bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phosphorylation of PPDPF via IL6‐JAK2 activates the Wnt/β‐catenin pathway in colorectal cancer
Authors: Zi Yuyuan , Liu Liyu , Gao Jie , Xu Xu , Guan Yidi , Rong Zhuoxian , Cao Zhen , Li Mengwei , Zeng Zimei , Fan Qi , Tang Feiyu , He Junju , Feng Dan , Chen Jionghuang , Dai Yuedi , Huang Yufeng , Nie Yingjie , Pei Haiping , Cai Qingping , Li Zhi , Sun Lunquan , Deng Yuezhen 
Published: July 2023

AbstractInflammation plays an important role in the initiation and progression of colorectal cancer (CRC) and leads to β‐catenin accumulation in colitis‐related CRC. However, the mechanism remains largely unknown. Here, pancreatic progenitor cell differentiation and proliferation factor (PPDPF) is found to be upregulated in CRC and significantly correlated with tumor‐node‐metastasis (TNM) stages and survival time. Knockout of PPDPF in the intestinal epithelium shortens crypts, decreases the number of stem cells, and inhibits the growth of organoids and the occurrence of azoxymethane (AOM)/dextran sodium sulfate (DSS)‐induced CRC. Mechanistically, PPDPF is found to interact with Casein kinase 1α (CK1α), thereby disrupting its binding to Axin, disassociating the β‐catenin destruction complex, decreasing the phosphorylation of β‐catenin, and activating the Wnt/β‐catenin pathway. Furthermore, interleukin 6 (IL6)/Janus kinase 2 (JAK2)‐mediated inflammatory signals lead to phosphorylation of PPDPF at Tyr16 and Tyr17, stabilizing the protein. In summary, this study demonstrates that PPDPF is a key molecule in CRC carcinogenesis and progression that connects inflammatory signals to the Wnt/β‐catenin signaling pathway, providing a potential novel therapeutic target.
The SIR epidemic model with diffusion and nonlinear incidence: a symmetry approach
Authors: Naz R , Johnpillai A , Mahomed F , Omamed A. 
Published: July 2023

Abstract

We use Lie point symmetries to obtain reductions and closed-form solutions for the
diffusive SIR epidemic model with diffusion and nonlinear incidence. We determine
that the Lie algebra for this model is three-dimensional. We invoke these to establish
closed-form solutions of the diffusive SIR model. Furthermore, we utilized the closedform
solutions to generate a graphical representation of the infected curve, and
carried out a sensitivity analysis to gain valuable insights into the transmission
dynamics of the epidemic. Additionally, the most general Lie symmetry generator
is used to find the reductions and numerical solutions.
Lidocaine could promote the cuproptosis through up-regulating the long noncoding RNA DNMBP-AS1 in laryngeal cancer
Authors: Yu Yi , He Yi , Lv Meihong 
Published: July 2023

AbstractBackground:Lidocaine is a traditional local anesthetic, which has been reported to trigger apoptosis through the mitochondrial pathway, independent of death receptor signaling. Cuproptosis is a copper triggered mitochondrial cell death mode. In this study, we explored the biological effects of lidocaine on laryngeal cancer and studied the relevant mechanisms of cuproptosisMethods:quantitative RT-PCR weas used to measure the expression level of long noncoding RNA (IncRNA) DNMBP-AS1. DNMBP-AS1 siRNA (si-DNMBP-AS1) were transfected into Hep-2 cells to verify the roles of DNMBP-AS1 in cuproptosis. 24 hours treatment with 20 nM elesclomol and 2 µM CuCl2 was performed to promote the occurrence of Cuproptosis. Cell proliferation and apoptosis assays ware utilized to analyze biological effect of lidocaine on Hep-2 cells.Results:DNMBP-AS1 was significantly upregulated during cuproptosis in Hep-2 cells. The si-DNMBP-AS1 significantly increased the cell viability, and suppress the cuproptosis. Lidocaine was cytotoxic to the Hep-2 cells in a dose- and time-dependent manner. Exposure to 10 μM of lidocaine for 24 hours did not reduce the viability, but significantly increased the expression of DNMBP-AS1, and promote the cuproptosis. Anymore, si-DNMBP-AS1 reverse the pro-cuproptosis function of lidocaine.Conclusions:lidocaine was cytotoxic to human laryngeal cancer cells in a time- and dose-dependent manner, promoted the cuproptosis through up-regulating DNMBP-AS1. The results of this study offer initial optimism that lidocaine can be used in an adjuvant or neoadjuvant fashion in laryngeal cancer treatment.
Cross-Reactivity and sequence similarity between microbial transglutaminase and human antigens: expanded exposome of autoimmune diseases
Authors: Lerner Aaron , Benzvi Carina , Vojdani Aristo 
Published: July 2023

