Miracle-dz/UniFAR-FTUs huggingface dataset:
Siglecs, Novel Immunotherapy Targets, Potentially Enhance The Effectiveness of Existing Immune Checkpoint Inhibitors in Glioma Immunotherapy

Background Inhibitors of immune checkpoints have shown little effect in clinical trials involving glioma patients. Here, we explored novel targets for use in future treatments. Previous studies showed the sialic acid-binding Ig-like lectin (Siglec) family to have a specific role in immunosuppression. We aimed to study the characteristics and immune function of Siglec family members. Methods Transcriptome data from 1024 glioma samples and 1551 glioma single cells were used in our study. Clinical and molecular pathology information was also included. Statistical, bioinformatical methods, and single-cell sequencing analysis were applied to investigate the role of Siglec family members. Results Siglecs-5, −7, −9, and −16 showed a significant correlation with immunosuppression in glioma. They are typically expressed in higher grade, IDH-wildtype, and mesenchymal subtype gliomas. Siglec-5, −7, and −9 had a similar immune function to TIM-3, while Siglec-16 was similar to PD-L1, suppressing tumor immunity via different mechanisms. Joint use of Siglec-inhibitors and immune checkpoint inhibitors could prolong the survival of glioma patients. Conclusion Siglec-5, −7, −9, and −16 suppressed tumor immunity in different ways. Joint usage of inhibitors may be an effective means to improve the efficacy of glioma immunotherapy.
Oral Health Status And Treatment Needs Among Apple Farm Workers In Shimla (Rural)

Introduction: Fruits like apples and pears, blueberries, mango, cantaloupe, and banana are all fibrous in nature, but among them apples have been regarded as nature's toothbrush. They are assumed to be good for dental health as they have condensed tannins that may help prevent periodontal or gum disease . These seasonal fruits are picked by the farmers, who remain one of the most economically disadvantaged working people. Inspite of this, they might have good oral hygiene, due to the fact they consume a lot of apples during the picking season. Objective: The objective of the study was to assess the oral health status and treatment needs of apple orchard workers in Shimla District (Rural) Methodology: Data was collected from 900 farmers, working in the apple orchards, by using a specially prepared proforma, WHO 1997 'Oral health Assessment Form' and Silness and Loe plaque index. Result: Subjects with bleeding, calculus were 6.6%; 65.4% respectively; subjects with shallow pockets (4-5mm) were 22.4% and with deep pockets (> 6mm) were 2.0%. The mean number of decayed permanent teeth per person was 5.01+ 3.31. The plaque score for this study population was 0.9. Conclusion: The findings of this study clearly indicate the relatively low prevalence of severe form of periodontal disease, high prevalence of dental caries. and good plaque score among this population.
Vagus Nerve Stimulation For Treatment Resistant Depression: Case Series Of Six Patients - Retrospective Efficacy And Safety Observation After One Year Follow Up

Objective One year observation and evaluation of the VNS (vagus nerve stimulation) efficacy and safety for patients with treatment resistant depression in Polish conditions. Methods An open label, uncontrolled and one center retrospective study of VNS therapy was implemented with stable pharmacotherapy in 6 patients with treatment resistant depression (TRD). For the first 3 months, only VNS parameters were altered but the pharmacological treatment was unchanged and in the following 9 months, medication and VNS dosing parameters were altered according to the clinical state of the patients. Results The baseline 24-item Hamilton Depression Rating Scale (HAMD-24) score averaged 24. Both response (>50% reduction in baseline scores) and remission rates after 3 months of treatment were only 40%. After 1 year of VNS therapy, the response rates increased to 86%. Most frequent side-effects were voice alteration (86% at 3 months of stimulation) and headaches (40%). Conclusion VNS treatment was safe and effective in TRD patients and its efficacy increased with time. Efficacy ratings are similar to the previously reported studies using a congenial protocol.
Pain And The Use Of Gabapentinoids In German Nursing Home Residents - Results From An Analysis Based On Statutory Health Insurance Data

