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36895898

A rare case of hepatic epitheliod hemangioendothelioma.

Hepatic epithelioid hemangioendothelioma (HEHE) is an extremely mon tumor of the liver. It typically lacks recognizable clinical signs and is diagnosed with the aid of imaging and bined with immunohistochemical analysis. We discuss the case of a 40-year-old woman with HEHE. The aim of this case report and literature review is to increase doctors' knowledge of HEHE and reduce the incidence of missed clinical diagnoses.

36895899

Headache and orofacial pain: A traffic-light prognosis-based management approach for the musculoskeletal practice.

Headache (HA) is one of the most prevalent disabling conditions worldwide and is classified as either primary or secondary. Orofacial pain (OFP) is a frequent pain perceived in the face and/or the oral cavity and is generally distinct from a headache, according to anatomical definitions. Based on the up-to-date classification of the International Headache Society, out of more than 300 specific types of HA only two are directly attributed to the musculoskeletal system: The cervicogenic HA and HA attributed to temporomandibular disorders. Because patients with HA and/or OFP frequently seek help in the musculoskeletal practice, a clear and tailored prognosis-based classification system is required to achieve better clinical es.

36895900

Low-dose vs. standard-dose alteplase for Chinese patients with acute ischemic stroke: A propensity score analysis.

Previous studies have stimulated debates on low-dose alteplase administration in acute ischemic stroke (AIS) among the Asian population. We sought to evaluate the safety and efficacy of low-dose alteplase in Chinese patients with AIS using a real-world registry.

36895901

Association between preoperative hematocrit and postoperative 30-day mortality in adult patients with tumor craniotomy.

The purpose of this research was to synthesize the American College of Surgeons National Surgical Quality Improvement Program database to investigate the link between preoperative hematocrit and postoperative 30-day mortality in patients with tumor craniotomy.

36895902

Machine learning-based prediction of clinical outcomes after first-ever ischemic stroke.

Accurate prediction of clinical es in individual patients following acute stroke is vital for healthcare providers to optimize treatment strategies and plan further patient care. Here, we use advanced machine learning (ML) techniques to pare the prediction of functional recovery, cognitive function, depression, and mortality of first-ever ischemic stroke patients and to identify the leading prognostic factors.

36895903

A deep learning approach to predict collateral flow in stroke patients using radiomic features from perfusion images.

Collateral circulation results from specialized anastomotic channels which are capable of providing oxygenated blood to regions promised blood flow caused by arterial obstruction. The quality of collateral circulation has been established as a key factor in determining the likelihood of a favorable clinical e and goes a long way to determining the choice of a stroke care model. Though many imaging and grading methods exist for quantifying collateral blood flow, the actual grading is mostly done through manual inspection. This approach is associated with a number of challenges. First, it is time-consuming. Second, there is a high tendency for bias and inconsistency in the final grade assigned to a patient depending on the experience level of the clinician. We present a multi-stage deep learning approach to predict collateral flow grading in stroke patients based on radiomic features extracted from MR perfusion data. First, we formulate a region of interest detection task as a reinforcement learning problem and train a deep learning network to automatically detect the occluded region within the 3D MR perfusion volumes. Second, we extract radiomic features from the obtained region of interest through local image descriptors and denoising auto-encoders. Finally, we apply a convolutional neural network and other machine learning classifiers to the extracted radiomic features to automatically predict the collateral flow grading of the given patient volume as one of three severity classes - no flow (0), moderate flow (1), and good flow (2). Results from our experiments show an overall accuracy of 72% in the three-class prediction task. With an inter-observer agreement of 16% and a maximum intra-observer agreement of 74% in a similar experiment, our automated deep learning approach demonstrates a parable to expert grading, is faster than visual inspection, and eliminates the problem of grading bias.

36895904

Peripheral eosinophil trends and clinical outcomes after non-traumatic subarachnoid hemorrhage.

Uncontrolled systemic inflammation after non-traumatic subarachnoid hemorrhage (SAH) is associated with worse es. Changes in the peripheral eosinophil count have been linked to worse clinical es after ischemic stroke, intracerebral hemorrhage, and traumatic brain injury. We aimed to investigate the association of eosinophil counts with clinical es after SAH.

36895905

An overview of clinical cerebral microdialysis in acute brain injury.

Cerebral microdialysis may be used in patients with severe brain injury to monitor their cerebral physiology. In this article we provide a concise synopsis with illustrations and original images of catheter types, their structure, and how they function. Where and how catheters are inserted, their identification on imaging modalities (CT and MRI), together with the roles of glucose, lactate/pyruvate ratio, glutamate, glycerol and urea are summarized in acute brain injury. The research applications of microdialysis including pharmacokinetic studies, retromicrodialysis, and its use as a biomarker for efficacy of potential therapies are outlined. Finally, we explore limitations and pitfalls of the technique, as well as potential improvements and future work that is needed to progress and expand the use of this technology.

36895907

Case report: JAK inhibition as promising treatment option of fatal RVCLS due to

Autosomal dominant mutations in the C-terminal part of

36895908

Incidence of Guillain-Barré syndrome in South Korea during the early COVID-19 pandemic.

Guillain-Barré syndrome (GBS) is an immune-mediated polyradiculoneuropathy, often triggered by infection. We aimed to investigate how the incidence of GBS changed in the early stages of the coronavirus 2019 (COVID-19) pandemic when nationwide infections declined due to non-pharmaceutical interventions.

36895909

Stroke and the risk of gastrointestinal disorders: A Mendelian randomization study.

The issue of whether a stroke is causally related to gastrointestinal disorders was still not satisfactorily understood. Therefore, we investigated if there is a connection between stroke and the most prevalent gastrointestinal disorders, including peptic ulcer disease (PUD), gastroesophageal reflux disease (GERD), irritable bowel syndrome (IBS), and inflammatory bowel disease (IBD).

36895910

The development of neurocritical care in China from the perspective of evaluation and treatment of critical neurological diseases.

To understand the varieties, evaluation, treatment, and prognosis of severe neurological diseases using the third NCU survey in China.

36895911

Value of neutrophil-to-lymphocyte ratio for diagnosing sarcopenia in patients undergoing maintenance hemodialysis and efficacy of Baduanjin exercise combined with nutritional support.

To investigate the value of neutrophil-to-lymphocyte ratio (NLR) for diagnosing sarcopenia in patients undergoing maintenance hemodialysis (MHD) and efficacy of Baduanjin bined with nutritional support on MHD patients with sarcopenia.

36895912

Case series: Immune checkpoint inhibitor-induced transverse myelitis.

Increasing implementation of the highly efficacious immune checkpoint inhibitors (ICIs) has raised awareness of their plications in the form of immune-related adverse events (irAEs). Transverse myelitis following ICIs is thought to be a rare but serious neurologic irAE and knowledge is limited about this distinct clinical entity.

36895914

Superior survival outcome of blinatumomab compared with conventional chemotherapy for adult patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia: a propensity score-matched cohort analysis.

Blinatumomab showed a plete remission (CR) rate and a safe bridging to allogeneic hematopoietic cell transplantation (allo-HCT) in adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (R/R BCP-ALL).

36895915

Efficacy and safety of venetoclax-based regimens for the treatment of relapsed/refractory multiple myeloma: a systemic review and meta-analysis.

Patients with relapsed/refractory multiple myeloma (RRMM) usually have dismal prognostic es. Venetoclax, a selective inhibitor of antiapoptotic protein B-cell lymphoma-2 (BCL-2), demonstrates antimyeloma activity in plasma cells with t(11;14) or high BCL-2 expression.

36895916

Application of the Novel Grading System of Invasive Pulmonary Adenocarcinoma in a Real Diagnostic Scenario: A Brief Report of 9353 Cases.

The International Association for the Study of Lung Cancer proposed a novel grading system of invasive pulmonary adenocarcinoma (IPA), but the application of this grading system and its genotypic characterization in the real diagnostic scenario has never been reported.

36895918

Targeting lung cancer brain metastases: a narrative review of emerging insights for anaplastic lymphoma kinase (

Lung cancer monly associated with brain metastasis formation, and certain subtypes, such as anaplastic lymphoma kinase (

36895919

Supervision by an experienced surgeon can reduce the learning curve of uniportal thoracoscopic lobectomy.

This retrospective study was performed to investigate the learning curve of uniportal thoracoscopic lobectomy with ND2a-1 or greater lymphadenectomy for two senior surgeons, and to evaluate how supervision affected the learning curve.

36895920

Peripheral T-cell receptor repertoire dynamics in small cell lung cancer.

Identifying a circulating biomarker predictive of immune checkpoint inhibitor (ICI) benefit in patients with small cell lung cancer (SCLC) remains an unmet need. Characteristics of peripheral and intratumoral T-cell receptor (TCR) repertoires have been shown to predict clinical es in non-small cell lung cancer (NSCLC). Recognizing a knowledge gap, we sought to characterize circulating TCR repertoires and their relationship with clinical es in SCLC.

36895922

Early-stage anaplastic lymphoma kinase (

While anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) are standard of care treatment for metastatic

36895924

Optimal first-line treatment for metastatic ALK+ non-small cell lung cancer-a narrative review.

