Miracle-dz/UniFAR-FTUs huggingface dataset:
Dendritic cell vaccination in melanoma patients: From promising results to future perspectives

ABSTRACT Dendritic cells (DCs) play an important role in the induction of antitumor immunity. Therefore, they are used as anti-cancer vaccines in clinical studies in various types of cancer. DC vaccines are generally well tolerated and able to induce antigen-specific T cell responses in melanoma patients. After DC vaccinations, functional tumor-specific T cells are more frequently detected in stage III melanoma patients, as compared to patients with advanced melanoma, indicating that the tumor load influences immunological responses. Furthermore, long-lasting clinical responses were rarely seen in metastatic melanoma patients after DC vaccination. Since more potent treatment options are available, e.g. immune checkpoint inhibitors and targeted therapy, DC vaccination as monotherapy may not be preferred in the treatment of advanced melanoma. However, encouraging results of DC vaccines combined with ipilimumab have been reported in advanced melanoma patients with an objective response rate of 38%. DC vaccines show promising clinical results in stage III patients, although clinical efficacy still needs to be proven in a phase 3 trial. The clinical and immunological results of DC vaccination in stage III melanoma patients might be further improved by using naturally circulating DCs (myeloid DCs and plasmacytoid DCs) and neoantigens to load DCs.
Observational study of spinal muscular atrophy type I and implications for clinical trials

Objectives: Prospective cohort study to characterize the clinical features and course of spinal muscular atrophy type I (SMA-I). Methods: Patients were enrolled at 3 study sites and followed for up to 36 months with serial clinical, motor function, laboratory, and electrophysiologic outcome assessments. Intervention was determined by published standard of care guidelines. Palliative care options were offered. Results: Thirty-four of 54 eligible subjects with SMA-I (63%) enrolled and 50% of these completed at least 12 months of follow-up. The median age at reaching the combined endpoint of death or requiring at least 16 hours/day of ventilation support was 13.5 months (interquartile range 8.1–22.0 months). Requirement for nutritional support preceded that for ventilation support. The distribution of age at reaching the combined endpoint was similar for subjects with SMA-I who had symptom onset before 3 months and after 3 months of age (p = 0.58). Having 2 SMN2 copies was associated with greater morbidity and mortality than having 3 copies. Baseline electrophysiologic measures indicated substantial motor neuron loss. By comparison, subjects with SMA-II who lost sitting ability (n = 10) had higher motor function, motor unit number estimate and compound motor action potential, longer survival, and later age when feeding or ventilation support was required. The mean rate of decline in The Children's Hospital of Philadelphia Infant Test for Neuromuscular Disorders motor function scale was 1.27 points/year (95% confidence interval 0.21–2.33, p = 0.02). Conclusions: Infants with SMA-I can be effectively enrolled and retained in a 12-month natural history study until a majority reach the combined endpoint. These outcome data can be used for clinical trial design.
The representation of the visual field in parvicellular and magnocellular layers of the lateral geniculate nucleus in the macaque monkey

Two‐dimensional maps of individual layers of the dorsal lateral geniculate nucleus (LGN) in the macaque monkey were constructed and used as a basis for comparing laminar size, shape, and topographic organization. Topographical data from the electrophysiological investigation of the LGN by Malpeli and Baker ('75) were displayed on maps of all six layers. As known from previous studies, there is a significant over‐representation of central vision in the LGN. Unexpectedly, though, the visual representation is anisotropic over portions of most LGN layers. That is, the linear magnification factor (millimeters along the laminar surface per degree of visual field) is not equal for all directions from a given point in the visual field. Moreover, the visual representations in the parvicellular and magnocellular divisions of the LGN differ both in their emphasis on central vision and in their anisotropies.
Geraniol attenuates 2-acetylaminofluorene induced oxidative stress, inflammation and apoptosis in the liver of wistar rats

