intracytoplasmic sperm injection (ICSI). The presence of mosaic KS may mask the classical phenotype, resulting in underdiagnosis throughout their lifetime. Surgical sperm retrieval through Microdissection Testicular Sperm Extraction (Micro-TESE) combined with ICSI has become the gold standard approach, maximizing reproductive outcomes in these individuals. However, it is noteworthy that approximately 7% of men with KS may exhibit sperm in their ejaculate, providing an opportunity for them to achieve biological parenthood through ICSI.Case Presentation: In this report, we present an exceptional case of a 45-year-old man with Mosaic KS and severe oligozoospermia who successfully achieved pregnancy utilizing ICSI with freshly ejaculated sperm. Remarkably, this case represents the oldest recorded instance of a man with Klinefelter syndrome fathering his own biological child using sperm derived from fresh ejaculate.Conclusion: Although this case is exceedingly rare, it underscores the critical importance of exhausting all possibilities to facilitate biological parenthood in men with KS before considering alternative options such as sperm donation or adoption. By recognizing the potential for successful conception using ejaculated sperm in this population, we can provide individuals with mosaic KS the opportunity to fulfill their desire for biological offspring.
Human leukocyte antigen association in systemic sclerosis patients: our experience at a tertiary care center in North India
Authors: Machhua Sanghamitra , Sharma Shefali Khanna , Kumar Yashwant , Singh Surjit , Aggarwal Ritu , Anand Shashi , Kumar Manoj , Singh Heera , Minz Ranjana Walker 
Published: September 2023

IntroductionSystemic sclerosis (SSc) is a chronic multisystem autoimmune rheumatic disease of unknown etiology. Several studies have established that SSc is triggered by a dynamic interplay between genetic factors and environmental stimuli. In the present study, we aimed to study the association of human leukocyte antigen (HLA) with familial and non-familial SSc patients [limited cutaneous SSc (lcSSc) and diffuse cutaneous SSc (dcSSc)] from North India.MethodsThe HLA-A, B, DRB1, and DQB1 genotyping of 150 (70 lcSSc and 80 dcSSc) adult-onset SSc patients and 150 age-gender-matched healthy controls were performed with sequence-specific oligonucleotide (SSO) typing kits using the luminex platform. HLA typing for HLA class I (A, B, and C) and II (DRB1, DQB1, and DPB1) in five North Indian families consisting of parent–child/sibling pairs affected with SSc or overlap syndrome was performed by Next Generation Sequencing (NGS) with Illumina MiniSeq.RseultsAmong the non-familial SSc patients, HLA- DRB1*11 (P = 0.001, OR: 2.38, Pc = 0.01) was identified as a risk allele, and DRB1*12 (P = .0001, OR: 0.00, Pc = 0.001) as a protective allele. There was no statistical association found with HLA-DQB1*. Also, no significant association was observed between HLA antigens and different clinical subsets (lcSSc and dcSSc) of SSc. Two cases of familial SSc patients had the DRB1*11 allele. The DRB1*12 allele was absent in all the familial SSc patients. DiscussionHLA DRB1*11 (risk allele) and DRB1*12 (protective allele) were found to be strongly associated with non-familial SSc patients and partially explain the disease’s familial clustering, supporting the susceptible genetic background theory for SSc development. The study also indicates the HLA allele as a common genetic risk factor in distinct autoimmune diseases contributing to overlap syndrome or polyautoimmunity.
AURKA inhibitor-induced PD-L1 upregulation impairs antitumor immune responses
Authors: Meng Bi , Zhao Xuan , Jiang Shuchang , Xu Zijian , Li Sijin , Wang Xu , Ma Wen , Li Liantao , Liu Dan , Zheng Junnian , Peng Hui , Shi Ming 
Published: September 2023

