Miracle-dz/UniFAR-FTUs huggingface dataset:
Prognostic and Predictive Value of Circulating Inflammation Signature in Non-Metastatic Nasopharyngeal Carcinoma: Potential Role for Individualized Induction Chemotherapy

Purpose We sought to assess the prognostic and predictive value of a circulating inflammation signature (CISIG) and develop CISIG-based tools for predicting prognosis and guiding individualized induction chemotherapy (ICT) in non-metastatic nasopharyngeal carcinoma (NPC). Patients and Methods We retrospectively collected a candidate inflammatory biomarker panel from patients with NPC treated with definitive radiotherapy between 2012 and 2017. We developed the CISIG using candidate biomarkers identified by a least absolute shrinkage and selection operator (LASSO) Cox regression model. The Cox regression analyses were used to evaluate the CISIG prognostic value. A CISIG-based prediction model was constructed, validated, and assessed. Potential stratified ICT treatment effects were examined. Results A total of 1149 patients were analyzed. Nine biomarkers selected by LASSO regression in the training cohort were used to construct the CISIG, including hyaluronidase, laminin, procollagen III, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, high-density lipoprotein, lactate dehydrogenase, and C-reactive protein-to-albumin ratio. CISIG was an independent prognostic factor for disease-free survival (DFS; hazard ratio: 2.65, 95% confidence interval: 1.93–3.64; P < 0.001). High CISIG group (>−0.2) was associated with worse 3-year DFS than low CISIG group in both the training (67.5% vs 88.3%, P < 0.001) and validation cohorts (72.3% vs 85.1%, P < 0.001). We constructed and validated a CISIG-based nomogram, which showed better performance than the clinical stage and Epstein–Barr virus DNA classification methods. A significant interaction between CISIG and the ICT treatment effect was observed (P for interaction = 0.036). Patients with high CISIG values did not benefit from ICT, whereas patients with low CISIG values significantly benefited from ICT. Conclusion The developed CISIG, based on a circulating inflammatory biomarker panel, adds prognostic information for patients with NPC. The proposed CISIG-based tools offer individualized risk estimation to facilitate suitable ICT candidate identification.
Successful Management of a Patient with Refractory Primary Central Nervous System Lymphoma by Zanubrutinib

Abstract Primary central nervous system lymphoma (PCNSL) is a rare subtype of extranodal non-Hodgkin lymphoma, and the most frequent histological type is diffuse large B‐cell lymphoma (DLBCL). Bruton’s tyrosine kinase inhibitor (BTKi) has shown clinical activity in DLBCL. We herein report a 53-year-old man who presented with binocular diplopia, gait instability, dizziness and bucking. He was diagnosed with PCNSL by cranial magnetic resonance imaging (MRI) scan and brain biopsy. Next-generation sequencing (NGS) examination identified multiple genetic abnormalities. The patient was started on a high-dose methotrexate (HD-MTX)-based protocol for two courses. However, the patient developed disease progression. The patient’s phenotypic and genetic characteristics strongly suggested BN2-DLBCL, and zanubrutinib was added to the subsequent chemotherapy regimen. The treatment was well tolerated, and complete remission (CR) was achieved after three courses of chemotherapy with the new regimen. The patient then received autologous hematopoietic stem cell transplantation after four courses of chemotherapy with the new regimen. MRI revealed stable CR. Here, we report a successful case of refractory PCNSL treated with zanubrutinib. Small molecules, such as zanubrutinib, may be selectively integrated into first-line regimens of PCNSL to enhance curative effect and reduce recurrence.
HLA complex group 11 is involved in colorectal carcinoma cisplatin resistance via the miR-214-5p/SOX4 axis

The aim of the present study was to investigate the roles and potential mechanisms of long non-coding RNA HLA complex group 11 (HCG11) in colorectal carcinoma. Reverse transcription-quantitative PCR was used to detect HCG11 expression in clinical tissues and survival analysis was performed to identify its prognostic value. In order to investigate its specific biological functions in colorectal carcinoma, the transfection technique was used for the knockdown and overexpression of HCG11. Dual-luciferase reporter gene and RNA pull-down assays were used to identify the binding association between HCG11 and microRNA (miR)-214-5p. Western blot analysis was used to detect the mechanism of epithelial-mesenchymal transition (EMT) regulation in tumor cells in the pathway downstream of HCG11. HCG11 level was high in colorectal carcinoma tissues, which was associated with poor patient prognosis; however, chemotherapy may prevent the upregulation of HCG11 in colorectal carcinoma. HCG11-knockdown suppressed the proliferation, migration and chemotherapeutic sensitivity of colorectal carcinoma cells, whereas HCG11-overexpression enhanced chemotherapeutic sensitivity. miR-214-5p was revealed to be a target gene, and upon direct interaction, a negative regulator of HCG11 in colorectal carcinoma cells. Inhibition of miR-214-5p reversed the restriction of HCG11 on the malignant activity of colorectal carcinoma cells, while miR-214-5p mediated the chemotherapy-related intracellular EMT pathway. In conclusion, HCG11 is a vital oncogene of colorectal carcinoma involved in mediating the chemotherapeutic resistance of tumors.
Peripheral and Central Pathological Mechanisms of Chronic Low Back Pain: A Narrative Review

