bluuebunny/crossref_metadata_2025_split huggingface dataset:
Suggestive evidence of the genetic association of TMOD1 and PTCSC2 polymorphisms with thyroid carcinoma in the Chinese Han population
Authors: Tong Kaijun , Zhang Chang , Yang Tingting , Guo Rongbiao , Wang Xinyuan , Guan Renyang , Jin Tianbo 
Published: October 2022

Abstract
Background
The purpose of this study was to survey the associations of six single nucleotide polymorphisms (SNPs) in the TMOD1 and PTCSC2 genes with thyroid carcinoma (TC).

Method
Peripheral blood samples were obtained from 510 patients with TC and 509 normal controls. Six SNPs were genotyped by the Agena MassARRAY platform. Logistic regression was used to evaluate the association between SNPs and TC susceptibility by calculating odds ratios (ORs) and 95% confidence intervals (CIs). SNP-SNP interactions were analyzed by multifactor dimensionality reduction (MDR).

Results
Our study showed that rs925489 (OR = 1.45, p = 0.011) and rs965513 (OR = 1.40, p = 0.021) were significantly associated with an increased risk of TC. Rs10982622 decreased TC risk (OR = 0.74, p = 0.025). Further stratification analysis showed that rs10982622 reduced the susceptibility to TC in patients aged ≤ 45 years (OR = 0.69, p = 0.019) and in females (OR = 0.61, p = 0.014). Rs925489 increased TC risk in people aged > 45 years (OR = 1.54, p = 0.044) and in males (OR = 2.34, p = 0.003). In addition, rs965513 was related to an increased risk of TC in males (OR = 2.14, p = 0.007). Additionally, haplotypes in the block (rs925489|rs965513) significantly increased TC risk (p < 0.05). The best predictive model for TC was the combination of rs1052270, rs10982622, rs1475545, rs16924016, and rs925489.

Conclusion
TMOD1 and PTCSC2 polymorphisms were separately correlated with a remarkable decrease and increase in TC risk based on the analysis.
Interpretable machine learning predicts cardiac resynchronization therapy responses from personalized biochemical and biomechanical features
Authors: Haque Anamul , Stubbs Doug , Hubig Nina C. , Spinale Francis G. , Richardson William J. 
Published: October 2022

Abstract
Background
Cardiac Resynchronization Therapy (CRT) is a widely used, device-based therapy for patients with left ventricle (LV) failure. Unfortunately, many patients do not benefit from CRT, so there is potential value in identifying this group of non-responders before CRT implementation. Past studies suggest that predicting CRT response will require diverse variables, including demographic, biomarker, and LV function data. Accordingly, the objective of this study was to integrate diverse variable types into a machine learning algorithm for predicting individual patient responses to CRT.

Methods
We built an ensemble classification algorithm using previously acquired data from the SMART-AV CRT clinical trial (n = 794 patients). We used five-fold stratified cross-validation on 80% of the patients (n = 635) to train the model with variables collected at 0 months (before initiating CRT), and the remaining 20% of the patients (n = 159) were used as a hold-out test set for model validation. To improve model interpretability, we quantified feature importance values using SHapley Additive exPlanations (SHAP) analysis and used Local Interpretable Model-agnostic Explanations (LIME) to explain patient-specific predictions.

Results
Our classification algorithm incorporated 26 patient demographic and medical history variables, 12 biomarker variables, and 18 LV functional variables, which yielded correct prediction of CRT response in 71% of patients. Additional patient stratification to identify the subgroups with the highest or lowest likelihood of response showed 96% accuracy with 22 correct predictions out of 23 patients in the highest and lowest responder groups.

Conclusion
Computationally integrating general patient characteristics, comorbidities, therapy history, circulating biomarkers, and LV function data available before CRT intervention can improve the prediction of individual patient responses.
SIRPα antibody combined with oncolytic virus OH2 protects against tumours by activating innate immunity and reprogramming the tumour immune microenvironment
Authors: Kong Defeng , Yang Zhenrong , Li Guoliang , Wu Quanyou , Gu Zhaoru , Wan Duo , Zhang Qi , Zhang Xiaoli , Cheng Shujun , Liu Binlei , Zhang Kaitai , Zhang Wen 
Published: October 2022

Abstract
Background
The combination of oncolytic viruses (OVs) with immune checkpoint blockades is a research hotspot and has shown good efficacy. Here, we present the first attempt to combine oncolytic herpes simplex virus 2 (OH2) with an anti-SIRPα antibody as an antitumour treatment. Our results provide unique insight into the combination of innate immunity with OV.