IntroductionTumor immunotherapy targeting PD-L1 has emerged as one of the powerful tools for tumor therapy. Numerous studies indicate that tumor-targeted drugs critically have an influence on the interaction between the immune system and tumors by changing the expression of PD-L1, which is beneficial for immunotherapy. Our study provided novel evidence for improving the drug regimen in tumor targeted therapy and immunotherapy.MethodsThe expression of PD-L1 on SKBR3, MDA-MB-231, MCF7, 4T1, MC38 and B16 cells was evaluated by flow cytometry after treatment with six preclinical targeted drugs (ARN-509, AZD3514, Galeterone, Neratinib, MLN8237 and LGK974). AURKA was knockdowned by using the specific siRNA or CRISPR-Cas9 technology. In the 4T1-breast tumor and colorectal cancer xenograft tumor models, we determined the number of infiltrated CD3+ and CD8+ T cells in tumor tissues by IHC.ResultsWe found that AURKA inhibitor MLN8237 promoted the expression of PD-L1 in a time- and concentration-dependent manner while exerted its antitumor effect. Knockdown of AURKA could induce the upregulation of PD-L1 on SKBR3 cells. MLN8237-induced PD-L1 upregulation was mainly associated with the phosphorylation of STAT3. In the 4T1-breast tumor xenograft model, the infiltrated CD3+ and CD8+ T cells decreased after treatment with MLN8237. When treated with MLN8237 in combination with anti-PD-L1 antibody, the volumes of tumor were significantly reduced and accompanied by increasing the infiltration of CD3+ and CD8+ T cells in colorectal cancer xenograft tumor model.DiscussionOur data demonstrated that MLN8237 improved the effect of immunology-related therapy on tumor cells by interacting with anti-PD-L1 antibody, which contributed to producing creative sparks for exploring the possible solutions to overcoming drug resistance to tumor targeted therapy.
Relapsing polychondritis: focus on cardiac involvement
Authors: Yin Ruxue , Zhao Mengzhu , Xu Dong , Wang Qian , Li Mengtao , Zhang Wen , Zhang Fengchun , Zeng Xiaofeng , Huo Yuping , Hou Yong 
Published: September 2023

BackgroundRelapsing polychondritis (RP) with cardiac involvement may present with acute cardiovascular events, and may be associated with a negative prognosis. Herein, we analyzed the clinical characteristics of RP patients with cardiac involvement.MethodRP patients, hospitalized from December 2005 to December 2021 at Peking Union Medical College Hospital (PUMCH), were screened. Univariate and multivariate logistic regression analyses were used to statistically analyze the clinical characteristics of these patients.ResultsThe incidence of cardiac involvement in inpatients with RP was 24.1%. Univariate logistic regression analysis revealed age, central nervous system (CNS) involvement, neutrophil-to-lymphocyte ratio (NLR) &gt; 6.41, and disease duration &gt; 4 years as risk factors for cardiac involvement in RP. Conversely, the incidence of tracheobronchial and chest wall involvement was significantly lower in the group with cardiac involvement. Multivariate logistic regression confirmed that age, CNS involvement, NLR &gt; 6.41, and disease duration &gt; 4 years were independent factors for cardiac involvement. Subsequently, we identified five well-defined clinical patterns of RP, based on the involvement of different organs in our patients, and found that the heart-brain model was significantly mutually exclusive with the airway model.ConclusionOccurrence of cardiac involvement in RP is associated with age, CNS involvement, NLR, and disease duration. It is mutually exclusive with airway-related involvement. Regular echocardiography and electrocardiography are necessary for patients with RP.
Rare variants in complement system genes associate with endothelial damage after pediatric allogeneic hematopoietic stem cell transplantation
Authors: Leimi Lilli , Koski Jessica R. , Kilpivaara Outi , Vettenranta Kim , Lokki A. Inkeri , Meri Seppo 
Published: September 2023