Abstract Chronic low back pain (CLBP), lasting >3 months, is the end result of multiple pathogenic factors. Unfortunately, little is known about CLBP pathogenesis, which limits its advancements in clinical therapy and disease management. This paper summarizes the known pathological axes of CLBP, involving both peripheral and central systems. In particular, this paper details injurious nerve stimulation, inflammation-induced peripheral pathway, and central sensitization. Lumbar components, such as intervertebral disc (IVD), facet joints, muscles, fascia, ligaments, and joint capsules, contain pain receptors called nociceptors. Degeneration of the aforementioned lumbar components activates inflammatory pathways, which can directly damage nerves, lower nociceptor threshold to fire action potentials (AP), and cause pain. Additionally, damaged lumbar IVDs and endplates can also lead to the pathologic invasion of nerve growth and innervation, followed by the compression of herniated IVDs on nerve roots, thereby causing traumatic neuropathic pain. The central mechanism of CLBP involves alteration of the sensory processing of the brain and malfunction of the descending pain modulatory system, which facilitates pain amplification in the center nervous system (CNS). Lastly, abnormalities in the brain biochemical metabolism, activation of glial cells, and subsequent inflammation also play important roles in CLBP development. Taken together, inflammation plays an important role in both peripheral and central sensitization of CLBP. Due to the heterogeneity of CLBP, its pathological mechanism remains complex and difficult to understand. Therefore, it is a worthy field for future research into the subcomponents of CLBP pathogenesis, in order to distinguish the specific form of the disease, identify its origins, and develop corresponding highly effective comprehensive therapy against CLBP.
Preparation, Biocompatibility and Antitumor Activity of Nanodelivery System Targeting Breast Cancer Base on a Silica Nanoparticle

Background Breast cancer (BC) is the most common type of cancer among women worldwide, and about 30% of males will have recurrent disease. Methods In order to treat recurrent BC, we designed a type of silica nanodelivery system loaded with epirubicin and curcumin (composite nanoparticles, CNPs). To promote CNPs clinical application, the stability, the blood, immune and cell compatibility, skin stimulation experiments, anti-tumor activity in vivo and in vitro were studied. Results In our study, the CNPs had a particle size of 73.9 nm and a uniform size and morphology; moreover, they maintained physical and chemical stability in the blood protein environment. Additionally, results showed that nanoparticles had good blood and immune compatibility, and they did not affect intracellular superoxide dismutase (SOD) and intracellular catalase (CAT). Skin stimulation experiments showed that CNPs did not cause any obvious irritative damage to the intact skin of rabbits. In the cytotoxicity study, CNPs showed strongest antitumor activity. The results of cell cycle and apoptosis studies showed that CNPs could mainly induce apoptosis of S and G2/M phase cells. In vivo, CNPs showed strongest aggregation in the tumor after 6 h of tail vein administration, and a large amount of CNPs continued to accumulate in the blood after 12 h of administration, indicating that CNPs had long circulation ability. The in vivo antitumor activities showed that CNPs had the strongest antitumor activity and tumor targeting ability, and hematoxylin-eosin staining of internal organs showed no obvious difference between treatment groups and negative control. Conclusion CNPs have an ideal biosafety and therapeutic effect for recurrent BC, and they have potential clinical application value.
Setting Measurement-Based Care in Motion: Practical Lessons in the Implementation and Integration of Measurement-Based Care in Psychiatry Clinical Practice

