bluuebunny/crossref_metadata_2025_split huggingface dataset:
Response to crizotinib + regorafenib + PD-1 inhibitor in a metastatic BRAF V600E MT colon cancer patients with acquired C-MET amplification and TPM4- ALK fusion: case report and review of literature
Authors: Zhang Shuai , Hu Xueqing , Wang Xiangyang , Zhao Yunbo , Li Zhongkang , Chen Xiaomin , Yuan Mingming , Yu Zicheng , Huang Yingying 
Published: December 2022

Abstract
Colorectal cancer (CRC) with BRAFV600E CRC had a relatively poor prognosis. We report the case of a 49-year-old Chinese male was diagnosed asascending colon adenocarcinoma (cT3N+?M1) with liver metastases. The patient performed next-generation sequencing(NGS) using tissue and circulating tumor DNA (ctDNA), and the results showed a BRAFV600E mutation. He received an initial combination treatment with cetuximab, darafenib, and trametinib with a partial response (PR) assessment. We changed the therapy regimen on this patient several times because of the patient's intolerance to the drugs or the inefficacy of the treatment. During this period, we detected the c-MET amplification and TPM4-ALK fusion by NGS after triplet targeted therapy (tislelizumab, darafenib, and trametinib), thus he was finally treated with PD-1 inhibitor (Tislelizumab), MET/ALK inhibitor (Crozitinib) plus BRAF inhibitor (regorafenib). Imageological examinations showed that PR was achieved and ctDNA sequencing results indicated a significantly reduced BRAF mutation frequency, MET amplification and TPM4-ALK fusion were undetectable. This study reported a co-existence of a BRAFV600E mutation, c-MET amplification and TPM4-ALK fusion in a CRC patient. Administration of crizotinib combined with regorafenib and Tislelizumab obtained an obvious response. Furthermore, continuous ctDNA detection appears to be a promising technique to monitor tumor burden, which may provide better clinical decision support during the disease course.
Skin and ophthalmic complications of chloroquine and hydroxychloroquine in patients with rheumatoid arthritis and systemic lupus erythematous
Authors: Zamani Batool , Hasan‑Abad Amin Moradi , Rafizadeh Seyed Mohsen , Akbari Hossein , Samaei Fateme , Motedayyen Hossein 
Published: December 2022

Abstract

Introduction: Immunosuppressive agents are routinely used to control autoimmunity. However, some adverse events are correlated to their clinical applications. The aim of this study was to study the clinical findings and ocular and cutaneous side effects of chloroquine (CQ) and hydroxychloroquine (HCQ), as current immunosuppressive drugs, in patients with rheumatoid arthritis (RA) and systemic lupus erythematous (SLE).
Materials and Methods: This descriptive study was performed on 360 individuals referred to the Rheumatology clinic during 2003-2020. Demographic characteristics and other information were collected from patients with RA and SLE. Skin and ocular complications were evaluated in patients who were on treatment with CQ and HCQ.
Results: Study populations consisted of 199 subjects with RA and 161 cases with SLE. The frequencies of skin and ocular complications in all patients treated with CQ and HCQ were 42 (11.66%) and 97 (26.9%), respectively. The prevalence of skin complications in patients with RA and SLE was 20 (10.1%) and 22 (13.7%), respectively. The frequencies of ocular complications in patients with RA and SLE were, respectively, 60 (30.2%) and 37 (23%). The results showed that ocular complications in patients with RA were significantly associated with disease duration (p <0.05). Cutaneous and ocular complications in patients showed a significant difference with the cumulative dose of drug (p <0.05).
Conclusion:Based on these findings, treatment with CQ and HCQ participates in some skin and ocular complications in patients with RA and SLE which are largely associated with the duration of disease and treatment.
Experimental study on the effect of thermal-chemical coupling on tension-shear fracture characteristics of cracked Karst limestone
Authors: Zhang Yan , Guo Daojing , Wang Wei , Liu Fengtao , Zeng Jianbin 
Published: December 2022