First-line treatment options for patients with advanced non-small cell lung cancer (aNSCLC) whose tumors harbour anaplastic lymphoma kinase (

36895926

Efficacy of immune checkpoint inhibitors in advanced non-small cell lung cancer harboring

Despite immune checkpoint inhibitors (ICI) being widely used to treat patients with advanced non-small cell lung cancer (NSCLC), few studies examine the role of ICI in patients with proto-oncogene B-Raf, serine/threonine kinase (

36895930

Targeted therapies for KRAS-mutant non-small cell lung cancer: from preclinical studies to clinical development-a narrative review.

Non-small cell lung cancer (NSCLC) with Kirsten rat a viral oncogene homolog (

36895931

Pembrolizumab plus pemetrexed-carboplatin combination in first-line treatment of advanced non-squamous non-small cell lung cancer: a multicenter real-life study (CAP29).

bined with chemotherapy is now first-line standard of care in advanced non-small cell lung cancer. This real-life study aimed to assess efficacy and safety of carboplatin-pemetrexed plus pembrolizumab in advanced non-squamous non-small cell lung cancer.

36895932

Integrative genomic profiling reveals characteristics of lymph node metastasis in small cell lung cancer.

Small cell lung cancer (SCLC) is the most aggressive lung cancer subtype, with more than 70% of patients having metastatic disease and a poor prognosis. However, no integrated multi-omics analysis has been performed to explore novel differentially expressed genes (DEGs) or significantly mutated genes (SMGs) associated with lymph node metastasis (LNM) in SCLC.

36895933

Narrative review: immunotherapy in anaplastic lymphoma kinase (ALK)+ lung cancer-current status and future directions.

Patients with metastatic anaplastic lymphoma kinase (ALK)+ non-small cell lung cancer (NSCLC) often experience years of disease control on targeted therapies but the disease eventually develops resistance and progresses. Multiple clinical trial efforts to incorporate PD-1/PD-L1 immunotherapy into the treatment paradigm for ALK+ NSCLC have resulted in significant toxicities without clear improvement in patient es. Observations from clinical trials, translational studies, and preclinical models suggest the immune system interacts with ALK+ NSCLC and this interaction is heightened with the initiation of targeted therapy. The objective of this review is to summarize knowledge to date about current and potential immunotherapy approaches for patients with ALK+ NSCLC.

36895934

Integrated analysis reveals the microenvironment of non-small cell lung cancer and a macrophage-related prognostic model.

In the treatment of non-small cell lung cancer (NSCLC), recent advances in immunotherapy have heralded a new era. Despite the success of immune therapy, a subset of patients persistently fails to respond. Therefore, to better improve the efficacy of immunotherapy and achieve the purpose of precision therapy, the research and exploration of tumor immunotherapy biomarkers have received much attention.

36895935

A novel cuproptosis-related lncRNA signature to predict prognosis and immune landscape of lung adenocarcinoma.

Cuproptosis, a recently discovered type of programmed cell death (PCD), paves a new avenue for cancer treatment. It has been revealed that PCD-related lncRNAs play a critical role in various biological processes of lung adenocarcinoma (LUAD). However, the role of cuproptosis-related lncRNA (CuRLs) remains unclear. This study aimed to identify and validate a CuRLs-based signature for the prognostic prediction of patients with LUAD.

36895936

Cost-effectiveness of diagnostic tests during follow-up in lung cancer patients: an evidence-based study.

Many patients with non-metastatic non-small cell lung cancer (NSCLC) are cured by surgery but part of them develop recurrence. Strategies are needed to identify these relapses. Currently, there is no consensus on the follow-up schedule after curative resection for patients with NSCLC. The objective of this study is to analyze the diagnostic capacity of the tests performed during follow-up after surgery.

36895937

Differential organ-specific tumor response to first-line immune checkpoint inhibitor therapy in non-small cell lung cancer-a retrospective cohort study.

Immune checkpoint inhibitors (ICIs) possess remarkable clinical effectiveness in non-small cell lung cancer (NSCLC). Different immune profiles of tumors may play a key role in the efficacy of treatment with ICIs. This article aimed to determine the differential organ responses to ICI in individuals with metastatic NSCLC.

36895938

Erratum to neoadjuvant chemo-immunotherapy for lung cancer: how much is too much?

[This corrects the article DOI: 10.21037/tlcr-22-828.].

36895943

Vitamin D supplementation is effective for olanzapine-induced dyslipidemia.

Olanzapine is an atypical antipsychotic drug that is clinically applied in patients with schizophrenia. It increases the risk of dyslipidemia, a disturbance of lipid metabolic homeostasis, usually characterized by increased low-density lipoprotein (LDL) cholesterol and triglycerides, and panied by decreased high-density lipoprotein (HDL) in the serum. In this study, analyzing the FDA Adverse Event Reporting System, JMDC insurance claims, and electronic medical records from Nihon University School of Medicine revealed that a co-treated drug, vitamin D, can reduce the incidence of olanzapine-induced dyslipidemia. In the following experimental validations of this hypothesis, short-term oral olanzapine administration in mice caused a simultaneous increase and decrease in the levels of LDL and HDL cholesterol, respectively, while the triglyceride level remained unaffected. Cholecalciferol supplementation attenuated these deteriorations in blood lipid profiles. RNA-seq analysis was conducted on three cell types that are closely related to maintaining cholesterol metabolic balance (hepatocytes, adipocytes, and C2C12) to verify the direct effects of olanzapine and the functional metabolites of cholecalciferol (calcifediol and calcitriol). Consequently, the expression of cholesterol-biosynthesis-related genes was reduced in calcifediol- and calcitriol-treated C2C12 cells, which was likely to be mediated by activating the vitamin D receptor that subsequently inhibited the cholesterol biosynthesis process

36895945

Therapeutic effects on cancer of the active ingredients in rhizoma paridis.

Cancer is a major threat to human health, with high mortality and a low cure rate, continuously challenging public health worldwide. Extensive clinical application of traditional Chinese medicine (TCM) for patients with poor es of radiotherapy and chemotherapy provides a new direction in anticancer therapy. Anticancer mechanisms of the active ingredients in TCM have also been extensively studied in the medical field. As a type of TCM against cancer, Rhizoma Paridis (Chinese name: Chonglou) has important antitumor effects in clinical application. The main active ingredients of Rhizoma Paridis (e.g., total saponins, polyphyllin I, polyphyllin II, polyphyllin VI, and polyphyllin VII) have shown strong antitumor activities in various cancers, such as breast cancer, lung cancer, colorectal cancer, hepatocellular carcinoma (HCC), and gastric cancer. Rhizoma Paridis also has low concentrations of certain other active ingredients with antitumor effects, such as saponins polyphyllin E, polyphyllin H,

36895946

The pharmacogenetics of

Pharmacogenetics has potential for optimizing use of psychotropics.

36895942

Trained immunity in monocyte/macrophage: Novel mechanism of phytochemicals in the treatment of atherosclerotic cardiovascular disease.

Atherosclerosis (AS) is the pathology of atherosclerotic cardiovascular diseases (ASCVD), characterized by persistent chronic inflammation in the vessel wall, in which monocytes/macrophages play a key role. It has been reported that innate immune system cells can assume a persistent proinflammatory state after short stimulation with endogenous atherogenic stimuli. The pathogenesis of AS can be influenced by this persistent hyperactivation of the innate immune system, which is termed trained immunity. Trained immunity has also been implicated as a key pathological mechanism, leading to persistent chronic inflammation in AS. Trained immunity is mediated

36895949

Pharmacological and toxicological studies of a novel goserelin acetate extended-release microspheres in rats.

LY01005 is an investigational new drug product of goserelin acetate which is formulated as extended-release microspheres for intramuscular injection. To support the proposed clinical trials and marketing application of LY01005, pharmacodynamics, pharmacokinetics and toxicity studies were performed in rats. In the pharmacological study in rats, LY01005 induced an initial supra-physiological level increase of testosterone at 24 h post-dosing which then rapidly fell to castration level. The potency of LY01005 parable to parator Zoladex

36895950

OC-01 (Varenicline Solution) Nasal Spray for the Treatment of Dry Eye Disease Signs and Symptoms in Subjects with Autoimmune Disease: Integrated Data from ONSET-1 and ONSET-2.

We evaluate the treatment effect of OC-01 (varenicline solution) nasal spray (VNS) in dry eye disease (DED) subjects from two randomized trials who self-reported autoimmune disease (AID).

36895951

Magnitude of Maladaptive Coping Strategy and Its Associated Factors Among Adult Glaucoma Patients Attending Tertiary Eye Care Center in Ethiopia.

Coping strategy is the mechanism by which patients adjust to the condition they face. It can be adaptive or maladaptive. A maladaptive coping strategy is a harmful and ineffective way of dealing with stress or anxiety. It mon among patients with chronic illnesses. Despite Ethiopia having a greater a prevalence, there was no evidence of patients with a using maladaptive coping mechanisms.

36895952

Gene network landscape of mouse splenocytes reveals integrin complex as the A151 ODN-responsive hub molecule in the immune transcriptome.