Abstract 2-Acetylaminofluorene (2-AAF), is a well-known liver toxicant, generally used to induce tumors in laboratory animals. Geraniol (GE), a monoterpene found in essential oils of herbs and fruits, has been known to possess preventive efficacy against chemically induced toxicities. The present study was designed to analyze the protective effect of GE against 2-AAF induced oxidative stress, inflammation, hyperproliferation and apoptotic tissue damage in the liver of female Wistar rats. 2-AAF (0.02% w/w in diet) was administered and subjected to partial hepatectomy, as a mitogenic stimulus for the induction of hyperproliferation of liver tissue. GE was pre-treated orally at two different doses (100 and 200 mg/kg b.wt.) dissolved in corn oil. GE pre-treatment significantly ameliorated 2-AAF induced oxidative damage by diminishing tissue lipid peroxidation accompanied by the increase in enzymatic activities of catalase, glutathione peroxidase, glutathione reductase, superoxide dismutase and reduced glutathione content. The level of serum toxicity markers (AST, ALT, LDH) was found to be decreased. Pre-treatment with GE downregulated the expression of caspase-3,9, COX-2, NFkB, PCNA, iNOS, VEGF and significantly decreased disintegration of DNA. Histological findings further revealed that GE significantly restores the architecture of liver tissue. In the light of the above observations it may be concluded that GE may be used as preventive agent against 2-AAF induced oxidative stress, inflammation, hyperproliferation and apoptotic damage.
Plantaris excision in the treatment of non-insertional Achilles tendinopathy in elite athletes

Background Achilles tendinopathy is a serious and frequently occurring problem, especially in elite athletes. Recent research has suggested a role for the plantaris tendon in non-insertional Achilles tendinopathy. Aim To assess whether excising the plantaris tendon improved the symptoms of Achilles tendinopathy in elite athletes. Methods This prospective consecutive case series study investigated 32 elite athletes who underwent plantaris tendon excision using a mini-incision technique to treat medially located pain associated with non-insertional Achilles tendinopathy. Preoperative and postoperative visual analogue scores (VAS) for pain and the foot and ankle outcome score (FAOS) as well as time to return to sport and satisfaction scores were assessed. Results At a mean follow-up of 22.4 months (12–48), 29/32 (90%) of athletes were satisfied with the results. Thirty of the 32 athletes (94%) returned to sport at a mean of 10.3 weeks (5–27). The mean VAS score improved from 5.8 to 0.8 (p<0.01) and the mean FAOS improved in all domains (p<0.01). Few complications were seen, four athletes experienced short-term stiffness and one had a superficial wound infection. Conclusions The plantaris tendon may be responsible for symptoms in some athletes with non-insertional Achilles tendinopathy. Excision carries a low risk of complications and may provide significant improvement in symptoms enabling an early return to elite-level sports.
ABCB1 gene variants and antidepressant treatment outcome: A meta‐analysis

The efflux pump P‐glycoprotein (P‐gp), a gene product of the ABCB1 gene, plays a pivotal role in the transfer of various molecules across the blood–brain barrier. P‐gp protects the brain by selectively extruding its substrates, including certain antidepressive drugs, thereby limiting their uptake into the brain. Uhr et al. [2008] first showed that ABCB1 variants predicted the remission to antidepressants with P‐gp substrate properties in patients suffering from major depression (MD). Other studies investigating the influence of ABCB1 polymorphisms on antidepressant treatment response produced inconclusive results. In this meta‐analysis, we systematically summarized 16 pharmacogenetic studies focused on the association of ABCB1 variants and antidepressant treatment outcome in patients with MD (overall n = 2695). We investigated the association of treatment outcome and six ABCB1 single nucleotide polymorphisms (SNPs): rs2032583, rs2235015, rs2235040, rs1045642, rs2032582, rs1128503. We stratified for admission status, ethnicity, and prescription of concomitant medication. SNP rs2032583 showed a nominally significant association across all studies (P = 0.035, SNP was studied in a total of 2,037 patients) and a significant Bonferroni‐corrected association among inpatients (P = 1.5 × 10−05, n = 485). Also SNP rs2235015 was significantly associated with antidepressant treatment outcome withstanding Bonferroni correction (P = 3.0 × 10−04) among inpatients in a smaller subsample (n = 195). There were no significant associations of the other SNPs tested with antidepressant treatment outcome. Future pharmacogenetic association studies should focus on the role of the ABCB1 SNP rs2032583 in antidepressant outcome prediction. © 2015 Wiley Periodicals, Inc.
Zinc metabolism in fasted rats.