Abstract
Microbial transglutaminase (mTG) is a bacterial survival factor, frequently used as a food additive to glue processed nutrients. As a result, new immunogenic epitopes are generated that might drive autoimmunity. Presently, its contribution to autoimmunity through epitope similarity and cross-reactivity was investigated. Emboss Matcher was used to perform sequence alignment between mTG and various antigens implicated in many autoimmune diseases. Monoclonal and polyclonal antibodies made specifically against mTG were applied to 77 different human tissue antigens using ELISA. Six antigens were detected to share significant homology with mTG immunogenic sequences, representing major targets of common autoimmune conditions. Polyclonal antibody to mTG reacted significantly with 17 out of 77 tissue antigens. This reaction was most pronounced with mitochondrial M2, ANA, and extractable nuclear antigens. The results indicate that sequence similarity and cross-reactivity between mTG and various tissue antigens are possible, supporting the relationship between mTG and the development of autoimmune disorders. 150W
Genome-Wide Analysis of PIN Genes in Cultivated Peanuts (Arachis hypogaea L.): Identification, Subcellular location, Evolution, and Expression patterns
Authors: Bian Jianxin , Cui Yuanyuan , Li Jihua , Guan Yu , Tian Shuhua , Liu Xiaoqin 
Published: July 2023

Abstract
Background
Auxin is an important hormone in plants and the PIN-FORMED (PIN) genes are essential to auxin distribution in growth and developmental processes of plants. ​Peanut is an influential cash crop, but research into PIN genes in peanuts remains limited.​
Results
In this study, 27 PIN genes were identified in the genome of cultivated peanut, resolving into four subfamilies. Most of the PIN genes were predicted to be located in the plasma membrane and a subcellular location experiment confirmed the prediction. The gene structure, cis-elements in the promoter, and evolutionary relationships were elucidated, facilitating our understanding of peanut PINs and their evolution. In addition, the expression patterns of these PINs in various tissues were analyzed according to a previously published transcriptome dataset and qRT-PCR, which gave us a clear understanding of the temporal and spatial expression of PIN genes in different growth stages and different tissues. Expression during peanut pod development helps us to study geotropism of the peanut peg. Moreover, the gene network and gene ontology enrichment of these PINs were presented.
Conclusions
This study details a comprehensive analysis of PIN genes in cultivated peanuts and lays the foundation for subsequent studies of peanut gene function and phenotype.
Exploration of biomarkers for systemic lupus erythematosus by machine-learning analysis
Authors: Zhao Xingyun , Duan Lishuang , Cui Dawei , Xie Jue 
Published: July 2023

Abstract
Background
In recent years, research on the pathogenesis of systemic lupus erythematosus (SLE) has made great progress. However, the prognosis of the disease remains poor, and high sensitivity and accurate biomarkers are particularly important for the early diagnosis of SLE.
Methods
SLE patient information was acquired from three Gene Expression Omnibus (GEO) databases and used for differential gene expression analysis, such as weighted gene coexpression network (WGCNA) and functional enrichment analysis. Subsequently, three algorithms, random forest (RF), support vector machine-recursive feature elimination (SVM-REF) and least absolute shrinkage and selection operation (LASSO), were used to analyze the above key genes. Furthermore, the expression levels of the final core genes in peripheral blood from SLE patients were confirmed by real-time polymerase chain reaction (PCR) assay.
Results
Five core genes (ABCB1, CD247, DSC1, KIR2DL3 and MX2) were found in this study. Moreover, the nomogram model showed that the five optimal key genes had good reliability and validity, which were further confirmed by clinical samples from SLE patients. The receiver operating characteristic (ROC) curves of the five genes also revealed that they had critical roles in the pathogenesis of SLE.
Conclusion
Overall, five key genes were obtained and validated through machine-learning analysis of the databases, which might offer a new perspective for the molecular mechanism and potential therapeutic targets for SLE.
External validation of the VIGex gene-expression signature as a novel predictive biomarker for immune checkpoint treatment
Authors: Bedard Philippe , Hernando-Calvo Alberto , Yang Cindy , Vila-Casadesús Maria , Han Ming , Liu Amy , Berman Hal , Spreafico Anna , Razak Albiruni , Lheureux Stephanie , Hansen Aaron , Giacco Deborah Lo , Matito Judit , Pugh Trevor , Bratman Scott , Aleshin Alexey , Berche Roger , Saavedra Omar , Garralda Elena , Elston Sawako , Siu Lillian , Ohashi Pamela , Vivancos Ana 
Published: July 2023

