bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association between lipoprotein(a) and thromboembolism in patients with non-valvular atrial fibrillation: a cross-sectional study
Authors: Song Jie , Zhang Xiaoxue , Wei Meng , Bo Yakun , Zhou Xianhui , Tang Baopeng 
Published: August 2022

Abstract
Background
Lipoprotein(a) [Lp(a)] is a recognized risk factor for ischemic stroke (IS); however, its role in thromboembolism in patients with non-valvular atrial fibrillation (NVAF) remains controversial. We aimed to assess the association of Lp(a) and IS and systemic embolism (SEE) in NVAF patients.

Methods
In total, 16,357 patients with NVAF were recruited from the First Affiliated Hospital of Xinjiang Medical University from January 1, 2009, to December 31, 2021, and were divided into groups based on Lp(a) quartiles. Logistic regression models analyzed the association between Lp(a), IS, and SEE. The restriction cubic spline was used to assess the potential nonlinear relationship between Lp(a), IS, and SEE. We conducted subgroup analyses and estimated the multiplicative interaction between the stratified variables and Lp(a) to investigate whether the association between Lp(a) and IS and SEE was affected by age, sex, anticoagulants, and CHA2DS2-VASc score.

Results
We identified 1319 IS and 133 SEE events. After correcting for CHA2DS2-VASc score and other potential confounders, each 1-standard deviation (SD) increase in log-Lp(a) was related to a 23% increased risk of IS (odds ratios [OR], 1.23; 95% confidence intervals [CI], 1.07–1.41). NVAF patients in the highest Lp(a) quartile were 1.23-fold more likely to have IS than those in the lowest quartile (OR, 1.23; 95% CI, 1.04–1.45). A positive linear relationship between Lp(a) and IS risk was observed (P for nonlinear = 0.341). In the fully adjusted model, subjects had a 1.78-fold increased risk of SEE for each 1-SD increase in log-Lp(a) (OR, 2.78; 95% CI, 1.78–4.36). Subjects in the highest Lp(a) quartile had a 2.38-fold elevated risk of SEE (OR, 3.38; 95% CI, 1.85–6.19) compared with the lowest quartile. Furthermore, Lp(a) had a nonlinear relationship with the risk of SEE (P for nonlinear = 0.005).

Conclusions
Elevated Lp(a) concentration was significantly associated with IS and SEE, suggesting that Lp(a) may be an emerging biomarker that can help clinicians identify patients at high risk of thromboembolism in this population.
HPV and vaginal microecological disorders in infertile women: a cross-sectional study in the Chinese population
Authors: Wang Li , He Lin , Chen Junyu , Wei Shuyao , Xu Hongzhou , Luo Mengjun 
Published: August 2022

Abstract
Background
The purpose of this study was to evaluate the distributions of vaginal microbiome dysbiosis and human papillomavirus (HPV) subtypes in infertile women and explore the correlations of HPV infection and vaginal microbiome dysbiosis with infertility.

Methods
In total, 1464 women aged 18–50 years were included in this study; 649 participants were included in the infertility group, and 815 participants were included in the normal group. The participants were tested for HPV, and their vaginal microecology was examined. The χ2 test and Spearman regression were used for statistical analysis, and binary logistic regression was performed to identify the risk factors for infertility.

Results
The patients in the infertility group were younger than those in the normal group, and the proportions of bacterial vaginosis and vaginal imbalance in the infertility group were significantly higher than those in the normal group. The incidence proportions of high-risk HPV types in the infertility group were significantly higher than those in the normal group, and the proportions of high-risk subtytes HPV16, HPV39, HV52, HPV56, and HPV68 were significantly higher in the infertility group than in the normal group. However, there were no significant differences in the incidences of low-risk HPV types. The incidence proportions of vaginal flora imbalance and HPV infection in the infertility group were significantly higher than those in the normal group. HPV16, HPV33, HPV51, HPV52and HPV58 infections were independent risk factors for infertility.

Conclusions
Vaginal microecological imbalance and HPV infection are directly related to infertility, and precautions should be taken.
Both T and B cells are indispensable for the development of a PBMC transfer-induced humanized mouse model for SSc
Authors: Shu Yaqing , Yue Xiaoyang , Wax Jacqueline , Kasper Brigitte , Yin Junping , Wang Xiaoqing , Zhang Liang , Ahmadi Marjan , Heidecke Harald , Müller Antje , Lamprecht Peter , Yu Xinhua , Riemekasten Gabriela , Petersen Frank 
Published: August 2022

Abstract
Background
Recently, a novel humanized mouse model for systemic sclerosis (SSc) was established by transferring peripheral blood mononuclear cells (PBMC) from patients with SSc to Rag2−/−Il2rg−/− immunodeficient mice. Here, we aimed to investigate the role of T and B cells in this humanized mouse model.

