bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intratumor microbiome derived glycolysis-lactate signatures depicts immune heterogeneity in lung adenocarcinoma by integration of microbiomic, transcriptomic, proteomic and single-cell data
Authors: Deng Xiaheng , Chen Xiru , Luo Yu , Que Jun , Chen Liang 
Published: August 2023

IntroductionMicrobiome plays roles in lung adenocarcinoma (LUAD) development and anti-tumor treatment efficacy. Aberrant glycolysis in tumor might promote lactate production that alter tumor microenvironment, affecting microbiome, cancer cells and immune cells. We aimed to construct intratumor microbiome score to predict prognosis of LUAD patients and thoroughly investigate glycolysis and lactate signature’s association with LUAD immune cell infiltration.MethodsThe Cancer Genome Atlas-LUAD (TCGA-LUAD) microbiome data was downloaded from cBioPortal and analyzed to examine its association with overall survival to create a prognostic scoring model. Gene Set Enrichment Analysis (GSEA) was used to find each group’s major mechanisms involved. Our study then investigated the glycolysis and lactate pattern in LUAD patients based on 19 genes, which were correlated with the tumor microenvironment (TME) phenotypes and immunotherapy outcomes. We developed a glycolysis-lactate risk score and signature to accurately predict TME phenotypes, prognosis, and response to immunotherapy.ResultsUsing the univariate Cox regression analysis, the abundance of 38 genera were identified with prognostic values and a lung-resident microbial score (LMS) was then developed from the TCGA-LUAD-microbiome dataset. Glycolysis hallmark pathway was significantly enriched in high-LMS group and three distinct glycolysis-lactate patterns were generated. Patients in Cluster1 exhibited unfavorable outcomes and might be insensitive to immunotherapy. Glycolysis-lactate score was constructed for predicting prognosis with high accuracy and validated in external cohorts. Gene signature was developed and this signature was elevated in epithelial cells especially in tumor mass on single-cell level. Finally, we found that the glycolysis-lactate signature levels were consistent with the malignancy of histological subtypes.DiscussionOur study demonstrated that an 18-microbe prognostic score and a 19-gene glycolysis-lactate signature for predicting prognosis of LUAD patients. Our LMS, glycolysis-lactate score and glycolysis-lactate signature have potential roles in precision therapy of LUAD patients.
First identification of canine adenovirus 1 in mink and bioinformatics analysis of its 100 K protein
Authors: Hou Jinyu , Xu Jinfeng , Wang Ben , Zhang Hongling , Yin Baishuang , Li Goujiang , Lei Fashou , Cai Xiaoming , Zhu Yanzhu , Wang Longtao 
Published: August 2023

IntroductionAnimal trade favors the spreading of emerging canine adenovirus 1 (CAdV-1) in mink. Because the 100K protein is not exposed to the viral surface at any stage, it can be used to differentiate the vaccine from wild virus infection. However, no related research has been conducted. This study aimed to find evidence of CAdV-1 in mink and predict the character of the 100K protein in the current circulating CAdV-1 strain of mink.MethodIn this experiment, the identification of CAdV-1, the phylogenetic tree, homology, and bioinformatics analysis of 100K were conducted.ResultsThe results showed that the CAdV-1 was identified in the mink and that its Fiber was located in a separate branch. It was closely related to strains isolated from Norwegian Arctic fox and Red fox. 100K was located in a separate branch, which had the closest genetic relationship with skunks, porcupines, raccoons, and hedgehogs and a far genetic relationship with the strains in dogs. 100K protein is an unstable and hydrophobic protein. It had evidence of selective pressure and recombination, 1 glycosylation site, 48 phosphorylation sites, 60 dominant B cell epitopes, and 9 peptides of MHC-I and MHC-II. Its subcellular localization was mainly in the endoplasmic reticulum and mitochondria. The binding sites of 100K proteins were DBP proteins and 33K proteins.DiscussionThe stains in the mink were different from fox. The exploration of its genomic characteristics will provide us with a deeper understanding of the prevention of canine adenovirus.
Secular trends and features of thalamic hemorrhages compared with other hypertensive intracerebral hemorrhages: an 18-year single-center retrospective assessment
Authors: Katano Hiroyuki , Nishikawa Yusuke , Uchida Mitsuru , Yamanaka Tomoyasu , Hayashi Yuki , Yamada Shigeki , Tanikawa Motoki , Yamada Kazuo , Mase Mitsuhito 
Published: August 2023