Abstract
In the natural environment, the main control structural plane of dangerous rock in karst area is subjected to complex coupling effects of temperature, acid rain and tension-shear force. However, the multi-field coupling effect on the stability of dangerous rocks is still unclear. To further probe this issue, first, the chemical solution immersion tests were carried out at pH of 2, 3, 4, 5 and temperature of 20, 30, 40, 60℃ for pre-cracked limestone, and room temperature rock samples at pH of 7 were used as comparison samples. Second, the tension-shear test on the soaked rock samples were conducted using the self-developed tension-shear test device. The crack propagation and failure modes of tension-shear pre-cracked limestone with different temperatures and pH value solutions were analyzed. Finally, the mineral composition, microstructure and damage degree of different rock samples were tested and analyzed by X-ray diffraction test, SEM test and inductively coupled ion emission spectrometer. The test results show that the temperature and acidity are negatively correlated with the tension-shear strength of limestone. The higher the temperature or acidity, the smaller the ultimate tension-shear peak load. The main mineral composition of limestone is calcite, and the pore size on the rock surface reflects the variation trend of cracking under tension-shear loading. The rock mass loss rate is positively correlated with the temperature and negatively correlated with the pH value, both of which can affect the progress of water rock chemistry and have a certain impact on the degree of rock deterioration.
Relationship between gut microbiota and prognosis, clinical characteristics of colorectal cancer based on 16S rRNA sequencing
Authors: Huang Jiannan , Wang Yizhuo , Yuan Chaofeng , Jiang Yang , Chen Xianbin , Wang Mingchuan , Xiao Huijie 
Published: December 2022

Abstract
Purpose
Colorectal cancer is a high incidence tumor, immunotherapy has become a hot topic of research in recent years, at the same time, the dysregulation of intestinal microbiota is also gaining attention because it can lead to changes in body immunity. So, we want to explore the relationship between gut microbiota and colorectal cancer.
Methods
We performed 16S rRNA high-throughput sequencing of tumors and paraneoplastic tissues from 30 patients, followed by at least 5 years of follow-up. Microbiome analysis, survival analysis, and then immunohistochemistry and its correlation with microbiota were performed in 19 of these patients.
Results
OTU13530 and OTU17086, both representing g_Sediminibacterium, showed significant differences in normalized abundance in tumor and paraneoplastic tissues (FDR < 0.05 and log2FC > 1). Both of them correlated with T-stage (p = 0.016, p = 0.024) and Her-2 expression (p = 0.034, p = 0.001). The former correlated with HIF expression (p = 0.017), and the latter with EGFR expression (p = 0.003). OTU3504, representing o_Myxococcales, had a correlation with patient survival (p = 0.015, HR = 28.5(1.9–425.0)), its abundance correlated with tumor neural invasion (p = 0.005) and vascular invasion (p = 0.005).
Conclusion
There is no statistical difference in the diversity and homogeneity of the microbiota between tumor and paraneoplastic tissues. But the abundance of some specific microbiota differed significantly between tumor and paraneoplastic tissues, and these microbiota correlated with patient survival, Her-2, HIF and other proteins expression, T-stage, neurovascular invasion and other clinical traits.
Glycaemic control and therapeutic inertia in patients with CAD and T2DM: a cross-sectional study in the Department of Cardiology
Authors: Zhang Weixia , Peng Qianwen , Zhang Xinle , Xia Qin 
Published: December 2022

Abstract
Background
The purpose of this study was to evaluate glycemic control in type 2 diabetes mellitus (T2DM) patients with coronary artery disease in China, as well as to look into therapeutic inertia among cardiologists.
Methods
From June 2021 to December 2021, a descriptive cross-sectional study was conducted in the Department of Cardiology at Shanghai Ruijin Hospital in China. The method of convenience sampling was used. Patients with coronary artery disease (including acute and chronic coronary syndrome) and T2DM were included in the study. Patients with renal insufficiency (eGFR < 45 ml/min/1.73m2), heart failure (left ventricular ejection fraction, LVEF < 40%), and absence of an HbA1c value during hospitalization were excluded. SPSS 18.0 was used for statistical analysis.
Results
The proportion of diabetic patients achieving the HbA1c target (< 7.0%) among 358 participants was 39.11% (140/358). Glycaemic control was worse in patients with acute coronary syndromes than in those with chronic coronary syndromes (34.63% vs. 45.10%, P < 0.05). The blood pressure control rate was 25.70% (92/358, cut-off 130/80 mmHg), and 41.06% (147/358) of participants had LDL-C levels of < 1.8 mmol/L (70 mg/dL). In the hypoglycemic regimen, therapeutic inertia was present in 55.96% of the study subjects. However, the therapeutic inertia rate varies greatly depending on HbA1c level. The therapeutic inertia rate among patients with HbA1c ≥ 9.0% was significantly lower than the rates in the 7.0-7.9% and 8.0-8.9% groups (P < 0.05).
Conclusions
The Department of Cardiology's glycemic control rate of hospitalized T2DM patients is low, and cardiologists exhibit therapeutic inertia in hypoglycemic regimens.
Investigating coping and stigma in people living with HIV through narrative medicine in the Italian multicentre non-interventional study DIAMANTE
Authors: Antinori Andrea , Vergori Alessandra , Ripamonti Diego , Valenti Daniela , Esposito Vincenzo , Carleo Aurora , Rusconi Stefano , Cascio Antonio , Manzillo Elio , Andreoni Massimo , Orofino Giancarlo , Cappuccio Antonietta , Reale Luigi , Marini Maria Giulia , Mancusi Daniela , Termini Roberta , Uglietti Alessia , Portaro Marianna 
Published: December 2022