Homeostatic restoration of an inflammatory response requires quenching of the immune system after pathogen threats vanish. A continued assault orchestrated by host defense results in tissue destruction or autoimmunity. A151 is the epitome of synthetic oligodeoxynucleotides (ODNs) that curb the immune response by a subset of white corpuscles through repetitive telomere-derived TTAGGG sequences. Currently, the genuine effect of A151 on the immune cell transcriptome remains unknown. Here, we leveraged an integrative approach where weighted gene co-expression network analysis (WGCNA), differential gene expression analysis, and gene set enrichment analysis (GSEA) of our in-house microarray datasets aided our understanding of how A151 ODN suppresses the immune response in mouse splenocytes. Our bioinformatics results, together with experimental validations, indicated that A151 ODN acts ponents of plexes,

36895954

Variability in objective sleep is associated with Alzheimer's pathology and cognition.

Both sleep duration and sleep efficiency have been associated with risk of Alzheimer's disease, suggesting that interventions to promote optimal sleep may be a way to reduce Alzheimer's disease risk. However, studies often focus on average sleep measures, usually from self-report questionnaires, ignoring the role of intra-individual variability in sleep across nights quantified from objective sleep measures. The current cross-sectional study sought to investigate the role of intra-individual variability in accelerometer-based objective sleep duration and sleep efficiency in relation to

36895955

Characterization of spastic paraplegia in a family with a novel

Spastic paraparesis has been described to occur in 13.7% of

36895956

Brain network mapping and glioma pathophysiology.

Adult diffuse gliomas are among the most difficult brain disorders to treat in part due to a lack of clarity regarding the anatomical origins and mechanisms of migration of the tumours. While the importance of studying networks of glioma spread has been recognized for at least 80 years, the ability to carry out such investigations in humans has emerged only recently. Here, prehensively review the fields of brain network mapping and glioma biology to provide a primer for investigators interested in merging these areas of inquiry for the purposes of translational research. Specifically, we trace the historical development of ideas in both brain network mapping and glioma biology, highlighting studies that explore clinical applications of network neuroscience, cells-of-origin of diffuse glioma and glioma-neuronal interactions. We discuss recent research that has merged neuro-oncology and network neuroscience, finding that the spatial distribution patterns of gliomas follow intrinsic functional and structural brain networks. Ultimately, we call for more contributions from network neuroimaging to realize the translational potential of cancer neuroscience.

36895957

Investigating genotype-phenotype relationship of extreme neuropathic pain disorders in a UK national cohort.

The aims of our study were to use whole genome sequencing in a cross-sectional cohort of patients to identify new variants in genes implicated in neuropathic pain, to determine the prevalence of known pathogenic variants and to understand the relationship between pathogenic variants and clinical presentation. Patients with extreme neuropathic pain phenotypes (both sensory loss and gain) were recruited from secondary care clinics in the UK and underwent whole genome sequencing as part of the National Institute for Health and Care Research Bioresource Rare Diseases project. A multidisciplinary team assessed the pathogenicity of rare variants in genes previously known to cause neuropathic pain disorders and exploratory analysis of research candidate genes pleted. Association testing for genes carrying rare variants pleted using the gene-wise approach of bined burden and ponent test SKAT-O. Patch clamp analysis was performed on transfected HEK293T cells for research candidate variants of genes encoding ion channels. The results include the following: (i) Medically actionable variants were found in 12% of study participants (205 recruited), including known pathogenic variants:

36895958

A convergent subcortical signature to explain the common efficacy of subthalamic and pallidal deep brain stimulation.

This mentary refers to 'Globus pallidus internus deep brain stimulation evokes resonant neural activity in Parkinson's disease', by Johnson

36895959

Modular segregation drives causality of the dynamic oscillatory network responses during threat processing.

Physiological responses to threat and stress stimuli entrain synchronized neural oscillations among cerebral networks. Network architecture and adaptation may play a critical role in achieving optimal physiological responses, while alteration can lead to mental dysfunction. We reconstructed cortical and sub-cortical source time series from high-density electroencephalography, which were then fed munity architecture analysis. Dynamic alterations were evaluated in terms of flexibility, clustering coefficient and global and local efficiency, as parameters munity allegiance. Transcranial magnetic stimulation was applied over the dorsomedial prefrontal cortex during the time window relevant for physiological threat processing and effective connectivity puted to test the causality of network dynamics. A theta munity re-organization was evident in key anatomical regions conforming the central executive, salience network and default mode networks during instructed threat processing. Increased network flexibility entrained the physiological responses to threat processing. The effective connectivity analysis showed that information flow differed between theta and alpha bands and were modulated by transcranial magnetic stimulation in salience and default mode networks during threat processing. Theta oscillations drive munity network re-organization during threat processing. munity switches may modulate the directionality of information flow and determine physiological responses relevant to mental health.

36895960

Globus pallidus internus deep brain stimulation evokes resonant neural activity in Parkinson's disease.

Globus pallidus internus deep brain stimulation is an established therapy for patients with medication-refractory Parkinson's disease. Clinical es are highly dependent on applying stimulation to precise locations in the brain. However, robust neurophysiological markers are needed to determine the optimal electrode location and to guide postoperative stimulation parameter selection. In this study, we evaluated evoked resonant neural activity in the pallidum as a potential intraoperative marker to optimize targeting and stimulation parameter selection to improve es of deep brain stimulation for Parkinson's disease. Intraoperative local field potential recordings were acquired in 22 patients with Parkinson's disease undergoing globus pallidus internus deep brain stimulation implantation (

36895962

Amygdala dismantled: the role of amygdala subregions in epilepsy.

This mentary refers to: 'Amygdala subnuclear volumes in temporal lobe epilepsy with hippocampal sclerosis and in non-lesional patients' by Ballerini

36895963

MicroRNA-365 inhibits ovarian cancer progression by targeting Wnt5a [Retraction].

[This retracts the article on p. 1096 in vol. 7, PMID: 28560060.].

36895961

Decreased myelin proteins in brain donors exposed to football-related repetitive head impacts.

American football players and other individuals exposed to repetitive head impacts can exhibit a constellation of later-life cognitive and neuropsychiatric symptoms. While tau-based diseases such as chronic traumatic encephalopathy can underpin certain symptoms, contributions from non-tau pathologies from repetitive head impacts are increasingly recognized. We examined cross-sectional associations between myelin integrity using immunoassays for myelin-associated glycoprotein and proteolipid protein 1 with risk factors and clinical es in brain donors exposed to repetitive head impacts from American football. Immunoassays for myelin-associated glycoprotein and proteolipid protein 1 were conducted on dorsolateral frontal white matter tissue samples of 205 male brain donors. Proxies of exposure to repetitive head impacts included years of exposure and age of first exposure to American football play. pleted the Functional Activities Questionnaire, Behavior Rating Inventory of Executive Function-Adult Version (Behavioral Regulation Index), and Barratt Impulsiveness Scale-11. Associations between myelin-associated glycoprotein and proteolipid protein 1 with exposure proxies and clinical scales were tested. Of the 205 male brain donors who played amateur and professional football, the mean age was 67.17 (SD = 16.78), and 75.9% (

36895964

Tumor-derived Immunoglobulin-like transcript 4 facilitates angiogenesis of colorectal cancer.

Current anti-angiogenic therapies have changed the paradigm of treating colorectal cancer (CRC) patients with advanced diseases. However, the clinical response rate is still low at less than 10% due largely plex angiogenic factors released by tumor cells. Exploring novel mechanisms of tumor angiogenesis and identifying alternative targets bination therapies are therefore essential to effective inhibition of tumor vascularization and CRC development. Immunoglobulin-like transcript 4 (ILT4), initially identified as a suppressor of myeloid cell activity, is enriched in solid tumor cells. ILT4 favors tumor progression by inducing tumor malignant biologies as well as an immunosuppressive microenvironment. However, whether and how tumor-derived ILT4 orchestrates tumor angiogenesis is still undetermined. Here we found that tumor-derived ILT4 was positively correlated with microvessel density in CRC tissues. ILT4 induced the migration and tube formation of HUVECs

36895966

N7-methylguanosine regulatory genes well represented by METTL1 define vastly different prognostic, immune and therapy landscapes in adrenocortical carcinoma.

Although N7-methylguanosine (m7G) is one of the most frequent RNA modifications, it has received little attention. Adrenocortical carcinoma (ACC) is a highly malignant and easily metastatic tumor, eagerly needing for novel therapeutic strategy. Herein, a novel m7G risk signature (METTL1, NCBP1, NUDT1 and NUDT5) was constructed using the Lasso regression analysis. It possessed highly prognostic value and could improve the predictive accuracy and clinical making-decision benefit of traditional prognostic model. Its prognostic value was also successfully validated in GSE19750 cohort. Through CIBERSORT, ESTIMATE, ssGSEA and GSEA analyzes, high-m7G risk score was found to be closely associated with increased enrichment of glycolysis and suppression of anti-cancer immune response. Therapeutic correlation of m7G risk signature was also investigated using tumor mutation burden, the expressions of immune checkpoints, TIDE score, IMvigor 210 cohort and TCGA cohort. m7G risk score was a potential biomarker for predicting the efficacy of ICBs and mitotane. Furthermore, we explored the biofunctions of METTL1 in ACC cells through a series of experimentations. Overexpression of METTL1 stimulated the proliferation, migration and invasion of H295R and SW13 cells. Immunofluorescence assays revealed that the infiltrating levels of CD8+ T cells was lower and that of macrophages was higher in clinical ACC samples with high METTL1 pared to that in low expression ones. Silencing METTL1 could significantly inhibited tumor growth in mouse xenograft model. Western blot assays showed that METTL1 positively regulated the expression of glycolysis rate-limiting enzyme HK1. Finally, miR-885-5p and CEBPB were predicted as the upstream regulators of METTL1 through data mining of the public databases. In conclusions, m7G regulatory genes well represented by METTL1 profoundly affected the prognosis, tumor immune, therapeutic es, and malignant progression of ACC.