IntroductionTrends regarding the locations of hypertensive cerebral hemorrhages are unclear. To clarify hypertensive hemorrhage trends, we investigated intracerebral hemorrhages (ICHs) over an 18-year period, focusing on thalamic hemorrhages compared with other sites of hemorrhages.MethodsWe reviewed the cases of patients hospitalized for hypertensive ICH in 2004–2021 at our hospital; 1,320 eligible patients were registered with a primary ICH/intraventricular hemorrhage. After exclusion criteria were applied, we retrospectively analyzed 1,026 hypertensive ICH cases.ResultsThe proportions of thalamic and subcortical hemorrhages increased over the 18-year period, whereas putaminal hemorrhage decreased. Multivariate logistic regression analyses revealed that for thalamic hemorrhage, ≥200 mmHg systolic blood pressure (p = 0.031), bleeding &lt;15 mL (p = 0.001), and higher modified Rankin scale (mRS) score ≥ 4 at discharge (p = 0.006) were significant variables in the late period (2013–2021) versus the early period (2004–2012), whereas for putaminal hemorrhage, significant factors in the late period were triglyceride &lt;150 mg/dL (p = 0.006) and mRS score ≥ 4 at discharge (p = 0.002). Among the features of the thalamic hemorrhages in the late period revealed by our group comparison with the putaminal and subcortical hemorrhages, the total and subcortical microbleeds were more notable in the thalamic hemorrhages than in the other two types of hemorrhage, whereas cerebellar microbleeds were more prominent when compared only with subcortical hemorrhages.DiscussionOur findings revealed an increasing trend for thalamic hypertensive hemorrhage and a decreasing trend for putaminal hemorrhage. The thalamic hemorrhage increase was observed in both young and older patients, regardless of gender. The main features of thalamic hemorrhage in the late period versus the early period were decrease in larger hemorrhage (≥15 mL) and an increase in cases with higher systolic blood pressure (at least partially involved a small number of untreated hypertensive patients who developed major bleeding). The total and subcortical microbleeds were more notable in the thalamic hemorrhages of the late period than in the putaminal and subcortical hemorrhages. These results may contribute to a better understanding of the recent trends of hypertensive ICHs and may help guide their appropriate treatments for this condition.
Healthcare-associated infections and antimicrobial resistance in severe acquired brain injury: a retrospective multicenter study
Authors: Castellani Giovanna Barbara , Maietti Elisa , Leonardi Gloria , Bertoletti Erik , Trapani Filippo , Battistini Alberto , Tedeschi Sara , Piperno Roberto , Viale Pierluigi 
Published: August 2023

BackgroundRecent studies underscore that healthcare-associated infections (HAIs) and multidrug-resistant (MDR) HAIs affect rehabilitation outcomes and hospital length of stay (LOS) for severe acquired brain injury (sABI).ObjectiveThis study aimed to estimate HAI incidence in different sABI rehabilitation settings and determine risk factors and HAI impact on neuromotor and cognitive recovery.MethodsWe conducted a retrospective multicenter study in two semi-intensive units (SICUs), two high-specialty post-acute units (PAUs), and one long-term care (LTC) rehabilitation facility. Data extraction was performed by experienced clinicians, using a structured Excel file and they agreed upon criteria for case definitions of healthcare. The main outcome measures were the HAI and MDR HAI incidence and the LOS, the functional recovery was measured using the Level of Cognitive Functioning and Disability Rating Scale.ResultsThere were 134 sABI participants. The calculation of the probability level was adjusted for three pairwise comparisons among settings (0.05/3 = 0.017). The HAI and MDR HAI incidences were significantly higher in SICU (3.7 and 1.3 per 100 person-days) than in other settings (LTC: 1.9, p = 0.034 and 0.5, p = 0.026; PAU: 1.2, p &lt; 0.001 and 0.3, p &lt; 0.001). HAI and MDR HAI risk variables included older age, an increased number of devices, and carbapenemase-producing Enterobacteriaceae (CPE) colonization, while a high prealbumin plasma value seemed to have a protective effect.ConclusionHAIs are related to longer LOS, and colonization is associated with poor prognosis and poor functional outcomes with reduced ability to achieve the cognitive capacity of self-care, employability, and independent living. The need to ensure the protection of non-colonized patients, especially those with severe disabilities on admission, is highlighted.
Evaluating the expression of heat shock protein 27 and topoisomerase II α in a retrospective cohort of patients diagnosed with locally advanced breast cancer and treated with neoadjuvant anthracycline-based chemotherapies
Authors: Zhuang Yixuan , Zhang Fan , Xu Yue , He Lifang , Huang Wenhe , Hong Chaoqun , Cui Yukun 
Published: August 2023