Abstract
Immune gene expression signatures are emerging as potential biomarkers for immunotherapy. Yet, their limited predictive performance and complexity limit routine clinical implementation. VIGex is a 12-gene expression classifier developed in both nCounter (Nanostring) and RNA-Seq assays and analytically validated across laboratories. VIGex classifies tumor samples into Hot, Intermediate-Cold (I-Cold) and Cold subgroups. VIGex-Hot has been associated with better immunotherapy (IO) treatment outcomes. Here we investigated the performance of VIGex and other IO biomarkers in an independent dataset of patients treated with Pembrolizumab in the INSPIRE phase 2 clinical trial (NCT02644369). Patients with advanced solid tumors were treated with Pembrolizumab 200 mg IV every 3 weeks. Tumor RNA-seq data from baseline tumor samples were classified by the VIGex algorithm. Circulating tumor DNA (ctDNA) was measured at baseline and start of cycle 3 using the bespoke Signatera™ assay. VIGex-Hot was compared to VIGex Intermediate-Cold + Cold and 4 groups were defined based on the combination of VIGex subgroups and the change in ctDNA at cycle 3 from baseline (ΔctDNA). Seventy-six patients were enrolled including 16 ovarian, 12 breast, 12 head and neck cancers, 10 melanoma and 26 other tumor types. Objective response rate was 24% in VIGex-Hot and 10% in I-Cold/Cold. VIGex-Hot subgroup was associated with higher OS (HR: 0.43; p = 0.009) and PFS (HR: 0.49; p = 0.036) when included in a multivariable model adjusted for tumor type, tumor mutational burden (TMB) and PD-L1 immunohistochemistry. The addition of ΔctDNA improved the predictive performance of the baseline VIGex classification for both OS and PFS. Our data indicate that the addition of ΔctDNA to baseline VIGex may refine prediction for IO.
The medical school dean: Understanding the development of a leader through Self- Determination Theory
Authors: Alwazzan Lulu 
Published: July 2023

Abstract
How a dean develops in context is crucial for our understanding of medical school administration. Exploring deans’ leadership experience may enrich our understanding of how they emerge, enact, and remain in administration. This study explores essential components of individual development and learning as outlined by Self-Determination Theory; that is, how deans develop autonomy in leadership, competency to lead, and a sense of belonging to medical schools. Semi-structured interviews were conducted with medical school deans in Riyadh city, Saudi Arabia. Participants were invited via email. Informed consent was secured. Interviews were conducted virtually, audio-recorded and transcribed. Data were analyzed using framework analysis. Five participants took part in the study. Eight themes were identified and in direct relation to the research questions:1) Leader’s autonomy: Defining autonomy and role negotiation), 2) Leader’s competency in leadership: Experience of mastery, influence of resources, formal leadership programs, and achievement of organizational goals), and 3) Sense of belonging: Interpersonal relationships and personal fulfillment. This study provides insights on the development of leaders in medical education at the granular level. Investment in developing deans as leaders and their teams through professional development programs may instigate transformational change for individuals and the executive leadership team, and if attention is paid to the leader as learner-in-context.
Kinematic Interactions between a Human Musculoskeletal Model and a Lower Limb Exoskeleton
Authors: Varma VS , Rao RY , Budarapu PR , Pandit MK , Vundavilli PR 
Published: July 2023

Abstract
The requirement and applicability of exoskeletons for rehabilitation has been indicated by the amount of efforts invested in research across the world in the past decades. However, commercial exoskeletons are still expensive and limited by the need for adjusting the structure to the individual user. In this study, the human-exoskeleton interactions are explored by designing a lower limb exoskeleton with ten degrees of freedom: six actuated and four passive. Finite element analysis (FEA) of the structure is carried out to observe that the structural design is able to withstand the operating loads. Furthermore, the model is imported to Opensim software and connected with the human musculoskeletal model at the locations where both bodies would be connected in a real scenario, using braces and straps. The connections between the human and exoskele-ton models are modelled as six degrees of freedom joints with limits. Data of two subjects from an openly available gait data-set is used to carry out kinematic simulations. Comparison of five cases: human without an exoskeleton, human-exoskeleton combined, human-exoskeleton combined with locked hip adduction, human-exoskeleton combined with locked hip rotation, and human-exoskeleton combined with locked hip adduction and rotation, proved that the absence of degrees of freedom from the exoskeleton affects and restricts the motion of joints while trying to execute the same walking movement. The amount of movement at the interfaces is estimated by the simulation results. Therefore, a new approach for simulating humanex-oskeleton combined model is presented here.
Retreatment Rates and Postprocedural Complications are Higher than Expected after BPH Surgeries: A US Healthcare Claims and Utilization Study
Authors: Kaplan Steven , Kaufman Ronald , Mueller Tom , Elterman Dean , Chughtai Bilal , Rukstalis Daniel , Woo Henry , Roehrborn Claus 
Published: July 2023