IntroductionComplement system has a postulated role in endothelial problems after hematopoietic stem cell transplantation (HSCT). In this retrospective, singlecenter study we studied genetic complement system variants in patients with documented endotheliopathy. In our previous study among pediatric patients with an allogeneic HSCT (2001-2013) at the Helsinki University Children´s Hospital, Finland, we identified a total of 19/122 (15.6%) patients with vascular complications, fulfilling the criteria of capillary leak syndrome (CLS), venoocclusive disease/sinusoidal obstruction syndrome (VOD/SOS) or thrombotic microangiopathy (TMA).MethodsWe performed whole exome sequencing (WES) on 109 patients having an adequate pre-transplantation DNA for the analysis to define possible variations and mutations potentially predisposing to functional abnormalities of the complement system. In our data analysis, we focused on 41 genes coding for complement components.Results50 patients (45.9%) had one or several, nonsynonymous, rare germline variants in complement genes. 21/66 (31.8%) of the variants were in the terminal pathway. Patients with endotheliopathy had variants in different complement genes: in the terminal pathway (C6 and C9), lectin pathway (MASP1) and receptor ITGAM (CD11b, part of CR3). Four had the same rare missense variant (rs183125896; Thr279Ala) in the C9 gene. Two of these patients were diagnosed with endotheliopathy and one with capillary leak syndrome-like problems. The C9 variant Thr279Ala has no previously known disease associations and is classified by the ACMG guidelines as a variant of uncertain significance (VUS). We conducted a gene burden test with gnomAD Finnish (fin) as the reference population. Complement gene variants seen in our patient population were investigated and Total Frequency Testing (TFT) was used for execution of burden tests. The gene variants seen in our patients with endotheliopathy were all significantly (FDR &lt; 0.05) enriched compared to gnomAD. Overall, 14/25 genes coding for components of the complement system had an increased burden of missense variants among the patients when compared to the gnomAD Finnish population (N=10 816).DiscussionInjury to the vascular endothelium is relatively common after HSCT with different phenotypic appearances suggesting yet unidentified underlying mechanisms. Variants in complement components may be related to endotheliopathy and poor prognosis in these patients.
Lower levels of FOXP3 are associated with prolonged inflammatory responses in kidney transplant recipients
Authors: Saleh Qais W. , Mohammadnejad Afsaneh , Tepel Martin 
Published: September 2023

BackgroundImmunosuppressive treatment of kidney transplant recipients is mainly aimed at pro-inflammatory T effector cells, yet they also target the immunosuppressive T regulatory cells. Here, we test the hypothesis that low levels of the master gene regulator of T regulatory cells, forkhead box P3 (FOXP3) splice variants, are associated with prolonged inflammatory responses to stimuli.MethodsFrom blood samples obtained the first – and 29th day post-transplant, we extracted peripheral blood mononuclear cells and measured mRNA levels of Total FOXP3, pre-mature RNA FOXP3 (pre-mRNA FOXP3), full length FOXP3 (FOXP3fl) and, FOXP3 splice variant excluding exon two (FOXP3d2). We defined the primary outcome as the number of days in which C reactive protein (CRP) was above 50 mg/L. CRP levels were gathered in two periods, the first from the second to 29 days post-transplant, and the second from 30 to 57 days post-transplant. The association was tested using adjusted negative binomial regression.ResultsFrom 507 included kidney transplant recipients, 382 recipients had at least one CRP measurement &gt;50 mg/L in the first period, median duration of elevated CRP was 4 days [interquartile range (IQR) 2 to 6]. In the second period, 69 recipients had at least one CRP measurement &gt;50 mg/L, median duration of elevated CRP was 3 days [IQR 2 to 5]. In the first period, we found a significant association between lower levels of Total FOXP3 and prolonged duration of CRP elevation, incidence rate ratio 0.61 (95% confidence interval 0.46-0.80), p&lt;0.01.ConclusionLower levels of total FOXP3 mRNA levels in peripheral blood of kidney transplant recipients are associated with prolonged duration of inflammatory responses regardless of the underlying stimuli.
Regulatory T cells are associated with the tumor immune microenvironment and immunotherapy response in triple-negative breast cancer
Authors: Huang Pengfei , Zhou Xinyue , Zheng Minying , Yu Yongjun , Jin Gongsheng , Zhang Shiwu 
Published: September 2023