BackgroundNeoadjuvant anthracycline-based chemotherapy (NAC) is a major regimen for the treatment of local advanced breast cancer (LABC), while resistance to NAC remains a paramount clinical obstacle. To investigate the role of heat shock protein 27 (Hsp27) and/or topoisomerase IIα (TopoIIα) in LABC patients treated with NAC, we performed this retrospective study.MethodsAssociations of Hsp27 transcripts with clinic-pathological characteristics, survival and drug response were investigated in public databases. Hsp27-related genes were identified, followed by functional enrichment analyses. Besides, two protein-protein interaction networks were built. Then, tumors from 103 patients who were diagnosed with LABC and received NAC were collected, and Hsp27 and TopoIIα were examined by Immunohistochemistry (IHC). Chi-square or Fisher’s exact tests were performed, as well as survival analyses.ResultsEither at the transcriptional level in public databases or at the protein level tested by IHC, a high level of Hsp27 was associated with aggressive tumor characteristics such as lymph node invasion and chemotherapy resistance. Hsp27-related genes mostly involved in the metabolic pathway and the gamete generation biological process. An elevated Hsp27 indicated a poor prognosis in patients with breast cancer (log-rank test P = 0.002 and 0.004 for disease-free survival [DFS] and overall survival [OS], respectively), while it might not be an independent predictor. Of note, tumors with high TopoIIα expression (TopoIIα+) was less likely to express Hsp27 (Hsp27+), in contrast to those with TopoIIα negativity (31.1% vs. 86.2%, P&lt;0.001), and survival analyses revealed that patients with Hsp27+ and TopoIIα- tumors had a significantly lower DFS and OS (log-rank test P &lt; 0.001 and 0.001, respectively), in contrast to the other three groups.ConclusionsHsp27 was associated with aggressive breast cancers and more predictable for the prognosis of LABC patients treated with NAC when concomitantly considering TopoIIα expression.
Prevalence of PIK3CA mutations in Taiwanese patients with breast cancer: a retrospective next-generation sequencing database analysis
Authors: Chao Ta-Chung , Tsai Yi-Fang , Liu Chun-Yu , Lien Pei-Ju , Lin Yen-Shu , Feng Chin-Jung , Chen Yen-Jen , Lai Jiun-I. , Hsu Chih-Yi , Lynn Jiun Jen , Huang Chi-Cheng , Tseng Ling-Ming 
Published: August 2023

BackgroundBreast cancer is the most common cancer type that affects women. In hormone receptor–positive (HR+), human epidermal growth factor receptor 2−negative (HER2–) advanced breast cancer (ABC), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) is the most frequently mutated gene associated with poor prognosis. This study evaluated the frequency of PIK3CA mutations in the Taiwanese breast cancer population.MethodologyThis is a retrospective study; patient data were collected for 2 years from a next-generation sequencing database linked to electronic health records (EHRs). The primary endpoint was the regional prevalence of PIK3CA mutation. The secondary endpoints were to decipher the mutation types across breast cancer subtype, menopausal status, and time to treatment failure after everolimus (an mTOR inhibitor) or cyclin-dependent kinase 4/6 (CDK4/6) inhibitor treatment.ResultsPIK3CA mutations were identified in 278 of 728 patients (38%). PIK3CA mutations were reported in 43% of patients with HR−/HER2+ subtype and 42% of patients with HR+/HER2– postmenopausal status. A lower prevalence of PIK3CA mutations was observed in triple-negative (27%) and HR+/HER2– premenopausal patients (29%). The most common mutation was at exon 20 (H1047R mutation, 41.6%), followed by exon 9 (E545K mutation, 18.9% and E542K mutation, 10.3%). Among patients treated with CDK4/6 inhibitors, the median time to treatment failure was 12 months (95% CI: 7-21 months) in the PIK3CA mutation cohort and 16 months (95% CI: 11-23 months) in the PIK3CA wild-type cohort, whereas patients receiving an mTOR inhibitor reported a median time to treatment failure of 20.5 months (95% CI: 8-33 months) in the PIK3CA mutation cohort and 6 months (95% CI: 2-9 months) in the PIK3CA wild-type cohort.ConclusionA high frequency of PIK3CA mutations was detected in Taiwanese patients with breast cancer, which was consistent with previous studies. Early detection of PIK3CA mutations might influence therapeutic decisions, leading to better treatment outcomes.
Phase 3 CLEAR study in patients with advanced renal cell carcinoma: outcomes in subgroups for the lenvatinib-plus-pembrolizumab and sunitinib arms
Authors: Grünwald Viktor , Powles Thomas , Eto Masatoshi , Kopyltsov Evgeny , Rha Sun Young , Porta Camillo , Motzer Robert , Hutson Thomas E. , Méndez-Vidal María José , Hong Sung-Hoo , Winquist Eric , Goh Jeffrey C. , Maroto Pablo , Buchler Tomas , Takagi Toshio , Burgents Joseph E. , Perini Rodolfo , He Cixin , Okpara Chinyere E. , McKenzie Jodi , Choueiri Toni K. 
Published: August 2023