Abstract
Antiretroviral therapy (ART) significantly reduced Human Immunodeficiency Virus (HIV) morbidity and mortality; nevertheless, stigma still characterises the living with this condition. This study explored patients’ coping experience by integrating narrative medicine (NM) in a non-interventional clinical trial. From June 2018 to September 2020 the study involved 18 centres across Italy; enrolled patients were both D/C/F/TAF naïve and previously ART-treated. Narratives were collected at enrolment (V1) and last visit (V4) and then independently analysed by three NM specialist researchers through content analysis. One-hundred and fourteen patients completed both V1 and V4 narratives. Supportive relationships with clinicians and undetectable viral load facilitated coping. Conversely, lack of disclosure of HIV-positive status, HIV metaphors, and unwillingness to narrate the life before the diagnosis indicated internalised stigma. This is the first non-interventional study to include narratives as patient reported outcomes (PROs). Improving HIV awareness and reducing the sense of guilt experienced by patients helps to overcome stigma and foster coping.
Comparative outcomes of transcorporeal vs trandiscal anterior endoscopic discectomy for cervical radiculopathy: a systematic review and meta-analysis
Authors: Kongtharvonskul Jatupon , Lekha Punyisa , Arirachakaran Alisara , Woratanarat Patarawan , Thakkinstian Ammarin , Keorochana Gun 
Published: December 2022

Abstract
Introduction: In recent years, the anterior transdiscal approach (td) endoscopic cervical discectomy (PECD) can provide direct decompression for central or paramedian cervical disc herniation, the iatrogenic disc damage may result in decreased intervertebral space. Anterior transcorporeal approach (tc) PECD could enable an individual and adjustable trajectory within the vertebral body under different conditions of disc herniation preserving the motion of the adjacent segment. However, there is no consensus regarding which method is better. Material & Methods: This systematic review was conducted according to the PRISMA guidelines. Relevant studies were identified from Medline and Scopus from inception to Octrober 23th, 2022. Results: Twelve studies and 17 were included for analysis of td PECD and tc PECD. One comparative study was included for comparison of td to tc PECD. A pooled UMD of post-operative neck pain, arm pain (VAS) and disability (NDI) scores of transdiscal PECD and transcorporeal PECD were significantly improved when compared to before surgery. The pooled prevalence of having excellent and good results in modified Macnab criteria, complications and reoperation of td PECD and tc PECD were 0.94 (95%CI: 0.92 to 0.96), 0.03 (95%CI: 0.01 to 0.05), 0.03 (95%CI: 0.01 to 0.04) and 0.90 (95%CI: 0.84 to 0.96), 0.08 (95%CI: 0 to 0.19), 0.05 (95%CI: 0.01 to 0.08). By indirect meta-analysis, td PECD have no significantly difference in all outcomes when compared to tc PECD technique. Conclusion: In post-operative outcomes at 3 to 4 years follow-up, there is no significant difference in all clinical outcomes between the 2 approaches. Trial registration number: Prospero registered No 378776
LKB1 loss rewires JNK-induced apoptotic protein dynamics through NUAKs and sensitizes KRAS-mutant NSCLC to combined KRASG12C + MCL-1 blockade
Authors: Hata Aaron , Li Chendi , Syed Mohammed , Shen Yi , Fraser Cameron , Ouyang Jian , Kreuzer Johannes , Clark Sarah , Oh Audris , Walcott Makeba , Morris Robert , Nabel Christopher , Caenepeel Sean , Saiki Anne , Rex Karen , Lipford J , Heist Rebecca , Lin Jessica , Haas Wilhelm , Sarosiek Kristopher , Hughes Paul 
Published: December 2022