Methods
T and B cells were depleted in vitro from freshly isolated PBMC using anti-CD3 and anti-CD19 magnetic microbeads, respectively. Subsequently, PBMC and T or B cell-depleted PBMC were transferred into Rag2−/−/Il2rg−/− mice via intraperitoneal injection. Twelve weeks after the transfer, mice were sacrificed and evaluated.

Results
Mice transferred with whole PBMC from SSc patients developed systemic inflammation in the lungs, kidneys, and liver, and 6 out of 11 mice died or had to be sacrificed during the experiment. By contrast, such inflammation and death were not observed in mice transferred with corresponding T or B cell-depleted PBMC. In line with this finding, transfer with whole PBMC restored the splenic white pulp composing of human T, B, and plasma cells and led to the production of a considerable amount of human autoantibodies in recipient mice, while those immunological features were rarely observed in mice that received T or B cell-depleted PBMC. In contrast to our previous findings demonstrating a transfer of the protective effect of a B cell therapy into the mouse, treatment of SSc patients with chemical immunosuppressive drugs did not affect the pathogenicity of PBMC.

Conclusions
This study demonstrates that both T and B cells are indispensable for the pathogenesis of the PBMC transfer-induced mouse model for SSc.
Inhaled corticosteroids do not affect the antibody titer against the SARS-CoV-2 spike protein in BNT162b2 mRNA vaccinated patients
Authors: Nakajima Takeo , Nagano Tatsuya , Miyata Yoshiharu , Murakami Shoko , Mitsuyuki Satoshi , Funakoshi Yohei , Yakushijin Kimikazu , Horimoto Hitoshi , Nishimura Yoshihiro , Kobayashi Kazuyuki 
Published: August 2022

Abstract
Objectives
Oral corticosteroids reduce the antibody titer of the BNT162b2 mRNA vaccine against SARS-CoV-2. To date, the effect of inhaled corticosteroids on antibody titers is unknown.

Study design
The design of this study is retrospective study.

Methods
We analyzed the relationship between the clinical features and total antibody titers against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein in 320 subjects who had never been infected with Coronavirus disease 2019 (COVID-19) and were vaccinated the second time with the BNT162b2 mRNA vaccine between October 1 to December 28, 2021.

Results
Of the 320 subjects, 205 were treated with inhaled corticosteroids. The median antibody titer of patients treated with inhaled corticosteroids was 572 U/mL, which was significantly higher than that of patients treated without inhaled corticosteroids (454U/mL, P = 0.00258). The median antibody titers of smokers, men, and patients aged 65 years and over, were 315.5 U/mL, 385 U/mL, and 425.5 U/mL, respectively. These results are significantly lower than those of patients who never smoked, women, and patients aged less than 64 years (582 U/mL [P < 0.0001], 682.5 U/mL [P < 0.0001], and 717 U/mL [P < 0.0001], respectively). The multivariate analysis revealed that females and age were independent antibody titer-reducing factors (P = 0.0001 and P < 0.0001, respectively).

Conclusions
The use of inhaled corticosteroids did not reduce the antibody titer against SARS-CoV-2 spike protein. Clinicians should continue treatment with inhaled corticosteroids if indicated.
Orally administered Odoribacter laneus improves glucose control and inflammatory profile in obese mice by depleting circulating succinate
Authors: Huber-Ruano Isabel , Calvo Enrique , Mayneris-Perxachs Jordi , Rodríguez-Peña M-Mar , Ceperuelo-Mallafré Victòria , Cedó Lídia , Núñez-Roa Catalina , Miro-Blanch Joan , Arnoriaga-Rodríguez María , Balvay Aurélie , Maudet Claire , García-Roves Pablo , Yanes Oscar , Rabot Sylvie , Grimaud Ghjuvan Micaelu , De Prisco Annachiara , Amoruso Angela , Fernández-Real José Manuel , Vendrell Joan , Fernández-Veledo Sonia 
Published: August 2022

Abstract
Background
Succinate is produced by both human cells and by gut bacteria and couples metabolism to inflammation as an extracellular signaling transducer. Circulating succinate is elevated in patients with obesity and type 2 diabetes and is linked to numerous complications, yet no studies have specifically addressed the contribution of gut microbiota to systemic succinate or explored the consequences of reducing intestinal succinate levels in this setting.