36895967

Oral squamous cell carcinoma cell-derived GM-CSF regulates PD-L1 expression in tumor-associated macrophages through the JAK2/STAT3 signaling pathway.

Previous study reported that gastric cancer-derived granulocyte-macrophage colony-stimulating factor (GM-CSF) could mediate neutrophil activation and induce PD-L1 expression through JAK2/STAT3 signaling pathway. Moreover, this pathway in various cancers could also regulate PD-L1 expression of tumor cells. Therefore, our study aimed to investigate whether the JAK2/STAT3 pathway regulates PD-L1 expression in tumor-associated macrophages (TAMs) in oral squamous cell carcinoma (OSCC), which can help us achieve further understanding of immune escape mechanisms in OSCC. We induced human monocytes THP-1 into M0, M1, and M2 macrophages, and applied them mon medium and tumor-conditioned medium, the latter was collected from two types of OSCC cell line. Western blot and RT-PCR were used to detect PD-L1 expression and activation of JAK2/STAT3 pathway in macrophages under various conditions. We found that GM-CSF in tumor-conditioned medium from OSCC cells increased PD-L1 expression in M0 macrophages in a time-dependent manner. Moreover, both GM-CSF neutralizing antibody and JAK2/STAT3 pathway inhibitor AG490 could inhibited its up-regulation. In the meantime, we confirmed that GM-CSF indeed acted through JAK2/STAT3 pathway by measuring phosphorylation of key proteins in this pathway. Therefore, we concluded that OSCC cell-derived GM-CSF was able to up-regulate PD-L1 expression in TAMs through JAK2/STAT3 signaling pathway.

36895968

Onvansertib inhibits the proliferation and improves the cisplatin-resistance of lung adenocarcinoma via β-catenin/c-Myc signaling pathway.

Polo-like kinase 1 (PLK1) is a key regulator of cell division, and its abnormal expression is related to the progression and prognosis of cancers. However, the effect of PLK1 inhibitor onvansertib on the growth of lung adenocarcinoma (LUAD) has not been explored. In this study, we performed a series of bioinformatics and experimental analyses prehensively investigate the role of PLK1 in LUAD. We used CCK-8 assay and colony formation assay to evaluate the growth inhibitory ability of onvansertib. Furthermore, flow cytometry was applied to exploit the effects of onvansertib on cell cycle, apoptosis, and mitochondrial membrane potential. Moreover, the therapeutic potential of onvansertib was assessed in vivo by using xenograft tumor and patient-derived xenograft (PDX) models. We found that onvansertib significantly induced the apoptosis and inhibited the proliferation and migration of LUAD cells. Mechanistically, onvansertib arrested the cells at G2/M phase and enhanced the levels of reactive oxidative species in LUAD. Accordingly, onvansertib regulated the expression of glycolysis-related genes and improved the cisplatin resistance in LUAD. Notably, the protein levels of β-catenin and c-Myc were affected by onvansertib. Taken together, our findings provide insight into the function of onvansertib and shed light on the potential clinical application of onvansertib for the treatment of patients with LUAD.

36895969

Incidence trends in triple-negative breast cancer among women in the United States from 2010 to 2019 by race/ethnicity, age and tumor stage.

There were substantial ethnic disparities in the incidence rates of triple-negative breast cancer, but few studies were conducted on the incidence trend of triple-negative breast cancer by race/ethnicity. This study aimed to address the longer trends in the incidence of triple-negative breast cancer by race/ethnicity in women from 2010 to 2019, examine the incidence trends by patient age, tumor stage and time periods, and explore the changing proportions of ponent receptors over time for triple-negative breast cancer. Our study identified 573,168 women with incident breast cancer at age ≥20 years between 2010 and 2019 in 18 SEER (Surveillance, Epidemiology, and End Results) registries. Of them, 62,623 (10.9%) were incident triple-negative breast cancer and 510,545 were non-triple negative breast cancer cases. The denominator of population included 320,117,009 women aged ≥20 in the same SEER areas. The study found that overall age-adjusted incidence rate of triple-negative breast cancer in women aged ≥20 years was 18.3 cases per 100,000 women. Age-adjusted incidence rate of triple-negative breast cancer was the highest in black women (33.8 cases per 100,000 women), followed by white (17.5), American Indian and Alaska Native (AIAN) (14.7), Hispanic (14.7), and Asian women (12.4). The significantly higher age-adjusted incidence of triple-negative breast cancer in black women pared to white women appeared to be limited in younger women aged 20-44 only. Annual percentage changes in age-adjusted incidence of triple-negative breast cancer slightly decreased insignificantly in white, black and Asian women aged 20-44 and 45-54 years. There was a statistically significant annual percentage increase in age-adjusted incidence of triple-negative breast cancer in Asian and black women aged ≥55 years. In conclusion, there was a significantly higher incidence of triple-negative breast cancer in black women aged 20-44 years. From 2010 to 2019, there were no significant annual percentage changes in age-adjusted incidence of triple-negative breast cancer in all ethnic groups of women aged <55 years, with the exception of a significant decrease among AIAN women aged 45-54 years. However, there was a statistically significant annual percentage increase in age-adjusted incidence of triple-negative breast cancer in Asian and black women aged ≥55 years.

36895970

A combination of BR101801 and venetoclax enhances antitumor effect in DLBCL cells via c-Myc/Bcl-2/Mcl-1 triple targeting.

Double hit diffuse large B-cell lymphoma (DLBCL) with rearrangement and overexpression of both c-Myc and Bcl-2 responds poorly to standard R-CHOP therapy. In a recent phase I study, Venetoclax (ABT-199) targeting Bcl-2 also exhibited disappointing response rates in patients with relapsed/refractory DLBCL, suggesting that targeting only Bcl-2 is not sufficient for achieving successful efficacy due to the concurrent oncogenic function of c-Myc expression and drug resistance following an increase in Mcl-1. Therefore, co-targeting c-Myc and Mcl-1 could be a binatorial strategy to enhance the efficacy of Venetoclax. In this study, BR101801 a novel drug for DLBCL, effectively inhibited DLBCL cell growth/proliferation, induced cell cycle arrest, and markedly inhibited G0/G1 arrest. The apoptotic effect of BR101801 was also observed by increased Cytochrome C, cleaved PARP, and Annexin V-positive cell populations. This anti-cancer effect of BR101801 was confirmed in animal models, where it effectively inhibited tumor growth by reducing the expression of both c-Myc and Mcl-1. Furthermore, BR101801 exhibited a significant synergistic antitumor effect even in late xenograft models bined with Venetoclax. Our data strongly suggest that c-Myc/Bcl-2/Mcl-1 triple targeting through bination of BR101801 and Venetoclax could be a potential clinical option for double-hit DLBCL.

36895971

Identification of necroptosis-related genes as prognostic indicators for lower-grade glioma.

The purpose of this research is to develop a predictive model based on necroptosis-related genes to predict the prognosis and survival of lower grade gliomas (LGGs) efficiently. To achieve this goal, we searched for differentially expressed necrotizing apoptosis-related genes using the TCGA and CGGA databases. To construct a prognostic model, LASSO Cox and COX regression analyses were conducted on the differentially expressed genes. In this study, three genes were used to develop a prognostic model of necrotizing apoptosis, and all samples were split into high- and low-risk groups. We observed that patients with a high-risk score had a worse overall survival rate (OS) than those with a low-risk score. In the TCGA and CGGA cohorts, the nomogram plot showed a high capacity to predict overall survival of LGG patients. GSEA analysis revealed that the high-risk group was enriched for inflammatory responses, tumor-related pathways, and pathological processes. Additionally, the high-risk score was associated with invading immune cell expression. In conclusion, our predictive model based on necroptosis-related genes in LGG was shown to be effective in the diagnosis and could predict the prognosis of LGG. In addition, we identified possible targets related to necroptosis-related genes for glioma therapy in this study.

36895972

Endogenous HMGB1 regulates GSDME-mediated pyroptosis via ROS/ERK1/2/caspase-3/GSDME signaling in neuroblastoma.