Methods
We verified the polarization and activation of OH2 in RAW264.7 cells in vitro. Subsequently, we evaluated the antitumour ability of OH2 and anti-SIRPα combined therapy in a tumour-bearing mouse model. RNA-seq and Single-cell RNA-seq were used to characterize the changes in the tumour microenvironment.

Results
The OH2 lysates effectively stimulated RAW264.7 cells to polarize towards the M1 but not the M2 phenotype and activated the function of the M1 phenotype in vitro. In the macrophage clearance experiment, OH2 therapy induced polarization of M1 macrophages and participated in the antitumour immune response in a tumour-bearing mouse model. Treatment with a combination of OH2 and anti-SIRPα effectively inhibited tumour growth and significantly prolonged the survival time of the mice, and this result was more obvious in the mouse model with a larger tumour volume at the beginning of the treatment. These results suggest that combination therapy can more profoundly reshape the TME and activate stronger innate and adaptive immune responses.

Conclusions
Our data support the feasibility of oncolytic virus therapy in combination with anti-SIRPα antibodies and suggest a new strategy for oncolytic virus therapy.
Pigmentary mosaicism as a recurrent clinical manifestation in three new patients with mosaic trisomy 12 diagnosed postnatally: cases report and literature review
Authors: Martínez-Hernández A. , Martínez-Anaya D. , Durán-McKinster C. , Del Castillo-Ruiz V. , Navarrete-Meneses P. , Córdova E. J. , Villegas-Torres B. E. , Ruiz-Herrera A. , Juárez-Velázquez R. , Yokoyama-Rebollar E. , Cervantes-Barragán D. , Pedraza-Meléndez A. , Orozco L. , Pérez-Vera P. , Salas-Labadía C. 
Published: October 2022

Abstract
Background
To date, only twenty-one cases diagnosed postnatally with mosaic trisomy 12 have been reported. The most frequent phenotypic manifestations are developmental delay, dysmorphic facial features, congenital heart defects, digital alterations, and pigmentary disorders. In the present report, detailed clinical and genetic profiles of three unrelated new patients with mosaic trisomy 12 are described and compared with previously reported cases.

Case presentation
In the present report, we include the clinical, cytogenetic, and molecular description of three Mexican patients diagnosed postnatally with mosaic trisomy 12. At phenotypic level, the three patients present with developmental delay, dysmorphic facial features, congenital heart defects and skin pigmentary anomalies. Particularly, patient 1 showed unique eye alterations as bilateral distichiasis, triple rows of upper lashes, and digital abnormalities. In patient 2 redundant skin, severe hearing loss, and hypotonia were observed, and patient 3 presented with hypertelorism and telecanthus. Hyperpigmentation with disseminated pigmentary anomalies is a common trait in all of them. The cytogenetic study was carried out under the strict criteria of analysis, screening 50–100 metaphases from three different tissues, showing trisomy 12 mosaicism in at least one of the three different tissues analyzed. With SNParray, the presence of low-level mosaic copy number variants not previously detected by cytogenetics, and uniparental disomy of chromosome 12, was excluded. STR markers allowed to confirm the absence of uniparental disomy as well as to know the parental origin of supernumerary chromosome 12.

Conclusions
The detailed clinical, cytogenetic, and molecular description of these three new patients, contributes with relevant information to delineate more accurately a group of patients that show a heterogeneous phenotype, although sharing the same chromosomal alteration. The possibility of detecting mosaic trisomy 12 is directly associated with the sensitivity of the methodology applied to reveal the low-level chromosomal mosaicism, as well as with the possibility to perform the analysis in a suitable tissue.
Outcome of autologous stem cell transplantation in patients with favorable-risk acute myeloid leukemia in first remission
Authors: Chen Juan , Liu Li , Ma Runzhi , Pang Aiming , Yang Donglin , Chen Xin , Wei Jialin , He Yi , Zhang Rongli , Zhai Weihua , Ma Qiaoling , Jiang Erlie , Han Mingzhe , Zhou Jiaxi , Feng Sizhou 
Published: October 2022

Abstract
Objective
To evaluate the efficacy of autologous hematopoietic stem cell transplantation (auto-HSCT) in patients with favorable-risk acute myeloid leukemia in first remission.