Results
Using germ-free and microbiota-depleted mouse models, we show that the gut microbiota is a significant source of circulating succinate, which is elevated in obesity. We also show in vivo that therapeutic treatments with selected bacteria diminish the levels of circulating succinate in obese mice. Specifically, we demonstrate that Odoribacter laneus is a promising probiotic based on its ability to deplete succinate and improve glucose tolerance and the inflammatory profile in two independent models of obesity (db/db mice and diet-induced obese mice). Mechanistically, this is partly mediated by the succinate receptor 1. Supporting these preclinical findings, we demonstrate an inverse correlation between plasma and fecal levels of succinate in a cohort of patients with severe obesity. We also show that plasma succinate, which is associated with several components of metabolic syndrome including waist circumference, triglycerides, and uric acid, among others, is a primary determinant of insulin sensitivity evaluated by the euglycemic-hyperinsulinemic clamp.

Conclusions
Overall, our work uncovers O. laneus as a promising next-generation probiotic to deplete succinate and improve glucose tolerance and obesity-related inflammation.
Operational and investment efficiency of investment trust companies: Do foreign firms outperform domestic firms?
Authors: Nourani Mohammad , Kweh Qian Long , Lu Wen-Min , Gurrib Ikhlaas 
Published: August 2022

AbstractThis study examines the efficiency of investment trust companies (ITCs) from 2011 to 2020 using a meta-frontier two-stage network data envelopment analysis (DEA) based on the directional distance function (DDF). We improved the accuracy of the efficiency measurement and added a network-based ranking component to rank the top-performing entities. In the group-specific technology assessment, foreign ITCs excel in investment efficiency. Meanwhile, in the meta-technology assessment, domestic ITCs outperform foreign ITCs in terms of both investment and operational efficiencies. Group-specific technology efficiency scores were found to be lower than or equal to the meta-technology efficiency scores for both the operational and investment stages. Based on the network-based ranking approach, Yuan Ta, a domestic ITC that ranked fourth in the operational stage and first in the investment stage, can be used as a reliable benchmark. This study will enable practitioners to gain a better understanding of the performance of ITCs operating under heterogeneous technologies.
Pituitary stalk interruption syndrome (PSIS): do not miss this diagnosis
Authors: Agha Mahmoud , Sallam Maha Sallam Mohammed , Abougabal Ahmed M. , Abdelgawad Mohamed Saied 
Published: August 2022

Abstract
Background
Pituitary stalk interruption syndrome (PSIS) is one of the rare endocrinal aetiologies of the abnormal short stature. This is a syndrome characterized by a specific tirade, an absent or hypoplastic anterior pituitary gland, thin or absent infundibulum, and ectopic posterior pituitary location. This type of pituitary dwarfism is usually presented in the first decade of life and may be first isolated with normal other pituitary hormones.

Results
Only 3 out of 117 dwarf patients (2.5%) were found to have pituitary stalk interruption syndrome.

Conclusion
Although of rare incidence, pituitary stalk interruption syndrome (PSIS) is an entity which leads to pituitary dwarfism and should be kept in mind while investigating a child with pituitary dwarfism and radiologists should be aware of its rarely encountered diagnostic MRI findings for early diagnosis and treatment.
Circulating Tumor DNA Identifies Diverse Landscape of Acquired Resistance to Anti–Epidermal Growth Factor Receptor Therapy in Metastatic Colorectal Cancer
Authors: Topham James T. , O'Callaghan Chris J. , Feilotter Harriet , Kennecke Hagen F. , Lee Young S. , Li Weimin , Banks Kimberly C. , Quinn Katie , Renouf Daniel J. , Jonker Derek J. , Tu Dongsheng , Chen Eric X. , Loree Jonathan M. 
Published: August 2022