Background Gabapentinoids (gabapentin and pregabalin) are psychoactive medications that are increasingly used for different conditions. Since there is evidence that psychotropic drugs, in general, are often inappropriately prescribed in elderly patients, we aimed to determine frequency and indications of gabapentinoid prescribing for nursing home residents. Methods We analyzed data from a large German statutory health insurance database. Included were records from people ≥65 years-of-age, who were admitted to a nursing home between January 2010 and December 2014. We determined the number and proportion of common indications for on- and off-label prescriptions, the most frequent co-medications, and the characteristics of patients and prescribers. Results Of 127,277 residents, 9539 (7.5%) received gabapentinoids and 4852 initiated treatment (4.0%; with 66.3% pregabalin). Median age of gabapentinoid initiators was 84 years (78.5% females). In these users, on-label prescribing was found in 57.4%, predominantly for neuropathic pain. Other painful conditions were also chief causes (84.7%) for off-label prescribing. Gabapentinoids were mainly started by general practitioners (64.5%) while pain specialists contributed <2%. Forty-six percent of users received additional opioids and in 27.5% gabapentinoids were prescribed only once. Conclusion Gabapentinoids were frequently used in nursing home residents. Regular co-prescribing with opioids and psychotropic drugs might indicate employment to improve pain or assist treatment of conditions that are frequently associated with disruptive behavior such as dementia. However, more research is needed to better understand decision-making regarding gabapentinoid prescribing, especially in view of aggressive marketing, uncertain analgesic effects, problematic side effects, and uncritical use in the elderly.
Further Study of Circulating Antibodies to P16, CD25 and FOXP3 in Hepatocellular Carcinoma

Purpose It has been reported that circulating levels of IgG antibodies against p16, CD25 and FOXP3 proteins were significantly changed in patients with lung cancer, breast cancer and esophageal cancer. However, different peptide fragments appear to trigger different immune responses. This work aimed to analyze the alteration of plasma IgG for p16-derived peptide antigen called p16a, CD25-derived peptide antigen called CD25a and a FOXP3-derived antigen in hepatocellular carcinoma (HCC). Patients and methods An enzyme-linked immunosorbent assay (ELISA) was developed in-house to detect plasma IgG to p16a, CD25a and FOXP3 in 119 patients with HCC and 132 control subjects. Results Circulating levels of IgG antibodies for all three peptide antigens were significantly higher in HCC patients than control subjects (P<0.001 for all 3 assays); male patients mainly contributed to increase (P<0.01 for all 3 assays). Further analysis showed that plasma anti-p16a, anti-CD25a and anti-FOXP3 IgG levels were increased mainly in patients with intermediate and late-stage HCC (P<0.01 for both assays). Receiver operating characteristic (ROC) curve analysis showed that with a specificity of >95%, the area under the ROC curve (AUC) was 0.62 with 11.4% sensitivity for anti-p16a assay, 0.68 with 14.3% sensitivity for anti-CD25a IgG assay and 0.64 with 10.1% sensitivity for anti-FOXP3 assay. Of the three groups of HCC patients, group 3 (BCLC stage C+D) showed the best sensitivity for the detection of plasma anti-p16a and anti-FOXP3 IgG levels with an AUC of 0.66 and 0.65. Conclusion Circulating IgG antibody to p16a, CD25a and FOXP3 proteins may be a useful biomarker for assessment of HCC prognosis of this malignancy, especially in male patients with HCC.
Frequency-Specific Abnormalities Of Functional Homotopy In Alcohol Dependence: A Resting-State Functional Magnetic Resonance Imaging Study