Abstract Measurement-based care (MBC) involves the systematic use of standardized measurements to inform treatment decisions. MBC can enhance clinical decision-making and quality of care by prompting personalized changes in treatment based on measured patient outcomes. MBC can also promote more precise communications between patients and clinicians around individual patient care. While commonly employed in psychiatric clinical research, the use of MBC in everyday practice can be complicated by clinic operations and variability across patients. We implemented MBC in the UT Southwestern Psychiatry Multispecialty Outpatient Clinic during the expansion of our general psychiatry clinic and subspecialty targeted programs. This article describes the top 10 lessons we learned as we confronted practical obstacles around implementing the ideals of MBC into a pre-existing, busy psychiatric clinical practice and how doing so impacts care, provider engagement, patient engagement, and research opportunity.
Angiotensin System Polymorphisms’ in SARS-CoV-2 Positive Patients: Assessment Between Symptomatic and Asymptomatic Patients: A Pilot Study

Introduction The renin–angiotensin–aldosterone system (RAAS), a metabolic cascade regulating pressure and circulating blood volume, has been considered the main system involved in the pathogenesis of severe lung injury and organs decline in COVID-19 patients. The angiotensin I-converting enzyme (ACE1), angiotensin-converting enzyme 2 (ACE2), angiotensinogen (AGT) and receptors angiotensin II receptor type 1 (AGTR1) are key factors for SARS-CoV-2 entering in the cells, sodium and water retention with an increase blood pressure, promotion of fibrotic and inflammatory phenomena resulting in a cytokine storm. Methods In this pilot study, the frequencies of six polymorphisms in the ACE1, ACE2, AGT and AGTR1 genes were analysed in symptomatic patients affected by COVID-19 and compared with the results obtained from asymptomatic subjects. Results Thus, we have identified that rs2074192 (ACE2), rs1799752 (ACE1) and rs699 (AGT) SNPs could potentially be a valuable tool for predicting the clinical outcome of SARS-CoV-2 infected patients. A genetic predisposition may be prospected for severe internal organ damages and poor prognosis in patients with COVID-19 disease, as observed in symptomatic vs asymptomatic. Conclusion This study provides evidence that analysis of RAAS polymorphisms could be considered the key point in understanding and predicting the SARS-CoV-2 course infection.
Immune-related gene expression signatures in colorectal cancer

The immune system is crucial in regulating colorectal cancer (CRC) tumorigenesis. Identification of immune-related transcriptomic signatures derived from the peripheral blood of patients with CRC would provide insights into CRC pathogenesis, and suggest novel clues to potential immunotherapy strategies for the disease. The present study collected blood samples from 59 patients with CRC and 62 healthy control patients and performed whole blood gene expression profiling using microarray hybridization. Immune-related gene expression signatures for CRC were identified from immune gene datasets, and an algorithmic predictive model was constructed for distinguishing CRC from controls. Model performance was characterized using an area under the receiver operating characteristic curve (ROC AUC). Functional categories for CRC-specific gene expression signatures were determined using gene set enrichment analyses. A Kaplan-Meier plotter survival analysis was also performed for CRC-specific immune genes in order to characterize the association between gene expression and CRC prognosis. The present study identified five CRC-specific immune genes [protein phosphatase 3 regulatory subunit Bα (PPP3R1), amyloid β precursor protein, cathepsin H, proteasome activator subunit 4 and DEAD-Box Helicase 3 X-Linked]. A predictive model based on this five-gene panel showed good discriminatory power (independent test set sensitivity, 83.3%; specificity, 94.7%, accuracy, 89.2%; ROC AUC, 0.96). The candidate genes were involved in pathways associated with ‘adaptive immune responses’, ‘innate immune responses’ and ‘cytokine signaling’. The survival analysis found that a high level of PPP3R1 expression was associated with a poor CRC prognosis. The present study identified five CRC-specific immune genes that were potential diagnostic biomarkers for CRC. The biological function analysis indicated a close association between CRC pathogenesis and the immune system, and may reveal more information about the immunogenic and pathogenic mechanisms driving CRC in the future. Overall, the association between PPP3R1 expression and survival of patients with CRC revealed potential new targets for CRC immunotherapy.
Prevalence, Causes, and Factors Associated with Visual Impairment in a Chinese Elderly Population: The Rugao Longevity and Aging Study