PURPOSE Anti–epidermal growth factor receptor (EGFR) antibodies are effective treatments for metastatic colorectal cancer. Improved understanding of acquired resistance mechanisms may facilitate circulating tumor DNA (ctDNA) monitoring, anti-EGFR rechallenge, and combinatorial strategies to delay resistance. METHODS Patients with treatment-refractory metastatic colorectal cancer (n = 169) enrolled on the CO.26 trial had pre–anti-EGFR tissue whole-exome sequencing (WES) compared with baseline and week 8 ctDNA assessments with the GuardantOMNI assay. Acquired alterations were compared between patients with prior anti-EGFR therapy (n = 66) and those without. Anti-EGFR therapy occurred a median of 111 days before ctDNA assessment. RESULTS ctDNA identified 12 genes with increased mutation frequency after anti-EGFR therapy, including EGFR ( P = .0007), KRAS ( P = .0017), LRP1B ( P = .0046), ZNF217 ( P = .0086), MAP2K1 ( P = .018), PIK3CG ( P = .018), BRAF ( P = .048), and NRAS ( P = .048). Acquired mutations appeared as multiple concurrent subclonal alterations, with most showing decay over time. Significant increases in copy-gain frequency were noted in 29 genes after anti-EGFR exposure, with notable alterations including EGFR ( P < .0001), SMO ( P < .0001), BRAF ( P < .0001), MET ( P = .0002), FLT3 ( P = .0002), NOTCH4 ( P = .0006), ERBB2 ( P = .004), and FGFR1 ( P = .006). Copy gains appeared stable without decay 8 weeks later. There were 13 gene fusions noted among 11 patients, all but one of which was associated with prior anti-EGFR therapy. Polyclonal resistance was common with acquisition of ≥ 10 resistance related alterations noted in 21% of patients with previous anti-EGFR therapy compared with 5% in those without ( P = .010). Although tumor mutation burden (TMB) did not differ pretreatment ( P = .63), anti-EGFR exposure increased TMB ( P = .028), whereas lack of anti-EGFR exposure resulted in declining TMB ( P = .014). CONCLUSION Paired tissue and ctDNA sequencing identified multiple novel mutations, copy gains, and fusions associated with anti-EGFR therapy that frequently co-occur as subclonal alterations in the same patient.
Time Fisher information associated with fluctuations in quantum geometry
Authors: Wani Salman Sajad , Quach James Q. , Faizal Mir 
Published: August 2022

Abstract
As time is not an observable, we use Fisher information (FI) to address the problem of time. We demonstrate that although the Hamiltonian operator is the generator of time, the Hamiltonian constraint operator cannot observe the change that arises through the passage of time. This is because the Hamiltonian constraint does not contain time FI. As we also identify an alternative operator on the world-sheet which does contain time FI, we argue that the timelessness of quantum gravity occurs due to the use of an inappropriate operator. We propose that a criterion for a physically meaningful operator in any quantum gravitational process is that it should contain non-vanishing time FI. Although we explicitly derive these results on the world-sheet of bosonic strings, we argue that it holds for any quantum geometry associated with time-reparametrization–invariant classical geometry.
Understanding How Pregnancy Protects Against Ovarian and Endometrial Cancer Development: Fetal Antigens May Be Involved
Authors: Main Claudia , Chen Xinyue , Zhao Min , Chamley Lawrence W , Chen Qi 
Published: August 2022

AbstractIt is well known that many factors, including infertility, obesity, type 2 diabetes, and family history of cancer, increase the risk of developing endometrial and ovarian cancer. However, multiparous women are known to have a lower risk of developing either ovarian or endometrial cancer than nonparous women. The lack of ovulation and shifting of sex hormonal balance, with decreased estrogen levels and increased progesterone levels during pregnancy, has traditionally been thought to be the major contributor to this decreased risk. However, in reality, the mechanisms underlying this phenomenon are relatively unknown. Increasing evidence suggests that endocrine factors are unlikely to completely explain the protective effect of pregnancies, and that multiple other nonendocrine mechanisms including fetal antigens and the newly proposed dormant cells hypothesis may also be involved. In this review, we summarize recent evidence and describe the potential underlying mechanisms that may explain how pregnancy protects against the development of ovarian and endometrial cancers in women's later life.
Value of radiomics based on CE-MRI for predicting the efficacy of neoadjuvant chemotherapy in invasive breast cancer
Authors: Li Qin , Huang Yan , Xiao Qin , Duan Shaofeng , Wang Simin , Li Jianwei , Niu Qingliang , Gu Yajia 
Published: August 2022