Pyroptosis, a newly discovered mode of programmed cell death (PCD), is important in the regulation of cancer development. High mobility group box 1 (HMGB1) is a non-histone nuclear protein that is closely related to tumor development and chemotherapy resistance. However, whether endogenous HMGB1 regulates pyroptosis in neuroblastoma remains unknown. Here, we showed that HMGB1 showed ubiquitous higher expression in SH-SY5Y cells and clinical tumors, and was positively correlated with the risk factors of patients with neuroblastoma. Knockdown of GSDME or pharmacological inhibition of caspase-3 blocked pyroptosis and cytosolic translocation of HMGB1. Moreover, knockdown of HMGB1 inhibited cisplatin (DDP) or etoposide (VP16)-induced pyroptosis by decreasing GSDME-NT and cleaved caspase-3 expression, resulting in cell blebbing and LDH release. Knockdown of HMGB1 expression increased the sensitivity of SH-SY5Y cells to chemotherapy and switched pyroptosis to apoptosis. Furthermore, the ROS/ERK1/2/caspase-3/GSDME pathway was found to be functionally connected with DDP or VP16-induced pyroptosis. Hydrogen peroxide (H

36895973

Erratum: Interleukin-17 promotes the development of ovarian cancer through upregulation of MTA1 expression.

[This corrects the article on p. 5646 in vol. 12, PMID: 36628289.].

36895974

Sporadic hyperplastic polyp associated with above-average risk of developing metachronous colorectal cancer.

Post-colonoscopy surveillance interval for colorectal polyps depends on the size, number, and pathological classification of removed polyps. The risk of sporadic hyperplastic polyps (HPs) for developing colorectal adenocarcinoma remains debatable due to limited data. We aimed to evaluate the risk of metachronous colorectal cancer (CRC) in patients with sporadic HPs. A total of 249 patients with historical HP(s) diagnosed in 2003 were included as the disease group, and 393 patients without any polyp as the control group. All historical HPs were reclassified into SSA or true HP based on the recent 2010 and 2019 World Health Organization (WHO) criteria. Polyp size was measured under light microscope. Patients developed CRC were identified from the Tumor Registry database. Each tumor was tested for DNA mismatch repair proteins (MMR) by immunohistochemistry. Results showed that 21 (8%) and 48 (19%) historical HPs were reclassified as SSAs based on the 2010 and 2019 WHO criteria, respectively. The mean polyp size of SSAs (6.7 mm) was significantly larger than HPs (3.3 mm) (P<0.0001). For polyp size ≥5 mm, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for diagnosing SSA was 90%, 90%, 46%, and 99%, respectively. Left-sided polyps with size <5 mm were 100% of HPs. Five of 249 (2%) patients developed metachronous CRC during the 14-year follow-up from 2003 to 2017, including 2 of 21 (9.5%) patients with SSA diagnosed at intervals of 2.5 and 7 years, and 3 of 228 (1.3%) patients with HP(s) at 7, 10.3, and 11.9 years. Two of 5 cancers showed MMR deficiency with concurrent loss of MLH1/PMS2. Based on the 2019 WHO criteria, the rate of developing metachronous CRC in patients with SSA (P=0.0116) and HP (P=0.0384) was significantly higher than the control group, and no significant difference was observed between patients with SSA and with HP (P=0.241) in this cohort. Patients with either SSA or HP also had higher risk of CRC than average-risk US population (P=0.0002 and 0.0001, respectively). Our data add a new line of evidence that patients with sporadic HP are associated with above-average risk of developing metachronous CRC. Post-polypectomy surveillance for sporadic HP may be adjusted in future practice given the low but increased risk of developing CRC.

36895975

Identification and validation of the cellular senescence-related molecular subtypes of triple negative breast cancer via integrating bulk and single-cell RNA sequencing data.

Patients with triple-negative breast cancer (TNBC) reportedly benefit from immune checkpoint blockade (ICB) therapy. However, the subtype-specific vulnerabilities of ICB in TNBC remain unclear. As plex interplay between cellular senescence and anti-tumor immunity has been previously discussed, we aimed to identify markers related to cellular senescence that may serve as potential predictors of response to ICB in TNBC. We used three transcriptomic datasets derived from ICB-treated breast cancer samples at both scRNA-seq and bulk-RNA-seq levels to define the subtype-specific vulnerabilities of ICB in TNBC. Differences in the molecular features and immune cell infiltration among the different TNBC subtypes were further explored using two scRNA-seq, three bulk-RNA-seq, and two proteomic datasets. 18 TNBC samples were collected and utilized to verify the association between gene expression and immune cell infiltration by multiplex immunohistochemistry (mIHC). A specific type of cellular senescence was found to be significantly associated with response to ICB in TNBC. We employed the expression of four senescence-related genes, namely

36895976

Antineoplastic efficacy profiles of avapritinib and nintedanib in

Systemic mastocytosis (SM) is a hematopoietic neoplasm with plex pathology and a variable clinical course. Clinical symptoms result from organ infiltration by mast cells (MC) and the effects of pro-inflammatory mediators released during MC activation. In SM, growth and survival of MC are triggered by various oncogenic mutant-forms of the tyrosine kinase KIT. The most prevalent variant, D816V, confers resistance against various KIT-targeting drugs, including imatinib. We examined the effects of two novel promising KIT D816V-targeting drugs, avapritinib and nintedanib, on growth, survival, and activation of neoplastic MC pared their activity profiles with that of midostaurin. Avapritinib was found to suppress growth of HMC-1.1 cells (

36895977

Moxibustion attenuates liver metastasis of colorectal cancer by regulating gut microbial dysbiosis.

The liver metastasis is the primary factor attributing to the poor prognosis of colorectal cancer (CRC). Moxibustion has been used clinically against multiple malignancies. In this study, we explored the safety, efficacy, and the potential functional mechanisms of moxibustion in modulating the liver metastasis of CRC by using GFP-HCT116 cells-derived CRC liver metastasis model in Balb/c nude mice. The tumor bearing mice were randomly divided into model control and treatment groups. Moxibustion was applied to the BL18 and ST36 acupoints. CRC liver metastasis was measured by fluorescence imaging. Furthermore, feces from all mice were collected, and 16S rRNA analysis was used to assess their microbial diversity, which was analyzed for its correlation with liver metastasis. Our results indicated that the liver metastasis rate was decreased significantly by moxibustion treatment. Moxibustion treatment also caused statistically significant changes in the gut microbe population, suggesting that moxibustion reshaped the imbalanced gut microbiota in the CRC liver metastasis mice. Therefore, our findings provide new insights into the host-microbe crosstalk during CRC liver metastasis and suggest moxibustion could inhibit CRC liver metastasis by remolding the structure of destructed gut munity. Moxibustion may serve as plementary and alternative therapy for the treatment of patients with CRC liver metastasis.

36895978

Iron oxide nanoparticles inhibit tumor growth by ferroptosis in diffuse large B-cell lymphoma.

Since the approval by the Food and Drug Administration (FDA), ferumoxytol and other iron oxide nanoparticles (IONs) have been widely used as iron supplements for patients with iron deficiency. Meanwhile, IONs have also been used as contrast agents in magnetic resonance imaging and as drug carriers. Importantly, IONs have demonstrated a significant inhibitory effect on the growth of tumors, including hematopoietic and lymphoid tumors, such as leukemia. In this study, we further demonstrated the effect of IONs on inhibiting the growth of diffuse large B-cell lymphoma (DLBCL) cells by enhancing ferroptosis-mediated cell death. IONs treatment caused an accumulation of intracellular ferrous iron and the onset of lipid peroxidation in DLBCL cells as well as the suppressed expression of anti-ferroptosis protein Glutathione Peroxidase 4 (GPX4), thereby leading to increased ferroptosis. Mechanistically, IONs increased cellular lipid peroxidation through the generation of ROS via the Fenton reaction and regulating the iron metabolism-related proteins, such as ferroportin (FPN) and transferrin receptor (TFR), which elevated the intracellular labile iron pool (LIP). Hence, our findings suggest the potential therapeutic effect of IONs on the treatment of patients with DLBCL.

36895979

Concomitant delivery of doxorubicin and cisplatin through liposome-based thermosensitive nanoparticles: perspective in the treatment of cancer in animal models.

The temperature sensitive liposomal formulations are a promising tool to improve the therapeutic index of the drugs with minimal toxicity. The aim of this study was to investigate the potential of itant delivery of cisplatin (Cis) and doxorubicin (Dox) containing thermosensitive liposomes (TSLs) with mild hyperthermia against cancer

36895980

SIRT6 drives sensitivity to ferroptosis in anaplastic thyroid cancer through NCOA4-dependent autophagy.

The sirtuin family has been reported to participate in the regulation of oxidative stress, cancer metabolism, aging, and so on. However, few studies have demonstrated its role in ferroptosis. Our previous studies confirmed that SIRT6 is upregulated in thyroid cancer and associated with cancer development by regulating glycolysis and autophagy. In this research, we aimed to elucidate the association between SIRT6 and ferroptosis. RSL3, erastin, ML210, and ML162 were applied to induce ferroptosis. Cell death and lipid peroxidation were measured by flow cytometry. We found that overexpression of SIRT6 significantly increased the sensitivity of cells to ferroptosis, whereas knockout of SIRT6 promoted resistance to ferroptosis. Furthermore, we demonstrated that SIRT6 induced NCOA4-dependent autophagic degradation of ferritin, thus driving sensitivity to ferroptosis. The clinically used ferroptosis inducer sulfasalazine showed promising therapeutic effects on SIRT6-upregulated thyroid cancer cells in vivo. In conclusion, our research demonstrated SIRT6-driven sensitivity to ferroptosis via NCOA4-dependent autophagy and proposed ferroptosis inducers as promising therapeutic agents for anaplastic thyroid cancer patients.