Abstract
The efficacy of molecularly targeted anti-cancer therapies may be limited by the presence of co-occurring mutations within a tumor.1-3 Conversely, these alterations may confer collateral vulnerabilities that can be leveraged for the development of novel therapeutic approaches. KRAS mutant lung cancers are distinguished by recurrent mutations in tumor suppressor genes such as TP53 and STK11/LKB1.4 However, clinically actionable targets associated with these alterations are largely undefined. BH3 mimetics targeting distinct pro-survival BCL-2 family proteins have been proposed to enhance the efficacy of targeted therapies, but no biomarkers exist that can predict which patients are most likely to respond. Here we show that inhibition of oncogenic signaling in KRAS-LKB1 mutant lung cancer cells creates a specific dependency on the anti-apoptotic protein MCL-1 for survival. We find that loss of the LKB1-NUAK signaling axis derepresses a JNK-mediated stress response to KRAS or MEK inhibition, allowing inhibitory phosphorylation of BCL-XL that alters BH3-protein interactions and makes cells vulnerable to concurrent MCL-1 inhibition. These results uncover a previously unknown role for LKB1 in regulating the mitochondrial apoptotic response of cancer cells independent of its tumor suppressor activity mediated by AMPK5-7 and SIK8,9 kinases and suggest a fundamental role for LKB1-NUAKs in suppressing the cellular stress response. Additionally, our study reveals a therapeutically targetable vulnerability in KRAS-LKB1 lung cancer cells and suggests a genotype-informed strategy for improving the efficacy of KRAS-targeted therapies.
Impact of pre-enrichment broth on recovery of S. typhimurium and reformed water activity on dominance and endurance of Salmonella in Indian sweetmeat milk (doodh) peda
Authors: Puttananjaiah Mohan Kumari Honganoor , Viswanath Prema 
Published: December 2022

Abstract
Food-borne outbreaks associated with low water activity (aw) foods involve Salmonella contamination, and its control is a significant challenge. In India, milk (doodh) peda is a low aw traditional and popular food. Accordingly, it is essential to determine the prevalence and survival of Salmonella spp. in artificially spiked milk peda stored for an extended period at different aw. Salmonella spp. was not detected in any of the 25 indigenous peda samples. Salmonella did not grow in low aw. However, S. Typhimurium ATCC 25241, which was inoculated artificially at a level of 1.5x104 CFU/g, survived in the spiked peda sample at 0.75, 0.56, and 0.32 aw. Survival of S. Typhimurium ATCC 25241 was observed for a more extended period (19 days) at lower aw than higher aw. These results confirmed that even though Salmonella spp. was not detected in milk peda samples, but can survive for a long time in contaminated samples. Salmonella survived for a long time by the osmoadaptation mechanism. These results revealed that the survival of S. Typhimurium is influenced by aw, and the prevalence of Salmonella in the peda sample was inversely proportional to aw.
Big data mining to screen hub molecular targets related to metabolic abnormalities, intestinal polyps and colorectal cancer
Authors: Ou Shan , Xu Yun , Liu Qinglan , Yang Tianwen , Chen Wei , Yuan Xiu , Zuo Xin , Yao Jie , Shi Peng 
Published: December 2022