Purpose This study aimed to explore the current prevalence, causes, and factors associated with visual impairment in a Chinese elderly population. Methods A random sample of 2164 candidates aged ≥70 years was selected. Among them, 1914 participants (response rate: 88.4%) underwent comprehensive eye examinations. The prevalence and causes of visual impairment were estimated, and the associated factors were identified. Results The standardized prevalence of mild visual impairment (<6/12 to ≥6/18), moderate to severe visual impairment (MSVI) (<6/18 to ≥3/60), and blindness (<3/60) in the better eye were 20.5%, 25.8%, and 3.4%, respectively. The leading cause of visual impairment was cataract (49.7%), followed by uncorrected refractive error (26.5%), myopic maculopathy (5.8%), and posterior capsular opacification (5.5%). Optical coherence tomography revealed that vitreoretinal interface abnormalities were the third most common cause of monocular mild visual impairment (2.2%) and MSVI (4.4%) in the elderly population. A large number of patients with visual impairment (81.7%) were amenable to undergo the interventions. Visual impairment was associated with advanced age (odds ratio [OR], 1.09 per year; p<0.001), female sex (OR, 1.59; p=0.003), self-reported visual impairment (OR, 1.91; p<0.001), cognitive impairment (OR, 1.40, p=0.005), and high educational level (OR, 0.75; primary, p=0.045; and OR, 0.53, secondary or higher; p<0.001). Conclusion Visual impairment was common in the Chinese elderly population and a severe health and social problem. Practicable policies are urgently needed to popularize eye health knowledge and promote treatments for visual impairment in elderly people in rural China.
Bidirectional genome-wide CRISPR screens reveal host factors regulating SARS-CoV-2, MERS-CoV and seasonal HCoVs

Several genome-wide CRISPR knockout screens have been conducted to identify host factors regulating SARS-CoV-2 replication, but the models used have often relied on overexpression of ACE2 receptor. Additionally, such screens have yet to identify the protease TMPRSS2, known to be important for viral entry at the plasma membrane. Here, we conducted a meta-analysis of these screens and showed a high level of cell-type specificity of the identified hits, arguing for the necessity of additional models to uncover the full landscape of SARS-CoV-2 host factors. We performed genome-wide knockout and activation CRISPR screens in Calu-3 lung epithelial cells, as well as knockout screens in Caco-2 intestinal cells. In addition to identifying ACE2 and TMPRSS2 as top hits, our study reveals a series of so far unidentified and critical host-dependency factors, including the Adaptins AP1G1 and AP1B1 and the flippase ATP8B1. Moreover, new anti-SARS-CoV-2 proteins with potent activity, including several membrane-associated Mucins, IL6R, and CD44 were identified. We further observed that these genes mostly acted at the critical step of viral entry, with the notable exception of ATP8B1, the knockout of which prevented late stages of viral replication. Exploring the pro- and anti-viral breadth of these genes using highly pathogenic MERS-CoV, seasonal HCoV-NL63 and −229E and influenza A orthomyxovirus, we reveal that some genes such as AP1G1 and ATP8B1 are general coronavirus cofactors. In contrast, Mucins recapitulated their known role as a general antiviral defense mechanism. These results demonstrate the value of considering multiple cell models and perturbational modalities for understanding SARS-CoV-2 replication and provide a list of potential new targets for therapeutic interventions.
Fidelity of Information Processing on a Psychomotor Vigilance Task Predicts Changes in Self-Reported Sleepiness Ratings

Introduction Daytime sleepiness is a common problem. Although sleepiness is primarily assessed at the self-report unit of analysis, factors that contribute to an individual’s experience and report of sleepiness remain poorly understood. While sleepiness is known to impact vigilance performance, the impact of vigilance performance on sleepiness reports is less well understood. We aimed to explore how performance on a psychomotor vigilance task (PVT) relates to changes in self-reported sleepiness in a rested condition. Methods Participants were 66 adults (Mdn=23, range 18–49 years old), 47% female, 88% white, with a wide range of insomnia symptoms. Participants rated their sleepiness on a scale from 1 (not sleepy) to 10 (extremely sleepy) at the start (pre) and the end (post) of a 10-minute computerized PVT. Ordinal regression determined whether mean reciprocal reaction time, a measure of overall performance, or the log-transformed signal-to-noise ratio (LSNR), a measure of fidelity of information processing, predicted post-sleepiness, adjusting for pre-sleepiness, insomnia, and potential confounds. Results Lower LSNR predicted greater change in sleepiness (pre-to-post PVT) and higher post-sleepiness even after adjusting for pre-sleepiness, mean reciprocal reaction time, insomnia, and other potential confounds (p<0.05). Discussion When adjusting for insomnia symptoms and potential confounds, participants with lower fidelity of information processing reported higher sleepiness than they had reported at the start of the PVT. Possible mechanisms and explanations are discussed in relation to a 3-factor model of sleep-wake states. This line of research may contribute to innovative approaches to assessing and treating sleepiness.
Success of Primary Trabeculectomy in Advanced Open Angle Glaucoma