The effects of short-term starvation on serum and tissue levels of zinc, metallothionein (MT), and the activity of alkaline phosphatase (EC 3.1.3.1, ALP) were investigated with 6-month-old rats. The rats were fed a diet with adequate zinc (92mg/kg of Zn, 1.12% phytic acid) before they were starved for 0h (control), 12h, 24h, and 36h and then killed by decapitation. Fasting was accompanied by typical changes in serum parameters such as reduced glucose and protein concentrations, elevated ketogenesis, and a rapid breakdown of liver glycogen. Fasting did not alter serum zinc levels, but it did lead to a significant elevation in the percent of unsaturated serum-zinc binding capacity. Liver concentrations of zinc and MT, based both on fresh and dry weight, were increased throughout starvation. However, total liver zinc was reduced by up to 23% in response to fasting and total liver MT was slightly elevated. The increased concentrations of liver zinc and MT are, therefore, mainly a consequence of reduced liver weight. A part of the liver zinc, however, was bound to newly synthesized MT to prevent greater zinc loss. Starvation evoked no altered mucosa MT levels. Changes in kidney zinc and kidney medulla MT caused by starvation were small and not significant. In contrast to this observation some variation of kidney cortex MT was apparent. Starvation produced a permanent reduction of the serum and intestinal activity of ALP. In the liver and the medulla of the kidneys no significant differences of ALP activity could be observed. However, kidney cortex ALP was induced after 36h of fasting. (ABSTRACT TRUNCATED AT 250 WORDS)
The therapeutic results after laparoscopic hellers' myotomy and partial fundoplication for achalasia.

BACKGROUND/AIMS The aim of this prospectively designed study was to postoperatively assess the subjective complaints or relief of symptoms of achalasia patients' who underwent Laparoscopic Hellers' myotomy and partial fundoplication in our clinic. MATERIALS AND METHODS 40 patients were enrolled in the study that underwent Laparoscopic Hellers' myotomy and partial fundoplication (toupet or dor) for idiopathic achalasia in our clinic between years 2002 and 2012. Postoperative follow-up was conducted at 1st, 3rd. and 6th months in each patient for symptoms and a follow-up questionnaire was completed which is classified according to Vantrappen and Hellemans' modified classification. RESULTS 34 patients underwent Laparoscopic Heller myotomy with Toupet fundoplication whereas 6 patients underwent Laparoscopic Heller myotomy with Dor fundoplication. After 3 months, 2 patients' complaints of dysphagia were detected (5%). In the 6 month follow-up, one of these two patient dysphagia symptoms got worsened and a balloon dilatation was performed (2.5%). In the other one no clinical reason was found for dysphagia and medical therapy was initiated. In the 6 th month only three patients (7.5%) were presented with gastroesophageal reflux which successful medical treatment was initiated. CONCLUSION Laparoscopic myotomy with fundoplication seems to be the most effective surgical technique that provides both short and long term symptomatic relief with released hospitalization time and less complication rate.
Serum lipoprotein (a) levels and Behçet's disease: is there an association?

Background Behçet's disease (BD) is a multisystemic inflammatory disorder found in individuals with a particular genetic background. Hemostatic studies in BD support an imbalance towards a prothrombotic state at different levels. Lipoprotein (a) (Lp(a)) has atherogenic and thrombogenic properties. It is mostly under genetic regulation. We investigated the possible relationship between Lp(a) and BD.
Serum c‐erbB‐2 protein is a useful marker for monitoring tumor recurrence of the breast