Abstract
Background
Up to 50% of men over 50 and 80% over 80 are affected by BPH. Shared decision-making regarding BPH treatment options can benefit from an improved understanding of relative risks and benefits for various treatments.
Methods
Data for this longitudinal retrospective population-based cohort study were obtained from a random sample of US Medicare and commercial claims (IBM Watson MarketScan) and restricted to men undergoing BPH surgery (TURP, PVP, PUL, WVTT) from 2015 to 2021 across all sites of service. Retreatments included Holmium laser enucleation and index procedures. Main outcomes were rates of retreatment and procedural complications over 1y, identified via CPT and ICD-9/10CM codes. Considered were procedural complications ≥1d post-index treatment and retreatment for patients with ≥1y data. Univariate cumulative incidence estimates, cumulative proportion and log-rank tests justified inclusion for covariate adjustment in Cox proportional hazard models.
Results
43,147 men diagnosed with BPH underwent 22,629 TURP, 11,392 PVP, 7,529 PUL, and 1,597 WVTT. At 1-year post-index: PUL was associated with the lowest rate of complication (PUL 15%, TURP 17%; PVP 19%, ; WVTT 26%); retreatment rates were not different (TURP 5.3%, PVP 5.3%, PUL 5.9%, WVTT 6.2%). At 5yr post-index: retreatment was lowest for TURP (7.0%) and was not significantly different between PVP and PUL (8.9% and 11.6%, respectively).
Conclusions
The results suggest that within one year of BPH surgery, one-in-twenty patients may require retreatment regardless of treatment choice, and for some technologies as many as one-in-four may require treatment for a complication.
Oropharyngeal swelling following a ragweed sublingual immunotherapy
Authors: Lee Soomin , Yang Jim , Lee Erika 
Published: July 2023

Abstract
Background: Sublingual immunotherapy (SLIT) is widely accepted as a safe and effective treatment for allergic rhinitis. Despite severe local and systemic reactions following SLIT are reported to be rare, it is important for patients to be educated and monitored for potential risks throughout treatment. This report presents the first documented case of severe oropharyngeal swelling following SLIT, which necessitated epinephrine treatment and termination of therapy, representing a previously unreported severe local reaction.
Case Presentation: A 30-year-old man with a history of severe seasonal allergic rhinoconjunctivitis and shellfish allergy presented with severe allergic reaction to ragweed SLIT (Ragwitek). The patient had previously received grass subcutaneous immunotherapy and birch SLIT, both of which were well tolerated. On day 9 of Ragwitek SLIT, the patient experienced oropharyngeal swelling, dyspnea, and dysphagia within minutes following administration of therapy, which required epinephrine treatment to alleviate symptoms. The patient had also experienced upper respiratory tract infection symptoms a few days prior which may have exacerbated the severity of the reaction.
Conclusions: This case highlights an occurrence of a rare severe local reaction following SLIT and emphasizes the importance of patient education and close monitoring, especially in those presenting with recurrent local swelling following SLIT. In addition, counselling these patients about the potential risk of oropharyngeal swelling and consideration for prescribing an epinephrine autoinjector is recommended.
Real-world data of atezolizumab in patients with previously treated locally advanced or metastatic urothelial bladder cancer.
Authors: Acedo Rocío Díaz , BANQUERI MERCEDES GALVAN , CRIADO SILVIA ARTACHO , PARRA EVA MARIA FERNANDEZ , GALAN ROCIO JIMENEZ , SANCHEZ ANA ISABEL GAGO , POZO JUAN FRANCISCO MARIN , BAUTISTA MARIA JOSE MARTINEZ 
Published: July 2023