Aim The study assesed trabeculectomy survival in advanced open angle glaucoma (OAG). Methods This is a retrospective longitudinal study in advanced OAG undergoing primary trabeculectomy. Clinical and demographic parameters were recorded. Surgical survival (qualified/complete) was calculated by Kaplan–Meier analysis for multiple upper limits of intraocular pressure (IOP) with/without medication (≤21 mmHg, ≤18 mmHg, ≤15 mmHg, ≤12 mmHg); Cox hazard ratio analysis identified parameters influencing survival. Results We included 165 eyes from 165 OAG patients: primary forms (POAG) – 86 eyes and secondary (pseudoexfoliative, SOAG) – 79 eyes; mean follow-up interval was 36.21 ± 13.49 months. Clinical parameters were comparable between sub-groups at baseline, except a higher IOP in SOAG vs POAG (36.6 ± 13.2 vs 32.7 ± 11.1 mmHg, p = 0.04); IOP reduction was similar (SOAG vs POAG) 53.93% vs 56.19%, p = 0.45, yet longer hospitalization (8.47 ± 4.39 (SOAG) vs 6.69 ± 3.01 days (POAG), p=0.03) and more medications (0.65 ± 0.24 vs 0.36 ± 0.16, p = 0.05) were needed to achieve comparable final IOP (16.0 ± 9.1 vs 15.1 ± 7.8 mmHg, p = 0.45). Kaplan Meier survival analysis applied for IOP ≤21 mmHg, ≤18 mmHg, ≤15 mmHg and ≤12 mmHg, revealed complete success in 26.2%, 27.3%, 34.5% and 54.6% eyes, respectively; qualified success was found in 45.7%, 48.6%, 77% and 88.6% eyes, respectively. Multiple medications at baseline diminished survival in all tested models (hazard ratio HR > 1, p<0.05), while 5FU+needling improved survival, mostly if combined with lower IOP regime: HR = 0.15, 95% CI = [0.07 −1.12], p = 0.06, if IOP ≤15 mmHg and HR = 0.09, 95% CI = [0.02–1.25], p = 0.06, if IOP ≤12 mmHg. Conclusion Trabeculectomy in advanced OAG reached very good survival rates (77% and 88.6%) at 36 months postoperative, if IOP could be maintained ≤15 mmHg, respectively ≤12 mmHg with medication and additional needling+5FU maneuvers. Specific factors influencing survival were identified for each success definition.
Cell Adhesion Molecules are Upregulated and May Drive Inflammation in Chronic Rhinosinusitis with Nasal Polyposis

Purpose Chronic rhinosinusitis with nasal polyps (CRSwNP) is predominantly characterized by eosinophil- and T helper 2 cell (Th2)-biased inflammation. Integrins and intercellular adhesion molecules (ICAMs) are superfamilies of cell adhesion molecules (CAMs) that facilitate the recruitment and trafficking of immune cells and have been implicated in coordinating eosinophil and Th2 cell adhesion and signaling in asthma. The roles of CAMs in CRSwNP, however, remain poorly understood. The purpose of this study was to characterize the systemic and local expression of CAMs and identify which CAMs are potentially involved in CRSwNP pathology. Materials and Methods A prospective observational study was conducted using peripheral blood and anterior ethmoid tissues of patients with CRSwNP (n=32) and controls (n=15). Multiplex gene analysis and Pearson correlations were performed to identify associations between systemically and locally expressed CAMs. Based on the gene expression results, immunohistochemical evaluation and quantification of cells expressing integrins ITGAM, ITGAX, and ITGB2, as well as ICAM-3 in sinonasal tissues were conducted to compare local protein expression patterns. Results Integrin and ICAM genes were significantly elevated in the blood (p<0.001 to p<0.05) and sinuses (p<0.0003 to p<0.05) of patients with CRSwNP compared to controls. Strong positive correlations of genes expressed in the blood (p<0.01 to p<0.05) and sinuses (p<0.01) were observed between ITGAM, ITGAX, ITGB2, and ICAM3. ITGAM-, ITGB2-, ICAM-3-, and ICAM-3/ITGB2-positive cell counts were significantly increased in CRSwNP compared to controls (p<0.0001 to p<0.04), and a positive correlation between ICAM-3/ITGB2- and ITGAM-positive cell counts was observed (p<0.02). Conclusion The systemic and local expression of ITGAM, ITGB2, and ICAM-3 is significantly upregulated in CRSwNP, suggesting that integrin complex ITGAM/ITGB2 and ICAM-3 serve a potential role in inflammation-mediated signaling in CRSwNP.