IntroductionThe phase 3 CLEAR study demonstrated that lenvatinib plus pembrolizumab significantly improved efficacy versus sunitinib as first-line treatment for patients with advanced renal cell carcinoma (RCC). Prognostic features including presence and/or site of baseline metastases, prior nephrectomy, and sarcomatoid features have been associated with disease and treatment success. This subsequent analysis explores outcomes in patients with or without specific prognostic features.MethodsIn CLEAR, patients with clear cell RCC were randomly assigned (1:1:1) to receive either lenvatinib (20 mg/day) plus pembrolizumab (200 mg every 3 weeks), lenvatinib (18 mg/day) plus everolimus (5 mg/day), or sunitinib alone (50 mg/day, 4 weeks on, 2 weeks off). In this report, progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) were all assessed in the lenvatinib-plus-pembrolizumab and the sunitinib arms, based on baseline features: lung metastases, bone metastases, liver metastases, prior nephrectomy, and sarcomatoid histology.ResultsIn all the assessed subgroups, median PFS was longer with lenvatinib-plus-pembrolizumab than with sunitinib treatment, notably among patients with baseline bone metastases (HR 0.33, 95% CI 0.21–0.52) and patients with sarcomatoid features (HR 0.39, 95% CI 0.18–0.84). Median OS favored lenvatinib plus pembrolizumab over sunitinib irrespective of metastatic lesions at baseline, prior nephrectomy, and sarcomatoid features. Of interest, among patients with baseline bone metastases the HR for survival was 0.50 (95% CI 0.30–0.83) and among patients with sarcomatoid features the HR for survival was 0.91 (95% CI 0.32–2.58); though for many groups, median OS was not reached. ORR also favored lenvatinib plus pembrolizumab over sunitinib across all subgroups; similarly, complete responses also followed this pattern.ConclusionEfficacy outcomes improved following treatment with lenvatinib-plus-pembrolizumab versus sunitinib in patients with RCC—irrespective of the presence or absence of baseline lung metastases, baseline bone metastases, baseline liver metastases, prior nephrectomy, or sarcomatoid features. These findings corroborate those of the primary CLEAR study analysis in the overall population and support lenvatinib plus pembrolizumab as a standard of care in 1L treatment for patients with advanced RCC.Clinical trial registrationClinicalTrials.gov, identifier NCT02811861
Genomic signatures and prognosis of advanced stage Chinese pediatric T cell lymphoblastic lymphoma by whole exome sequencing
Authors: Liu Qinglin , Yu Xiang , Wen Jinquan , Yin Nange , Liao Xin , Zou Pinli , Guo Yuxia , Song Lin , Xiao Jianwen 
Published: August 2023

ObjectiveTo investigate the genomic signatures and prognosis of advanced-stage T cell lymphoblastic lymphoma (T-LBL) and to examine the relationship between T-LBL and T cell acute lymphoblastic leukemia (T-ALL).Methods35 Chinese T-LBL children with stage III or IV disease were recruited for this study. They were treated with combination chemotherapy and whole exome sequencing. The relationship of the clinical features, prognosis and specific gene mutations was researched. Gene chips of T-LBL and T-ALL were downloaded from a database, and differential gene expression was analyzed.ResultsGermline causal gene mutations (CARS or MAP2K2) were detected in 2 patients; 3.06 ± 2.21 somatic causal gene mutations were identified in the 35 patients, and somatic mutations were observed in the NOTCH1, FBXW7, PHF6 and JAK3 genes. NOTCH1 mutations were signiﬁcantly associated with FBXW7 mutations, and the age at diagnosis of patients with NOTCH1-FBXW7 mutations was less than that of patients without such mutations (P &lt; 0.05). 32 patients achieved complete remission (CR), and 14 and 18 patients were classified into the intermediate risk (IR) group and high risk (HR) group. During a median follow-up of 44 months, 3 patients relapsed. Three-year prospective event free survival (pEFS) was 82.286%, and no significant differences of pEFS were found for different sexes, ages, or statuses of NOTCH1-FBXW7 mutations, (P &gt; 0.05); however, the mean survival time of the IR group was longer than that of the HR group (P &lt; 0.05). Differential expression of genes in the T-LBL and/or T-ALL datasets was analyzed using the R package limma, and 1/3 of the differentially expressed genes were found in both the T-ALL and T-LBL datasets. High expression of PI3K-Akt signal pathway genes and the USP34 gene was found in the T-LBL dataset.ConclusionAlthough T-ALL and T-LBL both originate from precursor T-cells and are considered different manifestations of the same disease and the outcome of T-LBL is favorable when using T-ALL-based chemotherapy, there are differences in the gene distribution between T-LBL and T-ALL. It seems that the PI3K-Akt signaling pathway and the USP34 gene play important roles in T-LBL, but medicines targeting the USP34 gene or the PI3K-Akt pathway may be invalid.
Metabolic syndrome in patients with obsessive-compulsive disorder
Authors: Khalkhali Mohammadrasoul , Rasekh Kiarash , Eslamdoust-Siahestalkhi Fatemeh , Farrahi Hassan , Zare Roghaye 
Published: August 2023