Abstract
Background
Clinical trials of atezolizumab for locally advanced or metastatic urothelial bladder cancer (mUBC) report controversial efficacy data. Moreover, real-world evidence regarding this use is limited.
Aim
We aimed to evaluate the effectiveness of atezolizumab in a real-world population with mUBC, to explore the effectiveness in relation to certain poor prognostic criteria such as performance status by Eastern Oncology Cooperative Group (ECOG), hemoglobin levels, and liver metastases, and to determine the safety profile of atezolizumab.
Methods
This multicenter, retrospective real-world study included previously treated mUBC patients who received atezolizumab. The primary endpoint was overall survival (OS). Furthermore, progression-free survival (PFS), the best response reached, and safety data were analyzed. A descriptive analysis was performed, while OS and PFS were estimated using the Kaplan-Meier method.
Results
185 patients (84.9% men, median age 69 years) were included. Median PFS was 4.8 months [95% confidence interval (CI) 3.6-6.0], and median OS was 20.0 months (95% CI 11.8–28.5), with an objective response rate of 28.1%. OS was higher for patients with ECOG 0–1 [24.5 months (95% CI 14.5–34.6) vs 5.2 (95% CI 4.4-6.0), p = 0.004]; and for patients without liver metastases [25.4 months (95% CI 16.2–34.6) vs 6.4 months (95% CI 4.0-8.1), p = 0.006]. Regarding hemoglobin levels, no survival differences were detected. Adverse events were reported in 55.1% of patients.
Conclusion
In a real-world population with previously treated mUBC, atezolizumab appears to provide a clinically relevant benefit, which is even greater for patients with ECOG 0–1 and those without liver metastases, maintaining an acceptable safety profile.
Long-term clinical outcomes of stereotactic radiotherapy for bilateral vestibular schwannomas in neurofibromatosis type 2 patients
Authors: Puataweepong Putipun , Dhanacha Mantana , Ruangkanchanasetr Rawee , Boonyawan Keeratikarn , Hansasuta Ake , Saetia Kriangsak , Yongvithisatid Pornpan 
Published: July 2023

Abstract
Purpose
The evidence for treating patients with neurofibromatosis 2-related vestibular schwannoma (VS-NF2) using hypofractionated stereotactic radiation therapy (HSRT) is limited. This study aimed to investigate clinical outcomes in patients with VS-NF2 treated with CyberKnife HSRT.
Methods
We retrospectively analyzed 25 NF2 patients with 48 VSs who were treated using CyberKnife HSRT at Ramathibodi Hospital from January 2009 to January 2020.
Results
Median follow-up was 98 months (range, 24–155). Median tumor volume was 2.3 cm3 (range, 0.04–28.3). Median prescribed dose was 18 Gy (range, 18–25) in three fractions (range, 3–5). The 5- and 10-year progression free survival rates were 87% and 80%, respectively. The 5- and 10-year hearing preservation rates were 59% and 35%, respectively. Three patients developed new symptoms associated with transient volume expansion after treatment: hydrocephalus in one, facial weakness in one, and ataxia in one. No patient developed worsening of trigeminal nerve function. No malignant transformation occurred.
Conclusions
CyberKnife HSRT demonstrated excellent long-term tumor control with a low non-auditory complication rate in patients with VS-NF2. However, preservation of hearing remains a major concern.
Metabolomic profiling of amino acids study reveals a distinct diagnostic model for Diabetic kidney disease
Authors: Wang Jiao , Zhou Chunyu , Zhang Qing , Liu Zhangsuo 
Published: July 2023

Abstract
Diabetic kidney disease (DKD), a highly prevalent complication of diabetes mellitus, is a major cause of mortality in patients. However, identifying circulatory markers to diagnose DKD requires a thorough understanding of the metabolic mechanisms of DKD. In this study, we performed ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) to reveal altered metabolic profiles of amino acids (AAs) in patients with DKD. We found decreased plasma levels of histidine and valine, increased urine levels of proline, decreased urine levels of histidine and valine, and increased saliva levels of arginine in patients with DKD compared with the levels in patients with type 2 diabetes mellitus (T2DM) and in healthy controls. Our analyses of the key metabolites and metabolic enzymes involved in histidine and valine metabolism indicated that the AAs level alterations may be due to enhanced carnosine hydrolysis, decreased degradation of homocarnosine and anserine, enhanced histidine methylation, and systemic enhancement of valine metabolism in patients with DKD. Notably, we generated a distinct diagnostic model with an AUC of 0.957 and an accuracy up to 92.2% on the basis of the AA profiles in plasma, urine and saliva differing in patients with DKD using logistic regression and receiver operating characteristic analyses. In conclusion, our results suggest that altered AA metabolic profiles are associated with the progression of DKD. Our DKD diagnostic model on the basis of AA levels in plasma, urine, and saliva may provide a theoretical basis for innovative strategies to diagnose DKD that may replace cumbersome kidney biopsies.