Purpose Alcohol dependence (AD) is a relapsing mental disorder, typically occurring with concurrent tobacco misuse. Studies have reported disruption of the structural connectivity between hemispheres in the brain of individuals with AD. However, alterations in interhemispheric interactions and the specificity of frequency bands in individuals with AD remain unknown. Voxel-mirrored homotopic connectivity (VMHC) allows examination of functional interactions between mirrored interhemispheric voxels. Here, we use VMHC to investigate homotopic connectivity in AD and alcohol and nicotine co-dependence (AND) subjects. Patients and methods VMHC and seed-based functional connectivity (FC) in 24 AD, 30 AND, and 35 sex-, age-, and education-matched healthy control (HC) subjects were calculated for different frequency bands (slow-5, slow-4, and typical bands). Results Individuals with AD demonstrated significantly reduced VMHC in bilateral cerebellum posterior lobe (CPL) and increased VMHC in bilateral middle frontal gyrus (MFG) compared to that in HCs in the typical and slow-4 bands; higher VMHC in the MFG was positively correlated with the dependence-severity score. In all bands of the VMHC analysis, no significant differences were found between the AND and other groups. Subsequent seed-based FC analysis demonstrated all regions with abnormal VMHC exhibited altered FC with its counterpart in the contralateral hemisphere in the typical and slow-4 frequency bands. The FC value between bilateral CPL within AD subjects negatively correlated with alcohol intake. Conclusion Our findings provide further evidence of the role of disruptions within the brain circuitry supporting cognitive control in the development of AD. Alterations in neural activities in the CPL and MFG might be a biomarker of dependence severity in AD patients as assessed using clinical questionnaire and features. Because of the frequency specificity in VMHC, we must consider frequency effects in future AD functional magnetic resonance imaging studies.
PD-L1 Expression Is Regulated By NF-κB During EMT Signaling In Gastric Carcinoma

Purpose The aim of this study was to investigate the influence of epithelial-mesenchymal transition (EMT) occurring in gastric carcinoma cells and the involvement of programmed death ligand 1 (PD-L1) expression in tumor cells that undergo EMT. The mechanisms underlying PD-L1 expression during EMT in gastric carcinoma cells were also explored. Methods The capacities of migration and invasion were tested by cell scratch-wound assay and transwell chamber assay. PD-L1 expression by SGC7901 cell line and related mechanism were measured by Western blot and QRT-PCR. Results Treating with TGF-β1 promotes the motility of SGC7901 and PD-L1 expression in vitro, while activating the NF-κB signal pathway. Conclusion EMT increases the capacities of migration and invasion in gastric cancer cells, which resulted in up-regulation of PD-L1 expression via a mechanism that is dependent on NF-κB activation.
Respiratory Mechanics and Diaphragmatic Dysfunction in COPD Patients Who Failed Non-Invasive Mechanical Ventilation

Background Although non-invasive mechanical ventilation (NIV) is the gold standard treatment for patients with acute exacerbation of COPD (AECOPD) developing respiratory acidosis, failure rates still range from 5% to 40%. Recent studies have shown that the onset of severe diaphragmatic dysfunction (DD) during AECOPD increases risk of NIV failure and mortality in this subset of patients. Although the imbalance between the load and the contractile capacity of inspiratory muscles seems the main cause of AECOPD-induced hypercapnic respiratory failure, data regarding the influence of mechanical derangement on DD in this acute phase are lacking. With this study, we investigate the impact of respiratory mechanics on diaphragm function in AECOPD patients experiencing NIV failure. Methods Twelve AECOPD patients with respiratory acidosis admitted to the Respiratory ICU of the University Hospital of Modena from 2017 to 2018 undergoing mechanical ventilation (MV) due to NIV failure were enrolled. Static respiratory mechanics and end-expiratory lung volume (EELV) were measured after 30 mins of volume control mode MV. Subsequently, transdiaphragmatic pressure (Pdi) was calculated by means of a sniff maneuver (Pdisniff) after 30 mins of spontaneous breathing trial. Linear regression analysis and Pearson’s correlation coefficient served to assess associations. Results Average Pdisniff was 23.3 cmH2O (standard deviation 29 cmH2O) with 3 patients presenting bilateral diaphragm palsy. Pdisniff was directly correlated with static lung elastance (r=0.69, p=0.001) while inverse correlation was found with dynamic intrinsic PEEP (r=−0.73, p=0.007). No significant correlation was found with static intrinsic PEEP (r=−0.55, p=0.06), EELV (r=−0.4, p=0.3), airway resistance (r=−0.2, p=0.54), chest wall, and total elastance (r=−0-01, p=0.96 and r=0.3, p=0.36, respectively). Significant linear inverse correlation was found between Pdisniff and the ratio between Pdi assessed at tidal volume and Pdi sniff (r=−0.82, p=0.02). Conclusion The causes of extreme DD in AECOPD patients who experienced NIV failure might be predominantly mechanical, driven by a severe dynamic hyperinflation that overlaps on an elastic lung substrate favoring volume overload.
Computer Tomography (CT) Characteristics of Pulmonary Cystic Echinococcosis