IntroductionTriple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer with a high risk of distant metastasis, an extremely poor prognosis, and a high risk of death. Regulatory T cells (Tregs) contribute to the formation of a tumor immunosuppressive microenvironment, which plays an important role in the progression and treatment resistance of TNBC.MethodsA public single-cell sequencing dataset demonstrated increased infiltration of Tregs in TNBC tissues relative to normal breast tissue. Weighted gene co-expression network analysis was used to identify Treg infiltration-related modules for METABRIC TNBC samples. Subsequently, we obtained two Treg infiltration-associated clusters of TNBC by applying consensus clustering and further constructed a prognostic model based on this Treg infiltration-associated gene module. The ability of the selected gene in the prognostic model, thymidine kinase-1 (TK1), to promote the progression of TNBC was evaluated in vitro.ResultsWe concluded that two Treg infiltration-associated clusters had different prognoses and sensitivities to drugs commonly used in breast cancer treatment, and multi-omics analysis revealed that the two clusters had different copy number variations of key tumor progression genes. The 7-gene risk score based on TNBC Treg infiltration was a reliable prognostic indicator both in the training and validation cohorts. Moreover, patients with TNBC with high Treg infiltration-related scores lacked the activation of immune activation pathways and exhibited resistance to anti-PD1 immunotherapy. Knocking down TK1 led to impaired proliferation, migration, and invasion of TNBC cells in vitro. In addition, specimens from patients with TNBC with high TK1 expression showed significantly higher Treg infiltration in tumors. Results of spatial transcriptome analysis showed that TK1 positive cells mainly localize in tumor area, and Treg cell infiltration in TNBC tissues was associated with high expression of TK1. Pan-cancer analysis also demonstrated that TK1 is associated with poor prognosis and activation of proliferation pathways in multiple cancers.DiscussionWe established a prognostic model related to Treg infiltration and this model can be used to establish a clinically relevant classification of TNBC progression. Additionally, our work revealed the underestimable potential of TK1 as a tumor biomarker and immunotherapeutic target.
Camera-based automated monitoring of flying insects in the wild (Camfi). II. flight behaviour and long-term population monitoring of migratory Bogong moths in Alpine Australia
Authors: Wallace Jesse Rudolf Amenuvegbe , Dreyer David , Reber Therese Maria Joanna , Khaldy Lana , Mathews-Hunter Benjamin , Green Ken , Zeil Jochen , Warrant Eric 
Published: September 2023

IntroductionThe Bogong moth Agrotis infusa is well known for its remarkable annual round-trip migration from its breeding grounds across eastern and southern Australia to its aestivation sites in the Australian Alps, to which it provides an important annual influx of nutrients. Over recent years, we have benefited from a growing understanding of the navigational abilities of the Bogong moth. Meanwhile, the population of Bogong moths has been shrinking. Recently, the ecologically and culturally important Bogong moth was listed as endangered by the IUCN Red List, and the establishment of a program for long-term monitoring of its population has been identified as critical for its conservation.MethodsHere, we present the results of two years of monitoring of the Bogong moth population in the Australian Alps using recently developed methods for automated wildlife-camera monitoring of flying insects, named Camfi. While in the Alps, some moths emerge from the caves in the evening to undertake seemingly random flights, filling the air with densities in the dozens per cubic metre. The purpose of these flights is unknown, but they may serve an important role in Bogong moth navigation.ResultsWe found that these evening flights occur throughout summer and are modulated by daily weather factors. We present a simple heuristic model of the arrival to and departure from aestivation sites by Bogong moths, and confirm results obtained from fox-scat surveys which found that aestivating Bogong moths occupy higher elevations as the summer progresses. Moreover, by placing cameras along two elevational transects below the summit of Mt. Kosciuszko, we found that evening flights were not random, but were systematically oriented in directions relative to the azimuth of the summit of the mountain. Finally, we present the first recorded observations of the impact of bushfire smoke on aestivating Bogong moths – a dramatic reduction in the size of a cluster of aestivating Bogong moths during the fire, and evidence of a large departure from the fire-affected area the day after the fire.DiscussionOur results highlight the challenges of monitoring Bogong moths in the wild and support the continued use of automated camera-based methods for that purpose.