Method
Twenty patients who received auto-HSCT at our center between January 2014 and January 2021 were retrospectively reviewed.

Results
Until last follow-up, three patients in the cohort were dead due to relapse. The estimated 1-year and 5-year overall survival were 95.00% ± 4.87% and 83.82% ± 8.58%, respectively. The estimated 5-year RFS and CIR (cumulative incidence of relapse) were 85.00% ± 7.98% and 15.00% ±7.98%, respectively.

Conclusion
The outcome of auto-HSCT in patients with favorable-risk acute myeloid leukemia in first remission was excellent and auto-HSCT could be an effective treatment for these patients.
Bone-targeting delivery of platelet lysate exosomes ameliorates glucocorticoid-induced osteoporosis by enhancing bone-vessel coupling
Authors: Zheng Gang , Ma Hai-Wei , Xiang Guang-Heng , He Gao-Lu , Cai Han-Chen , Dai Zi-Han , Chen Yan-Lin , Lin Yan , Xu Hua-Zi , Ni Wen-Fei , Xu Cong , Liu Hai-Xiao , Wang Xiang-Yang 
Published: October 2022

AbstractBackgroundGlucocorticoids (GCs) overuse is associated with decreased bone mass and osseous vasculature destruction, leading to severe osteoporosis. Platelet lysates (PL) as a pool of growth factors (GFs) were widely used in local bone repair by its potent pro-regeneration and pro-angiogenesis. However, it is still seldom applied for treating systemic osteopathia due to the lack of a suitable delivery strategy. The non-targeted distribution of GFs might cause tumorigenesis in other organs.ResultsIn this study, PL-derived exosomes (PL-exo) were isolated to enrich the platelet-derived GFs, followed by conjugating with alendronate (ALN) grafted PEGylated phospholipid (DSPE-PEG-ALN) to establish a bone-targeting PL-exo (PL-exo-ALN). The in vitro hydroxyapatite binding affinity and in vivo bone targeting aggregation of PL-exo were significantly enhanced after ALN modification. Besides directly modulating the osteogenic and angiogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and endothelial progenitor cells (EPCs), respectively, PL-exo-ALN also facilitate their coupling under GCs’ stimulation. Additionally, intravenous injection of PL-exo-ALN could successfully rescue GCs induced osteoporosis (GIOP) in vivo.ConclusionsPL-exo-ALN may be utilized as a novel nanoplatform for precise infusion of GFs to bone sites and exerts promising therapeutic potential for GIOP.Graphical Abstract
Efficacy and safety of oral anticoagulants in elderly patients with stable coronary artery disease and atrial fibrillation
Authors: Zhang Xu , Wu Yangxun , Lv Chao , Zhang Shizhao , Liu Haiping , Wang Yuyan , Zou Yuting , Qin Liu’an , Zhang Junmeng , Yin Tong 
Published: October 2022

AbstractBackgroundThis study aimed to evaluate the efficacy and safety of oral anticoagulants (OACs) in real-world elderly patients with comorbidities of stable coronary artery disease (SCAD) and atrial fibrillation (AF).MethodsElderly patients (aged ≥ 65 years old) diagnosed with SCAD and AF were consecutively recruited and grouped into patients with or without oral anticoagulant (OAC) treatment. Follow-up was performed for 5 years. Major adverse cardiac events (MACEs) were defined as a composite of all-cause death, nonfatal myocardial infarction (MI), nonfatal stroke, and systemic embolism. Major bleeding outcomes were defined as events that were type ≥ 3 based on the Bleeding Academic Research Consortium (BARC) criteria. The net clinical outcomes were defined as the combination of MACEs and bleeding of BARC type ≥ 3.ResultsA cohort of 832 eligible patients (78 ± 6.70 years) was included. Compared to the patients without OAC treatment (n = 531, 63.82%), the patients treated with OAC (n = 301, 36.18%) were much younger, had higher body mass index (BMI), and had lower prevalence of heart failure, chronic obstructive pulmonary disease (COPD), renal insufficiency, and previous myocardial infarction. During the follow-up of 5 years, compared to the patients without OAC treatment, patients with OAC had a significantly lower risk of MACEs (20.60% vs. 58.95%, adjusted HR: 0.21, 95% CI: 0.15–0.30,p < 0.001) but a higher risk of BARC ≥ 3 bleeding events (4.65% vs. 1.32%, adjusted HR: 4.71, 95% CI: 1.75–12.64,p = 0.002). In combination, a lower risk of net clinical outcomes could be observed in the patients with OACs (23.26% vs. 58.96%, adjusted HR: 0.27, 95% CI: 0.19–0.38,p < 0.001). Among the patients with OAC treatment, no significant difference was found for MACEs or BARC ≥ 3 bleeding events between the patients with or without comedications of oral antiplatelet agents.ConclusionsA net clinical benefit of efficacy and safety could be observed in OAC-treated elderly patients with SCAD and AF. This benefit is independent of the comedications of oral antiplatelet treatment.
A research intelligence approach to assess the research impact of the Dutch university medical centres
Authors: Iping Rik , Kroon Marielle , Steegers Chantal , van Leeuwen Thed 
Published: October 2022