36895981

Prognostic value of genetic alterations and

The current standard front-line therapy for patients with diffuse large-B cell lymphoma (DLBCL)-rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP)-is found to be ineffective in up to one-third of them. Thus, their early identification is an important step towards testing alternative treatment options. In this retrospective study, we assessed the ability of

36895982

POM121 promotes the proliferation and metastasis of gastric cancer via PI3K/AKT/MYC pathway.

Nuclear pore membrane protein 121 (POM121) is a part of the nuclear plex, which regulates intracellular signaling and maintains normal cellular functions. However, the role of POM121 in gastric cancer (GC) remains unclear. Quantitative real-time polymerase chain reaction was performed to detect POM121 mRNA in 36 pairs of GC and adjacent non-tumor tissues. POM121 protein expression was determined by immunohistochemistry in 648 GC tissues and 121 normal gastric tissues. Connections between POM121 levels, clinicopathological parameters, and the prognosis of GC patients were explored. The influence of POM121 on proliferation, migration, and invasion was detected in vitro and vivo. The mechanism underlying the involvement of POM121 in GC progression was demonstrated via bioinformatics analysis and Western blot. Both the mRNA and protein levels of POM121 in GC tissues were higher than those in normal gastric tissues. High POM121 expression in GC was associated with deep invasion, advanced distant metastases and TNM stage, and positive HER2 expression. A negative connection was found between POM121 expression and the overall survival (OS) of GC patients. Downregulation of POM121 inhibited the proliferation, clone formation, migration, and invasion of GC cells, and overexpression of POM121 showed the opposite trend. POM121 promoted the phosphorylation of PI3K/AKT pathway and increased the expression of MYC. In conclusion, this study suggested that POM121 has the potential to act as an independent prognostic factor for GC patients.

36895983

Prognostic and therapeutic value of serum lipids and a new IPI score system based on apolipoprotein A-I in diffuse large B-cell lymphoma.

Lipid metabolism is associated with lymphomagenesis and functions as a new therapeutic target in patients with lymphoma. Several serum lipids and lipoproteins have prognostic value in solid tumors; however, their value in diffuse large B-cell lymphoma (DLBCL) has been poorly described. We retrospectively analyzed pared pre-treatment serum lipid and lipoprotein levels, including triacylglycerol (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoprotein A-I (ApoA-I), and apolipoprotein B (ApoB) between 105 DLBCL and 105 controls (no DLBCL). The prognostic significance of serum lipid and lipoprotein levels was determined using univariate and multivariate Cox proportional hazards models. The primary es, overall survival (OS) and progression-free survival (PFS), were assessed by the Kaplan-Meier method. bined the International Prognostic Index (IPI) with ApoA-I to build a nomogram model (IPI-A) to predict the OS and PFS of DLBCL. Serum TG, LDL-C, HDL-C, ApoA-I, and ApoB levels were significantly lower in the DLBCL patients than in controls and significantly increased after chemotherapy. Multivariate analyses showed that the ApoA-I level was an independent predictor of OS and PFS. In addition, our findings indicated that the prognostic index IPI-A significantly improves risk prediction over the traditional IPI score system. ApoA-I is an independent prognostic factor associated with poor OS and PFS in DLBCL patients. Our findings suggested that IPI-A is a prognostic index accurately used for risk assessment in patients with DLBCL.

36895984

Protective role of mineralocorticoid receptor signaling in urothelial tumorigenesis.

The expression status of mineralocorticoid receptor (MR) and its biological significance in human urothelial carcinoma remain unknown. The present study aimed to determine the functional role of MR in the development of urothelial cancer. In human normal urothelial SVHUC cells with exposure to a chemical carcinogen 3-methylcholanthrene (MCA), we assessed the effects of a natural MR ligand, aldosterone, and 3 MR antagonists, including spironolactone, eplerenone, and esaxerenone, as well as knockdown of MR via shRNA virus infection, on their neoplastic/malignant transformation. The

36895985

Exosomal long noncoding RNA AGAP2-AS1 regulates trastuzumab resistance via inducing autophagy in breast cancer [Retraction].

[This retracts the article on p. 1962 in vol. 11, PMID: 34094664.].

36895986

Prediction model of hepatocellular carcinoma in patients with hepatitis B virus-related compensated cirrhosis receiving antiviral therapy.

The feasibility and performance of predicting hepatocellular carcinoma (HCC) using bined albumin-bilirubin (ALBI) and fibrosis-4 (FIB-4)-based model remain unclear in patients pensated cirrhosis and chronic hepatitis B (CHB) receiving long-term nucleos(t)ide analog (NA) therapy. We enrolled 1158 NA-naïve patients pensated cirrhosis and CHB treated with entecavir or tenofovir disoproxil fumarate. The patients' baseline characteristics, hepatic reserve, and fibrosis indices were analyzed. bination of ALBI and FIB-4 was used to develop a prediction model of HCC. In this cohort, the cumulative incidence rates of HCC at 3, 5, and 10 years were 8.1%, 13.2%, and 24.1%, respectively. bination of ALBI and FIB-4, Diabetes mellitus, and Alpha-fetoprotein (AFDA) were independent risk factors for HCC. bined ALBI and FIB-4-based prediction model (i.e., AFDA) stratified the cumulative risk of HCC into three groups (with risk scores of 0, 1-3, 4-6) among all patients (P < 0.001). AFDA exhibited the highest area under the receiver operating characteristic (0.6812) for predicting HCC, which was higher than those of aMAP (0.6591), mPAGE-B (0.6465), CAMD (0.6379), and THRI (0.6356) and significantly higher than those of PAGE-B (0.6246), AASL-HCC (0.6242), and HCC-RESCUE (0.6242). Patients with a total score of 0 (n = 187, 16.1% of total patients) had the lowest cumulative HCC incidence of 3.4% at 5 years. bined ALBI and FIB-4-based prediction model can stratify the risk of HCC in patients pensated cirrhosis and CHB receiving NA therapy.

36895987

Combined CRAFITY score and α-fetoprotein response predicts treatment outcomes in patients with unresectable hepatocellular carcinoma receiving anti-programmed death-1 blockade-based immunotherapy.

Biomarkers for predicting the treatment efficacy of immune checkpoint inhibitor (ICI)-based therapy in patients with unresectable hepatocellular carcinoma (uHCC) are crucial. Previous studies demonstrated that C-reactive protein and alpha-fetoprotein (AFP) in immunotherapy (CRAFITY) score at baseline predicted treatment es and that patients with uHCC with AFP response, defined as > 15% decline in AFP level within the initial 3 months of ICI-based therapy, had favorable es when receiving ICI-based therapy. However, whether bination of CRAFITY score and AFP response could be used to predict treatment efficacy of programmed death-1 (PD-1) blockade-based therapy in uHCC patients remains unclear. We retrospectively enrolled 110 consecutive uHCC patients from May 2017 to March 2022. The median ICI treatment duration was 2.85 (1.67-6.63) months, and 87 patients bination therapies. The objective response and disease control rates were 21.8% and 46.4%, respectively. The duration of progression-free survival (PFS) and overall survival (OS) was 2.87 (2.16-3.58) months and 8.20 (4.23-12.17) months, respectively. We categorized patients into three groups based on CRAFITY score (2 vs 0/1) and AFP response: patients with a CRAFITY score of 0/1 and AFP response (Group 1), those with a CRAFITY score of 2 and no AFP response (group 3), and those who did not belong to Group 1 and 3 (i.e., Group 2). bination of CRAFITY score and AFP response could predict disease control and could predict pared with CRAFITY score or AFP response alone. bination of CRAFITY score and AFP response was an independent predictor of OS (Group 2 vs Group 1, HR: 4.513, 95% CI 1.990-10.234; Group 3 vs Group 1, HR: 3.551, 95% CI 1.544-8.168). Our findings indicated that bination of CRAFITY score and AFP response could predict disease control, PFS, and OS in uHCC patients receiving PD-1 blockade-based immunotherapy.

36895988

EIF4A3 induced circABCA5 promotes the gastric cancer progression by SPI1 mediated IL6/JAK2/STAT3 signaling.

Gastric cancer is one of the mon malignancies of the digestive system with high mortality rates. Recent studies have demonstrated that circRNAs are novel noncoding RNAs that play vital roles in the tumorigenesis and development of gastric cancer. Our study found a novel circRNA, namely, hsa_circ_0107595 (also called circABCA5), that is overexpressed in gastric cancer based on circRNA sequencing. qPCR demonstrated its overexpression in gastric cancer specimens. The overexpression or knockdown of circABCA5 in gastric cancer cell lines was achieved by lentiviral-mediated transfection. All MTS, EdU, Transwell and migration assays and xenograft experiments demonstrated that circABCA5 could promote gastric cancer proliferation, invasion, and migration in vitro and in vivo. Mechanistically, both RIP and RNA pulldown assays confirmed that circABCA5 could bind to the SPI1 protein, upregulate SPI1 expression, and promote its nuclear translocation. SPI1 could further promote the malignant phenotype of gastric cancer by activating IL6/JAK2/STAT3 signaling. In addition, EIF4A3 could directly bind to circABCA5, promoting its stability and expression. Our study reveals that circABCA5 plays a vital role in the diagnosis and prognosis of gastric cancer and may even be developed as a molecular target for the treatment of gastric cancer.