Objective: To establish and validate a radiomics nomogram based on contrast-enhanced (CE)-MRI for predicting the efficacy of neoadjuvant chemotherapy (NAC) in human epidermal growth factor receptor 2 (HER2)-positive breast cancer with non-mass enhancement (NME). Methods: A cohort comprising 117 HER2-positive breast cancer patients showing NME on CE-MRI between January 2012 and December 2019 were retrospectively analysed in our study. Patients were classified as pathological complete respone (pCR) according to surgical specimens and axillary lymph nodes without invasive tumour cells. Clinicopathological data were recorded, and images were assessed by two radiologists. A total of 1130 radiomics features were extracted from the primary tumour and six radiomics features were selected by the maximal relevance and minimal redundancy and least absolute shrinkage and selection operator algorithms. Univariate logistic regression was used to screen meaningful clinical and imaging features. The rad-score and independent risk factors were incorporated to build a nomogram model. Calibration and receiver operator characteristic curves were used to confirm the performance of the nomogram in the training and testing cohorts. The clinical usefulness of the nomogram was evaluated by decision curve analysis. Results: The difference in the rad-score between the pCR and non-pCR groups was significant in the training and testing cohorts (p < 0.01). The nomogram model showed good calibration and discrimination, with AUCs of 0.900 and 0.810 in the training and testing cohorts. Decision curve analysis indicated that the radiomics-based model was superior in terms of patient clinical benefit. Conclusion: The MRI-based radiomics nomogram model could be used to pre-operatively predict the efficacy of NAC in HER2-positive breast cancer patients showing NME. Advances in knowledge: HER2-positive breast cancer showing segmental enhancement on CE-MRI was more likely to achieve pCR after NAC than regional enhancement and diffuse enhancement. The MRI-based radiomics nomogram model could be used to pre-operatively predict the efficacy of NAC in HER2-positive breast cancer that showed NME.
Monkeypox - review
Authors: Kuchnicka Aleksandra Amalia , Kosz Katarzyna , Kuchnicka Julia , Remjasz Klaudia , Zarankiewicz Natalia , Zielińska Martyna , Sapuła Klaudia , Aleksandrowicz Jakub , Siedlecki Wojciech 
Published: August 2022

Introduction and purpose:
This review aims to analyze the current information about monkeypox and the virus which causes the disease.
Material and method:
This review was based on articles collected in PubMed and published in the years 2012-2022
The research was done by looking through keywords as follows: „monkeypox”; „zoonosis”;„tecovirimat”
Results:
The selected studies have demonstrated that the monkeypox virus is a high-danger pathogen that causes a disease important to public health. More research on this topic has to be done to prevent and better comprehend the potential threat.
Conclusions:
According to the cited research, public health systems should be aware of practical methods to reduce the risk of monkeypox spreading. It is crucial to monitor the spreading of the monkeypox disease and create effective preparation. Moreover, governments should develop strategies to prevent their population.
The potential of cannabinoids in the treatment of lung cancer
Authors: Drozd Małgorzata , Marzęda Paweł , Czarnota Jakub , Dobrzyński Michał , Skubel Tomasz , Dudek Iga , Rybak Natalia 
Published: August 2022

Introduction: Lung cancer is the number-one cause of death due to neoplasms worldwide. The 5-year overall survival rate is only 22%. In advanced stages, the therapeutic options are limited to chemotherapy, radiotherapy, molecularly targeted therapy and immunotherapy. Phytocannabinoids, the components of Cannabis sativa, their synthetic derivatives and endogenous cannabinoids have demonstrated anticancer activity in various common cancers - breast, prostate, colorectal and lung cancers, among others. The aim of this review was to assess the potential value of cannabinoids in the treatment of lung cancer.
State of knowledge: The majority of preclinical studies demonstrates that cannabinoids inhibit lung cancer cell viability both in vitro and in vivo. The main mechanism of anticancer activity is the induction of apoptosis, triggered by activation of CB1, CB2 and TRPV1 receptors or independently via other pathways. Cannabinoids influence the components of the tumour microenvironment - cancer associated fibroblasts, macrophages and lymphokine-activated-killer cells. Cannabinoids alter leukocyte infiltration into anti-cancer proportions, inhibit expression of EGFR and PAI-1 and increase the expression of TIMP-1. As a result they induce cytotoxicity, decrease proliferation, migration and invasive potential of lung cancer cells, suppress angiogenesis and metastasis forming. Patients with advanced lung cancer may also benefit from analgesic, antiemetic and appetite improving properties of cannabinoids.
Summary: Cannabinoids can be a supplementary agent in systemic anticancer therapeutic regimen in the future. The exact mechanisms of action, specific doses in anticancer treatment, routes of administration and interactions with other anticancer drugs has yet to be determined. Thus the clinical studies on cannabinoids in lung cancer should be performed in the future.