Abstract
Purpose
Intestinal polyps and metabolic syndrome (MetS) are closely related to the occurrence and development of colorectal cancer (CRC). This study aimed to provide a potential target for the mechanism analysis between the occurrence of intestinal polyps with metabolic abnormalities and the development of CRC.
Methods
In this study, we used clinical samples of patients with intestinal polyps with MetS (the control group was patients with common intestinal polyps), screened relevant pathways and genes by transcriptome sequencing and public database association analysis, and verified the targets by immunohistochemistry (IHC).
Results
Compared with the control group, 75 up-regulated and 61 down-regulated differential expressed genes (DEGs) were found in MetS patients with polyps. KEGG enrichment showed that these DEGs were mainly involved in cell cycle and mitotic pathways. By association with the public databases CTD and TCGA, 44 CRC-related hub genes were further screened, among which 8 genes showed the same difference trend in the RNA-Seq and GEPIA-COAD databases. Protein interaction analysis showed that PCP4, OLFM1, FN1, TGF-β3 were all related to MAPK signaling pathway. Tumor correlation analysis showed that FN1, PCP4 and TGF-β3 were higher risk genes but OLFM1 was lower risk gene. Immunohistochemical results showed that only OLFM1 was decreased in MetS patients with intestinal polyps.
Conclusion
In intestinal polyps with MetS, the expression of OLFM1 was reduced and may affect mitosis. Under the influence of MetS and the decrease of OLFM1, exosomes and NF-κB pathway may be involved in this process.
Segmentation and morphometric MRI atlas of the chimpanzee cerebellum
Authors: Parks Ashley Nicole , Bryant Katherine L. , Rankin Erica K. , Smaers Jeroen B. , Hecht Erin E. 
Published: December 2022

Abstract

Increased appreciation of the functional heterogeneity of the cerebellum and its contribution to various neuropsychiatric impairments has sparked a resurgence of interest in its comparative anatomy and evolution. Recent evidence suggests that (1) the cerebellar lobules play a prominent role in cognitive, social, and behavioral computations (Desmond et al. 1997; Schmahmann and Sherman 1998; Stoodley and Schmahmann 2009a), and that (2) select portions of the cerebellum may have undergone evolutionary expansion in some lineages of mammals, including humans (Balsters et al. 2010; Smaers et al. 2018), thus creating a need for a higher neuroanatomical resolution of the cerebellum across a broad comparative sample. Here, we provide a detailed magnetic resonance imaging (MRI) atlas of the chimpanzee cerebellum as well as a methodology for the systematic delineation of the vermal and hemispheric lobules. Group averaging across 67 individuals facilitated the characterization of 32 cerebellar masks across the anterior, posterior, and flocculonodular lobes of the cerebellum. A segmentation protocol, including detailed anatomical definitions of each structure, provides the foundation for the construction of future multimodal cerebellar atlases that can deliver insight into cerebellar evolution and pathology.
VGLL3 expression is associated with macrophage infiltration and predicts poor prognosis in epithelial ovarian cancer
Authors: Haque Razaul , Lee Jaebon , Chung Joon-Yong , Shin Ha-Yeon , Kim Hyosun , Kim Jae-Hoon , Yun Jae Won , Kang Eun-Suk 
Published: December 2022

Abstract
Background
High-grade serous ovarian carcinoma (HGSOC) is the most common histologic type of epithelial ovarian cancer (EOC). Due to its poor survival outcomes, it is essential to identify novel biomarkers and therapeutic targets. The hippo pathway is crucial in various cancers, including gynaecological cancers. Herein, we examined the clinicopathological significance of the key genes of the hippo pathway in HGSOC.
Method
The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) data were curated to analyse the mRNA expression as well as the clinic-pathological association and correlation with immune cell infiltration in HGSOC. The protein levels of significant genes in the HGSOC tissue were analysed using Tissue Microarray (TMA)-based immunohistochemistry. An overall survival analysis was conducted using the log-rank test method and cox regression analysis. Finally, DEGs pathway analysis was performed to identify find the signalling pathways associated with VGLL3.
Result
VGLL3 mRNA expression was significantly correlated with both advanced tumour stage and poor overall survival (OS) (p = 0.046 and p = 0.003, respectively). The result of IHC analysis also supported the association of high VGLL3 protein with poor OS in HGSOC. Further, VGLL3 expression was significantly associated with tumour infiltrating macrophages. VGLL3 expression and macrophages infiltration were both found to be independent prognostic factors (p = 0.003 and p = 0.024, respectively) for HGSOC. VGLL3 was associated with 3,981 gene expressions (p < 2.04e−4), and with four known and three novel cancer-related signalling pathways, thus implying that VGLL3 is involved in the deregulation of many genes and pathways.
Conclusion
Our study revealed that VGLL3 may play a distinct role in clinical outcomes and immune cell infiltration in patients with HGSOC and that it may be a potential prognostic marker of EOC.