36895989

Long-Term Responders to Erlotinib for Pulmonary Adenocarcinoma With Wild-Type Epidermal Growth Factor Receptor: Two Case Reports and a Single-Institutional Retrospective Study.

Erlotinib is an oral and reversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor and is now used exclusively to non-small cell lung carcinoma (NSCLC) harboring mutated EGFR. However, there was historically a transient period when erlotinib was widely used regardless of EGFR mutation status. We report two cases with adenocarcinoma and wild-type EGFR status, which responded to erlotinib for unusual long time. We also retrospectively analyzed patients with adenocarcinoma and wild-type EGFR mutation status who had received erlotinib-containing regimen in our hospital. A 60-year-old woman received the second-line and tri-weekly regimen of pemetrexed (500 mg/m

36895991

Postoperative Chemotherapy After Surgical Resection of Metachronous Metastases of Colorectal Cancer: A Systematic Review.

Currently, 6 months of perioperative or adjuvant chemotherapy (ACT) is a standard treatment option after radical surgical removal of metachronous metastases in patients with metastatic colorectal cancer (CRC). Data show that ACT improves relapse-free survival in such patients, although no difference in overall survival rate was observed. We perform a systematic review to evaluate the efficacy of adjuvant chemotherapy after radical resection of metachronous metastases in CRC.

36895992

The Impact of DTYMK as a Prognostic Marker in Colorectal Cancer.

Overexpression of deoxythymidylate kinase (DTYMK) has been associated with more aggressiveness and pathological behaviors in hepatocellular carcinoma (HCC) and non-small cell lung cancer (NSCLC). However, the expression of DTYMK and its prognostic significance in colorectal cancer (CRC) patients are yet unknown. The goal of this study was to investigate the DTYMK immunohistochemistry reactivity in CRC tissues and to see how it correlated with various histological and clinical features as well as survival.

36895993

High Body Mass Index Was Associated With Human Epidermal Growth Factor Receptor 2-Positivity, Histological Grade and Disease Progression Differently by Age.

Breast cancer is the monly occurring cancer among women. The relationship between the obesity paradox and breast cancer is still unclear. The goal of this study is to elucidate the association between high body mass index (BMI) and pathological findings by age.

36895994

Carcinoembryonic Antigen, Carbohydrate Antigen 19-9, Cancer Antigen 125, Prostate-Specific Antigen and Other Cancer Markers: A Primer on Commonly Used Cancer Markers.

Cancer markers are molecules produced by cancer cells which may serve to identify the presence of cancer. Cancer markers can be differentiated as serum-based, radiology-based and tissue-based, and are one of the most important tools in diagnosing, staging and monitoring of treatment of many cancers. The most used cancer markers are serum cancer markers due to its relative ease and lower cost of testing. However, serum cancer markers have poor mass screening utilization due to poor positive predictive value. Several markers such as prostate-specific antigen (PSA), beta-human chorionic gonadotropin (B-hCG), alpha-fetoprotein (AFP), and lactate dehydrogenase (LDH) are used to aid in diagnosis of cancer in cases of high suspicion. Serum markers such as carcinoembryonic antigen (CEA), AFP, carbohydrate antigen 19-9 (CA 19-9), and 5-hydroxyindoleacetic acid (5-HIAA) play a significant role in assessing disease prognosis as well as response to treatment. This work reviews the role of some of the biomarkers in the diagnosis and treatment of cancer.

36895995

Association Between Expression of Vitamin D Receptor and Insulin-Like Growth Factor 1 Receptor Among Breast Cancer Patients.

Vitamin D receptor (VDR) and insulin-like growth factor 1 receptor (IGF1R) are known to be involved in breast cancer (BC) progression. Our previous work reported a correlation of differential localization of IGF1R with hormone receptor status in BC. A recent report described VDR and IGF1R as potential indicators of BC prognosis, but their interplay was not discussed. The present study focused on understanding the association of VDR expression with IGF1R activation, different molecular markers, and subtypes of BC.

36895996

Incidence of Breast Cancer and Enterococcus Infection: A Retrospective Analysis.

Enterococci role in the microbiome remains controversial, and researches regarding enterococcal infection (EI) and its sequelae are limited. The gut microbiome has shown to play an important role in immunology and cancer. Recent data have suggested a relationship between the gut microbiome and breast cancer (BC).

36895997

Estradiol Levels and Chemotherapy in Breast Cancer Patients: A Prospective Clinical Study.

Breast cancer remains a global health issue, including in Indonesia, which has a relatively high incidence of breast cancer. Several theories have proved the role of estrogen in breast cancer carcinogenesis, but there is yet to be a preventive measure against breast cancer. Chemotherapy is one of the therapeutic modalities for breast cancer that disturbs ovarian function in producing estrogen due to damaged ovarian granulosa cells. Chemotherapy es an alternative option to decreasing circulating estradiol levels through interventions in ovarian functions, either by surgery, such as oophorectomy, or medications that disturb the ovarian functions. This study aimed to observe the estradiol levels in breast cancer patients before and after chemotherapy.

36895998

Nephrolithiasis-Associated Renal Cell Carcinoma in Patients Who Underwent Nephrectomy: A Single-Center Experience.

Kidney stones (nephrolithiasis) affect around 5% of the world's population. Some medical disorders, like obesity or diabetes, have increased the incidence and prevalence of nephrolithiasis. In addition, chronic inflammation and infection are frequently linked to kidney stone formation. Urothelial cell proliferation may change as a result of chronic inflammation, tumors will therefore develop as a result of this. The correlation between nephrolithiasis and renal cell cancer can also be explained by shared risk factors. At Adam Malik General Hospital, we strive to identify the risk factor for stone-induced renal cell cancer.

36895999

Cutaneous Malignant Melanoma Presenting as an Isolated Splenic Metastasis: An Update.

Although the spleen is a highly vascularized organ, metastatic deposits from non-hematolymphoid solid malignancies are rare. This is reasoned to the inherent resistance of the splenic parenchyma to harbor metastases. The splenic capsule, lack of afferent lymphatics, contractile properties of the spleen, and the angular and gyroid course of the splenic artery form several barriers against the metastatic spread of malignant tumors. Moreover, the immune cells in the white and red pulps of the spleen have strong defensive ability against the tumor cells. Metastasis from solid tumors to the spleen often occurs only during widespread distant spread. Malignant melanoma is a rare but fatal malignancy. Isolated splenic metastasis from malignant melanoma is exceptionally rare. Studies that addressed the splenic metastasis from cutaneous malignant melanoma are scarce. This minireview was performed to address this subject. Here we present an overview of the clinicopathologic features of isolated splenic metastatic melanoma. The diagnostic biochemical markers in melanoma are also discussed.

36896000

Real-World Experience of Adults With Acute Myeloid Leukemia on Hypomethylating Agents With or Without Venetoclax at a Comprehensive Cancer Center.

Venetoclax (VEN) bination with hypomethylating agent (HMA) therapy is a standard treatment option for patients with newly diagnosed acute myeloid leukemia (AML); however, data are limited in the relapsed or refractory (R/R) populations and in those with poor-risk disease. A retrospective review was conducted involving patients with AML who received HMA alone or bination with VEN (VEN + HMA).

36896001

Uses of Vascular Endothelial Growth Factor C as a Lung Adenocarcinoma Prognostic Biomarker.

Lung adenocarcinoma (LUAD) is the mon type of lung cancer and a leading cause of death worldwide. Vascular endothelial growth factor C (VEGF-C) has been identified as a prognosis prediction marker for LUAD. However, VEGF-C protein expression does not appear to significantly relate to LUAD patient survival in several studies.

36896002

Adult Primary Retroperitoneal Lymphangioma: Updated Facts.

Lymphangioma is a rare, benign tumor of the lymphatic system. It is believed to be a congenital malformation, when part of the lymphatic channels fail to connect to the main lymphatic system. Lymphangioma is a tumor of the pediatric age, with 50% of patients presenting at birth. The head and neck are the main affected sites (75%), while the retroperitoneal cavity is the least affected area, prises less than 1% of cases. Adult lymphangioma is an extremely rare tumor, and adult retroperitoneal lymphangioma (ARL) is even a rarer tumor. Over the last two decades, we have experienced a significant increase in reports published in the English literature discussing ARL. As reports have increased, several questions about previously known facts regarding this tumor arose: For years, it was known that ARL is usually an asymptomatic tumor which is incidentally found - is it a true claim? Is abdominal magnetic resonance imaging the radiological test of choice for diagnosis? What is the best therapeutic option? The main aim for this article is to review the current and old English literature concerning ARL, in order to collect data regarding demographic features, clinical presentation, imaging tests used for diagnosis, therapeutic options and follow-up. This in turn will give precise updated answers for the previous questions. In addition, it will raise awareness for the treating physician regarding the most effective approach for early diagnosis and best therapeutic option to be selected.

36896004

Tackling diabetic foot: limb salvage during the COVID-19 pandemic.