Introduction: Cystic echinococcosis (CE) is a common zoonosis worldwide. The two most frequent location of CE are liver and lung. Confirmatory diagnosis of CE is routinely performed sung imaging methods such as computer aided tomography and nuclear magnetic resonance in humans. Aim: to investigate CT scan imaging of patients with pulmonary CE in Masih Daneshvari Hospital from 2011 to 2017. Matarial and Methods: This descriptive-analytic study was carried out on patients with pulmonary CE referring to Masih Daneshvari Hospital. By using the convenience sampling, 195 cases were selected from eligible patients. The data collection tool was a researcher-made questionnaire that included demographic, clinical and laboratory information. Data were analyzed using SPSS software version 20. Results: In this study, 84.1% and 15.9% of patients were diagnosed using surgical method and CT scan, respectively. Our findings indicated CE was most commonly located in liver (28.2%) and spleen was considered as the lowest location (3.1%). Furthermore, cough was the most common clinical symptom of patients. The lower right lobe opacity was found to be higher, while and Lingula was the least frequent. Conclusion: According to the findings of this study, surgery is the most important diagnostic and cough method as the most common clinical symptom of the disease. Since the CE with atypical symptoms is relatively common, physicians should always consider the lung CE in differential diagnosis of localized radiological images.
High hnRNP AB expression is associated with poor prognosis in patients with colorectal cancer

Heterogeneous ribonucleoprotein AB (hnRNP AB) is a member of the heterogeneous nuclear ribonucleoprotein family, which serves important functions in gene expression and signal transduction. However, the expression and clinicopathological significance of hnRNP AB in colorectal cancer (CRC) remain to be elucidated. To investigate the expression and clinical significance of hnRNP AB in CRC, hnRNP AB expression levels were analysed in two independent cohorts of patients with CRC. The results of reverse transcription-quantitative PCR, immunohistochemistry and western blot analysis demonstrated that hnRNP AB was upregulated in CRC tissues compared with the corresponding adjacent normal tissues. Immunohistochemical analyses indicated that a high expression of hnRNP AB was significantly associated with preoperative carcinoembryonic antigen (CEA; P<0.001) and carbohydrate antigen 19-9 (P=0.014) levels, tumour size (P=0.022) and infiltration (P=0.026), lymph node metastasis (P<0.001) and Tumour-Node-Metastasis stage (P<0.001). Univariate and multivariate Cox survival analyses revealed that hnRNP AB expression and preoperative CEA levels were significant independent factors affecting overall survival in patients with CRC (P<0.05). According to the Kaplan-Meier model, patients with CRC with high hnRNP AB expression exhibited significantly poorer prognosis compared with those with low hnRNP AB expression (P<0.001). In conclusion, the results of the present study demonstrated that hnRNP AB expression may serve an important role in the progression of CRC and that hnRNP AB may be considered a predictor of prognosis for patients with CRC.
Melatonin receptor heterodimerization in a photoreceptor-like cell line endogenously expressing melatonin receptors