Abstract
Background
The way in which research impact is evaluated and assessed has long been under debate. In recent years the focus is moving away from the use of numerical indicators, towards an emphasis on narratives. The Dutch university medical centres (UMCs) have a long-standing tradition of using bibliometric indicators. Because of the declining interest in indicators alone, this study was designed to repurpose bibliometrics to answer specific strategic questions. In this article we discuss the strategic and policy-based questions, the methodology we used in uncovering relevant information and conclusions we draw from the analyses we performed. The aim of this article is to inform a broader audience about the potential applications of bibliometric information to support a new form of research intelligence.

Methods
In this study we used a curated set of publications from the UMCs. We performed different bibliometric analyses and used bibliometric visualization tools to shed light on research focus, open science practices, collaboration, societal impact and scientific impact.

Results
The analyses allowed us to visualize and contextualize the research focus of the UMCs as a whole, but also to show specific focus areas of each UMC. The UMCs are active in the full spectrum of biomedical research, and at the same time are very complementary to each other. Furthermore, we were able to show the development of open access of UMC publications over time, to support the national mission. Visualizing collaboration is a powerful way of showing both the international orientation and the regional and national engine function of UMCs in research. We were able to assess societal impact by looking at the different channels in which publications find their way to societally relevant sources such as news media, policy documents and guidelines. Finally, we assessed scientific impact and put this into an international perspective.

Conclusions
Research intelligence is able to transform bibliometric information by interpretation and annotation into highly relevant insights that can be used for several different strategic purposes and for research impact assessment in general.
Potential role of autophagy induced by FLT3-ITD and acid ceramidase in acute myeloid leukemia chemo-resistance: new insights
Authors: Zalpoor Hamidreza , Bakhtiyari Maryam , Akbari Abdullatif , Aziziyan Fatemeh , Shapourian Hooriyeh , Liaghat Mahsa , Zare-Badie Zahra , Yahyazadeh Sheida , Tarhriz Vahideh , Ganjalikhani-Hakemi Mazdak 
Published: October 2022

AbstractAcute myeloid leukemia (AML) is a type of leukemia with a poor prognosis and survival characterized by abnormal cell proliferation and differentiation. Despite advances in treatment, AML still has a low complete remission rate, particularly in elderly patients, and recurrences are frequently seen even after complete remissions. The major challenge in treating AML is the resistance of leukemia cells to chemotherapy drugs. Thus, to overcome this issue, it can be crucial to conduct new investigations to explore the mechanisms of chemo-resistance in AML and target them. In this review, the potential role of autophagy induced by FLT3-ITD and acid ceramidase in chemo-resistance in AML patients are analyzed. With regard to the high prevalence of FLT3-ITD mutation (about 25% of AML cases) and high level of acid ceramidase in these patients, we hypothesized that both of these factors could lead to chemo-resistance by inducing autophagy. Therefore, pharmacological targeting of autophagy, FLT3-ITD, and acid ceramidase production could be a promising therapeutic approach for such AML patients to overcome chemo-resistance.
Human adenoviral (HAdV) chronic arthritis expands the infectious spectrum of primary agammaglobulinemia
Authors: de Frémont Grégoire Martin , Salmona Maud , Maillet François , Garzaro Margaux , Bertinchamp Rémi , Simonnet Arthur , Feghoul Linda , Maki Guitta , Roelens Marie , Chotard Emilie , Picard Capucine , Oksenhendler Eric , LeGoff Jérôme , Boutboul David 
Published: October 2022