Lower extremity amputation resulting from diabetic foot ulcer, with neuropathic and/or ischemic etiologies, remains a devastating and plication of diabetes mellitus. This study evaluated changes in care delivery of diabetic foot ulcer patients during the COVID-19 pandemic. A longitudinal assessment evaluating the ratio of major lower extremity amputation to minor lower extremity amputations after implementation of novel strategies bat access restrictions pared to the pre-COVID-19 era.

36896003

Differential associations of leisure music engagement with resilience: A network analysis.

Several factors associated with resilience as the maintenance of mental health despite stress exposure can be strengthened through participation in leisure time activities. Since many people listen to or make music in their leisure time, the aim of the present study was to provide insights into the architecture of how resilience relates to passive and active music engagement.

36896007

m6A methylation: Critical roles in aging and neurological diseases.

N6-methyladenosine (m6A) is the most abundant internal RNA modification in eukaryotic cells, which participates in the functional regulation of various biological processes. It regulates the expression of targeted genes by affecting RNA translocation, alternative splicing, maturation, stability, and degradation. As recent evidence shows, of all organs, brain has the highest abundance of m6A methylation of RNAs, which indicates its regulating role in central nervous system (CNS) development and the remodeling of the cerebrovascular system. Recent studies have shown that altered m6A levels are crucial in the aging process and the onset and progression of age-related diseases. Considering that the incidence of cerebrovascular and degenerative neurologic diseases increase with aging, the importance of m6A in neurological manifestations cannot be ignored. In this manuscript, we focus on the role of m6A methylation in aging and neurological manifestations, hoping to provide a new direction for the molecular mechanism and novel therapeutic targets.

36896008

The function of Golgi apparatus in LRRK2-associated Parkinson's disease.

Parkinson's disease (PD) is a chronic neurodegenerative disease associated with the intracellular organelles. Leucine-rich repeat kinase 2 (LRRK2) is a large multi-structural domain protein, and mutation in LRRK2 is associated with PD. LRRK2 regulates intracellular vesicle transport and function of organelles, including Golgi and lysosome. LRRK2 phosphorylates a group of Rab GTPases, including Rab29, Rab8, and Rab10. Rab29 acts in mon pathway with LRRK2. Rab29 has been shown to recruit LRRK2 to the plex (GC) to stimulate LRRK2 activity and alter the Golgi apparatus (GA). Interaction between LRRK2 and Vacuolar protein sorting protein 52 (VPS52), a subunit of the Golgi-associated retrograde protein plex, mediates the function of intracellular soma trans-Golgi network (TGN) transport. VPS52 also interacts with Rab29. Knockdown of VPS52 leads to the loss of LRRK2/Rab29 transported to the TGN. Rab29, LRRK2, and VPS52 work together to regulate functions of the GA, which is associated with PD. We highlight recent advances in the roles of LRRK2, Rabs, VPS52, and other molecules, such as Cyclin-dependent kinase 5 (CDK5) and protein kinase C (PKC) in the GA, and discuss their possible association with the pathological mechanisms of PD.

36896009

Effect of pretreatment strategies on halophyte

Bioethanol is believed to be an influential revolutionary gift of biotechnology, owing to its elevating global demand and massive production. Pakistan is home to a rich diversity of halophytic flora, convertible into bounteous volumes of bioethanol. On the other hand, the accessibility to the cellulosic part of biomass is a major bottleneck in the successful application of biorefinery processes. The mon pre-treatment procedures existent include physicochemical and chemical approaches, which are not environmentally benign. To e these problems, biological pre-treatment has gained importance but the drawback is the low yield of the extracted monosaccharides. The current research was aimed at exploring the best pre-treatment method for the bioconversion of halophyte

36896010

Comparison between articular chondrocytes and mesenchymal stromal cells for the production of articular cartilage implants.

Focal lesions of articular cartilage give rise to pain and reduced joint function and may, if left untreated, lead to osteoarthritis. Implantation of

36896011

Actuation and design innovations in earthworm-inspired soft robots: A review.

Currently, soft robotics technologies are creating the means of robotic abilities and are required for the development of biomimetic robotics. In recent years, earthworm-inspired soft robot has garnered increasing attention as a major branch of bionic robots. The major studies on earthworm-inspired soft robots focuses on the deformation of the earthworm body segment. Consequently, various actuation methods have been proposed to conduct the expansion and contraction of the robot's segments for otion simulation. This review article aims to act as a reference guide for researchers interested in the field of earthworm-inspired soft robot, and to present the current state of research, summarize current design pare the advantages and disadvantages of different actuation methods with the purpose of inspiring future innovative orientations for researchers. Herein, earthworm-inspired soft robots are classified into single- and multi-segment types, and the characteristics of various actuation methods are introduced pared according to the number of matching segments. Moreover, various promising application instances of the different actuation methods are detailed along with their main features. Finally, motion performances of the robots pared by two normalized pared by body length and pared by body diameter, and future developments in this research direction are presented.

36896012

Zwitterionic poly(sulfobetaine methacrylate)-based hydrogel coating for drinking water distribution systems to inhibit adhesion of waterborne bacteria.

Presence of biofilms in drinking water distribution systems (DWDS) can be a nuisance, leading to several operational and maintenance issues (i.e., increased secondary disinfectants demand, pipe damage or increased flow resistance), and so far, no single control practice was found to be sufficiently effective. Here, we propose poly (sulfobetaine methacrylate) (P(SBMA))-based hydrogel coating application as a biofilm control strategy in DWDS. The P(SBMA) coating was synthetized through photoinitiated free radical polymerization on polydimethylsiloxane with binations of SBMA as a monomer, and

36896013

Extracellular vesicles secreted by human gingival mesenchymal stem cells promote bone regeneration in rat femoral bone defects.

Extracellular vesicles (EVs), ponents of paracrine secretion, are involved in various pathological and physiological processes of the body. In this study, we researched the benefits of EVs secreted by human gingival mesenchymal stem cells (hGMSC-derived EVs) in promoting bone regeneration, thereby providing new ideas for EVs-based bone regeneration therapy. Here, we successfully demonstrated that hGMSC-derived EVs could enhance the osteogenic ability of rat bone marrow mesenchymal stem cells and the angiogenic capability of human umbilical vein endothelial cells. Then, femoral defect rat models were created and treated with phosphate-buffered saline, nanohydroxyapatite/collagen (nHAC), a grouping of nHAC/hGMSCs, and a grouping of nHAC/EVs. The results of our study indicated that bination of hGMSC-derived EVs and nHAC materials could significantly promote new bone formation and neovascularization with a similar effect to that of the nHAC/hGMSCs group. Our es provide new messages on the role of hGMSC-derived EVs in tissue engineering, which exhibit great potential in bone regeneration treatment.

36896015

Exploring Class I polyhydroxyalkanoate synthases with broad substrate specificity for polymerization of structurally diverse monomer units.

Polyhydroxyalkanoate (PHA) synthases (PhaCs) are key enzymes in PHA polymerization. PhaCs with broad substrate specificity are attractive for synthesizing structurally diverse PHAs. In the PHA family, 3-hydroxybutyrate (3HB)-based copolymers are industrially produced using Class I PhaCs and can be used as practical biodegradable thermoplastics. However, Class I PhaCs with broad substrate specificities are scarce, prompting our search for novel PhaCs. In this study, four new PhaCs from the bacteria

36896016

Metabolic engineering of

Lactate is the precursor for polylactide. In this study, a lactate producer of

36896017

Emergency physician professionalism versus wellness: A conceptual model.

Striking the balance between professional duties, obligations, and responsibility with protecting one's wellness as a physician and as an individual have been brought into sharper focus during COVID-19. The objective of this paper is to describe ethical principles in the balance between emergency physician wellness and professional responsibility to patients and the public. We propose a schematic that helps us as emergency physicians visualize continuously striving to be both well and professional.

36896019

Designing clinical guidelines that improve access and satisfaction in the emergency department.

Clinical guidelines are evidence-based clinician decision-support tools that improve health es, reduce patient harm, and decrease healthcare costs, but are often underused in emergency departments (EDs). This article describes a replicable, evidence-based design-thinking approach to developing best practices for guideline design that improves clinical satisfaction and usage. We used a 5-step process to enhance guideline usability in our ED. First, we conducted end-user interviews to identify barriers to guideline usage. Second, we reviewed the literature to identify key principles in guideline design. Third, we applied our findings to create a standardized guideline format, incorporating rapid cycle learning and iterative improvements. Fourth, we ensured the clinical validity of our updated guidelines by using a rigorous process for peer review. Lastly, we evaluated the impact of our guideline conversion process by tracking clinical guidelines access per day from October 2020 to January 2022. Our end-user interviews and review of the design literature revealed several barriers to guideline use, including lack of readability, design inconsistencies, and plexity. Although our previous clinical guideline system averaged 0.13 users per day, >43 users per day accessed the clinical guidelines on our new digital platform in January 2022, representing an increase in access and use exceeding 33,000%. Our replicable process using open-access resources increased clinician access to and satisfaction with clinical guidelines in our ED. Design-thinking and use of low-cost technology can significantly improve clinical guideline visibility and has the potential to increase guideline use.