Purpose Melatonin signaling plays an important role in the modulation of retinal physiology and photoreceptor viability during aging. In this study, we investigated whether 661W cells—a photoreceptor-like cell that endogenously expresses melatonin receptor type 1 (MT1) and melatonin receptor type 2 (MT2) receptors—represent a useful model for studying the biology of heterodimerization and signaling of MT1/2 receptors. Methods 661W cells were cultured, and MT1/MT2 heterodimerization in 661W cells was assessed with proximity ligation assay. MT2 was removed from the 661W cells using the MT2-CRISPR/Cas9 system. Melatonin receptor signaling was investigated by measuring cAMP levels and activation of the AKT-FoxO1 pathway. Results The results demonstrated that heterodimerization of MT1 and MT2 receptors occurs in 661W cells. The pathways activated by MT1/MT2 heterodimer (MT1/2h) in 661W cells are similar to those previously reported in mouse photoreceptors. Disruption of the heterodimer formation by genetically ablating MT2 from 661W cells abolished the activation of melatonin signaling in these cells. Conclusions The data indicated that in 661W cells, MT1 and MT2 receptors are functional only when they are associated in a heteromeric complex, as occurs in mouse photoreceptors. 661W cells represent a useful model for studying the mechanism underlying MT1/MT2 heterodimerization.
Effects of Baerveldt Glaucoma Implant Surgery on Corneal Endothelial Cells of Patients with No History of Trabeculectomy

Purpose Persistent corneal edema is a serious potential complication of Baerveldt glaucoma implant (BGI) surgery. A trabeculectomy reduces the density of corneal endothelial cells. We investigated the effect of BGI surgery on corneal endothelial cells of patients with no history of trabeculectomy. Methods We retrospectively analyzed 85 eyes of 85 patients who underwent BGI surgery and were followed-up for ≥12 months. We used new criteria for surgical failure. We defined persistent corneal edema or needed additional surgery for changing the tube position due to remarkable reduction in corneal endothelial cells as failure. We compared surgical outcomes with new criteria and the rates of corneal endothelial cell density (ECD) loss after BGI surgery between the anterior chamber insertion (AC) group (n=23) and vitreous cavity insertion (VC) group (n=63). Results The mean pre-operative ECD values of the AC and VC groups were not significantly different at 2309 ± 498 and 2204 ± 556 (p=0.426). The ECD reduction rate in the AC group was significantly faster than in the VC group. The mean post-operative IOP values significantly decreased in both groups. However, the VC group’s surgical outcomes were significantly better than the AC group’s (p=0.0241) with the new criteria. Conclusion The mean of ECD did not decrease significantly after BGI surgery in VC group patients with no history of trabeculectomy. BGI surgery insertion to the vitreous cavity was safe and had much less effect on the ECD decrease compared to insertion to the anterior chamber.
Cost-Effectiveness Of Once-Daily Single-Inhaler Triple Therapy In COPD: The IMPACT Trial

Background We assessed the cost-effectiveness of single-inhaler fluticasone furoate (FF)/umeclidinium (UMEC)/vilanterol (VI) versus FF/VI or UMEC/VI from a Canadian public healthcare perspective, incorporating data from the IMPACT trial in chronic obstructive pulmonary disease (COPD) (NCT02164513). Methods Baseline inputs and treatment effects from IMPACT were populated into the validated GALAXY-COPD disease progression model. Canadian unit costs and drug costs (Canadian dollars [C$], 2017) were applied to healthcare resource utilization and treatments. Future costs and health outcomes were discounted at 1.5% annually. Analyses were probabilistic, and outputs included exacerbation rates, costs, and life years (LYs) and quality-adjusted life years (QALYs) gained. Results Compared with FF/VI and UMEC/VI over a lifetime horizon, the analyses predicted that treatment with FF/UMEC/VI resulted in fewer moderate and severe exacerbations, more LYs and more QALYs gained, with a small incremental cost. The base-case incremental cost-effectiveness ratio (ICER) per QALY gained was C$18,989 (95% confidence interval [CI]: C$14,665, C$25,753) versus FF/VI and C$13,776 (95% CI: C$9787, C$19,448) versus UMEC/VI. FF/UMEC/VI remained cost-effective versus both FF/VI and UMEC/VI in all sensitivity analyses, including in scenario analyses that considered different intervention and comparator discontinuation rates, and treatment effects for subsequent therapy. Conclusion Treatment with FF/UMEC/VI was predicted to improve outcomes and be a cost-effective treatment option for patients with symptomatic COPD and a history of exacerbations compared with FF/VI or UMEC/VI, in Canada.