ObjectiveMetabolic syndrome (MetS) is a collection of chemical and clinical risk factors. Patients with obsessive-compulsive disorder (OCD) might be at risk of MetS. This study aimed to investigate the prevalence and clinical correlates of MetS in an Iranian clinical sample of patients with OCD.MethodsWe included 107 patients with OCD in a cross-sectional study. Demographic and clinical characteristics including OC symptoms, duration of treatment, age of onset, medications history, and comorbidity with other psychiatric disorders were collected.ResultsThe prevalence of MetS was 39.2%. Abdominal obesity was the most frequent component of MetS (68.2%), followed by low high-density lipoprotein cholesterol (50.5%). High serum triglycerides, high fasting serum glucose, high systolic blood pressure, and high diastolic blood pressure were observed in 47.7, 20.6, 18.7, and 9.3% of patients, respectively. Patients with MetS were older, married, had a low education level, had a high body mass index, and had no aggressive OC symptoms. MetS was not associated with psychiatric disorders comorbidities, age of onset, and duration of treatment.ConclusionThe results of this study were in line with the results of other studies that reported the poor health status of patients with OCD. A large number of patients are affected or are at risk of developing MetS. These patients need medical care along with the usual OCD treatments.
Applications of indocyanine green (ICG) fluorescence technology in open surgery: preliminary experience in pediatric surgery
Authors: Esposito Ciro , Lepore Benedetta , Cerulo Mariapina , Del Conte Fulvia , Coppola Vincenzo , Esposito Giovanni , Carulli Roberto , Carraturo Francesca , Escolino Maria 
Published: August 2023

BackgroundIndocyanine green fluorescence technology (ICG) in pediatric minimally invasive surgery has undergone an important improvement in the last 5 years. However, its use in open surgery is still limited. In this paper, we aim to report our preliminary experience with Rubina® lens ICG fluorescence technology in combination with the IMAGE1 S™ system from KARL STORZ in open excision of masses in children.MethodsThe records of 18 patients undergoing open surgery for head, neck and thorax masses between September and November 2022 were retrospectively reviewed. Rubina® lens ICG fluorescence technology system was used in all the cases. In 10 cases we adopted the holding arm system and in 8 cases the hand-held technique. Data about patients' demographics, surgery and outcomes were collected and analyzed through the following criteria: mass localization, intraoperative time (min), ICG administration (ml), intraoperative complications, postoperative complications.ResultsA total of 18 patients were operated: 4 thyroglossal duct cysts, 3 supraorbital cysts, 2 neck masses, 2 pre-auricular and 2 scalp cysts, 2 gynecomastias, 2 lymphangiomas, 1 nose mass. In all the cases, intralesional injection of 0.5–1 ml of ICG solution was performed peri-operatively. Mean operative time was 58.4 min (35–134 min). Postoperative complications included seroma formation in 2 cases. Surgical pathology reports confirmed complete mass excision in all the cases.ConclusionBased on our preliminary experience, ICG fluorescence guided surgery using Rubina® lens system was very helpful also in open surgery procedures. Rubina® lens system permits to have a very low complication rate, a time-saving surgery, a real time reliability of anatomic structures and an excellent clinical safety. In our experience, holding arm system seems more comfortable than hand-held system. However, further cases need to be performed to evaluate the exact role and to identify new indications of this technique in open pediatric surgical procedures.