AbstractInborn errors of immunity (IEI) are a heterogeneous entity with an increasing number of late diagnoses. Besides infections, inflammatory manifestations are a growing part of the clinical landscape of IEI. These complications are of unknown causes and often lead to the prescription of immunosuppressive agents that worsen the underlying immune defect. We here report the case of an adult patient diagnosed with chronic Human Adenovirus C-1 arthritis in the setting of primary agammaglobulinemia. Metagenomic next-generation sequencing led to the correct diagnosis and high-dose intravenous immunoglobulins resulted in complete recovery. This observation gives new insights into adenoviral immunity and underlines the importance of metagenomics in the diagnosis of inflammatory manifestations in immunocompromised patients.
Analysis of different adipose depot gene expression in cachectic patients with gastric cancer
Authors: Han Jun , Ding Zuoyou , Zhuang Qiulin , Shen Lei , Yang Fan , Sah Szechun , Wu Guohao 
Published: October 2022

Abstract
Purpose
This study aimed to identify the differentially expressed genes (DEGs) that contributed to the different amount of fat loss between subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) among cachectic patients.

Methods
RNA sequencing was performed and bioinformatic tools were utilized to analyze the biological functions and construct regulation networks of DEGs. We presumed that iroquois homeobox 1 (IRX1) to be a hub gene and analyzed its clinical significance. Mouse model of cancer cachexia was established and differences between SAT and VAT were compared. The function of IRX1 on lipid metabolism was clarified by Oil Red O staining, qRT-PCR, and Western blotting in adipocytes.

Results
A total of 455 DEGs were screened between SAT and VAT in cachectic patients. Several hub genes were selected and IRX1 was presumed to contribute to the pathological difference between SAT and VAT in cancer cachexia. Patients with higher expression of IRX1 in SAT than VAT revealed significantly higher weight loss, IL-6 and TNF-α, as well as lower BMI, SAT, and VAT area. IRX1 expression in SAT was negatively correlated with SAT area. In cachectic mice, the expression of IRX1 in SAT was significantly higher than that in VAT. The inhibition effect on adipogenesis exerted by IRX1 was also proved in vitro.

Conclusion
These data supported that DEGs contribute to the different degrees of fat loss among adipose depots in cachectic patients. IRX1 in SAT promoted fat loss by inhibiting adipocyte differentiation and adipogenesis.
Folliculin-interacting protein FNIP2 impacts on overweight and obesity through a polymorphism in a conserved 3′ untranslated region
Authors: Fernández Lara P. , Deleyto-Seldas Nerea , Colmenarejo Gonzalo , Sanz Alba , Wagner Sonia , Plata-Gómez Ana Belén , Gómez-Patiño Mónica , Molina Susana , Espinosa-Salinas Isabel , Aguilar-Aguilar Elena , Ortega Sagrario , Graña-Castro Osvaldo , Loria-Kohen Viviana , Fernández-Marcos Pablo J. , Efeyan Alejo , Ramírez de Molina Ana 
Published: October 2022

AbstractBackgroundOverweight and obesity are defined by an anomalous or excessive fat accumulation that may compromise health. To find single-nucleotide polymorphisms (SNPs) influencing metabolic phenotypes associated with the obesity state, we analyze multiple anthropometric and clinical parameters in a cohort of 790 healthy volunteers and study potential associations with 48 manually curated SNPs, in metabolic genes functionally associated with the mechanistic target of rapamycin (mTOR) pathway.ResultsWe identify and validate rs2291007 within a conserved region in the 3′UTR of folliculin-interacting protein FNIP2 that correlates with multiple leanness parameters. The T-to-C variant represents the major allele in Europeans and disrupts an ancestral target sequence of the miRNA miR-181b-5p, thus resulting in increasedFNIP2mRNA levels in cancer cell lines and in peripheral blood from carriers of the C allele. Because the miRNA binding site is conserved across vertebrates, we engineered the T-to-C substitution in the endogenousFnip2allele in mice. Primary cells derived fromFnip2C/C mice show increased mRNA stability, and more importantly,Fnip2C/C mice replicate the decreased adiposity and increased leanness observed in human volunteers. Finally, expression levels ofFNIP2in both human samples and mice negatively associate with leanness parameters, and moreover, are the most important contributor in a multifactorial model of body mass index prediction.ConclusionsWe propose that rs2291007 influences human leanness through an evolutionarily conserved modulation ofFNIP2mRNA levels.Graphical Abstract