C‐erbB‐2 oncogene protein (ErbB‐2/HER‐2) overexpression is a prognostic marker of breast carcinoma. The purpose of this study was to evaluate serum ErbB‐2 for monitoring tumor recurrence of operable breast carcinoma patients. The subjects were 86 breast carcinoma patients with stage I–IIIB. Sera were collected at preoperative and postoperative periods from 1996 to 2000. The cutoff value was set at 5.4 ng/ml for preoperative patients and at 6.5 ng/ml for postoperative patients. Twenty‐nine patients (34%) had higher preoperative serum ErbB‐2 levels (≥5.4 ng/ml). A higher preoperative serum ErbB‐2 was associated with higher clinical stage, larger tumor size, nodal metastasis, higher histologic grade and lymphatic invasion, but not with vascular invasion, hormonal receptor status or other tumor markers, such as carcinoembryonic antigen (CEA) and carbohydrate antigen 15‐3 (CA15‐3). As of April 2005, 27 patients (31%) had recurrence and 18 (62%) of them had a higher preoperative serum ErbB‐2. Seventeen patients died of tumor progression. The recurrence‐free survival rates at 7 years after breast surgery were 84% in 57 patients with a normal preoperative serum ErbB‐2 and 41% in 29 patients with a higher preoperative serum ErbB‐2 (p < 0.0001). The overall survival rates at 7 years were 93% and 55% (p < 0.0001), respectively. A multivariate analysis revealed that preoperative serum ErbB‐2 was an independent prognostic factor for recurrence‐free survival and overall survival in breast carcinoma patients. The specificities and sensitivities of postoperative tumor markers (CEA, CA15‐3 and ErbB‐2) were 91%, 100% and 85%, and 40%, 30% and 70%, respectively. Serum ErbB‐2 is a preoperative prognostic marker and may be useful for monitoring tumor recurrence of the breast. © 2006 Wiley‐Liss, Inc.
A controlled trial of naltrexone augmentation of nicotine replacement therapy for smoking cessation.

BACKGROUND Many smokers remain refractory to current therapies, which only partially address weight gain after smoking cessation. Thus, this study evaluated whether naltrexone hydrochloride augmentation of nicotine patch therapy improves smoking abstinence and reduces postcessation weight gain more than nicotine patch therapy alone and at what dose. METHODS Six-week double-blind placebo-controlled trial with follow-up in an outpatient research center. Four hundred individuals who smoked 20 or more cigarettes daily were randomly assigned to treatment for 6 weeks with a 21-mg nicotine patch and oral naltrexone hydrochloride (0, 25, 50, or 100 mg/d) after equal random treatment assignment and followed up for 1 year after randomization. The a priori specified primary end points were prolonged 4-week cigarette abstinence after a 2-week grace period in the intent-to-treat sample and weight gain in these abstainers. RESULTS We found no significant differences in prolonged 4-week abstinence (P = .49) or 6-week continuous abstinence after the quit date (P = .12) during treatment in the intent-to-treat analysis. Among 295 treatment completers, the 100-mg dose was associated with higher continuous abstinence rates (71.6%) compared with placebo (48%) (odds ratio, 2.73; 95% confidence interval, 1.39-5.39; P<.01). Among continuous abstainers, the 25-mg naltrexone hydrochloride group gained significantly less weight (mean +/- SEM, 0.7 +/- 0.31 kg) than the placebo group (mean +/- SEM, 1.9 +/- 0.33 kg; P<.01). Similar naltrexone dose effects on weight were found for those with prolonged abstinence and treatment completers, irrespective of abstinence. CONCLUSIONS The 100-mg dose of naltrexone hydrochloride appears the most promising for augmenting the efficacy of the nicotine patch on smoking cessation outcomes but requires further study. The significant weight reduction with low-dose naltrexone therapy suggests that it may be useful as a second-line treatment for weight-concerned smokers.
Reduction of MDSCs with All-trans Retinoic Acid Improves CAR Therapy Efficacy for Sarcomas

The efficacy of chimeric antigen receptor (CAR)–modified T cells against solid tumors is not proven. Retinoids are clinically accessible and were found to modulate tumor myeloid-derived suppressor cells, enhancing the efficacy of CAR therapies targeting solid tumors. Genetically engineered T cells expressing CD19-specific chimeric antigen receptors (CAR) have shown impressive activity against B-cell malignancies, and preliminary results suggest that T cells expressing a first-generation disialoganglioside (GD2)-specific CAR can also provide clinical benefit in patients with neuroblastoma. We sought to assess the potential of GD2-CAR therapies to treat pediatric sarcomas. We observed that 18 of 18 (100%) of osteosarcomas, 2 of 15 (13%) of rhabdomyosarcomas, and 7 of 35 (20%) of Ewing sarcomas expressed GD2. T cells engineered to express a third-generation GD2-CAR incorporating the 14g2a-scFv with the CD28, OX40, and CD3ζ signaling domains (14g2a.CD28.OX40.ζ) mediated efficient and comparable lysis of both GD2+ sarcoma and neuroblastoma cell lines in vitro. However, in xenograft models, GD2-CAR T cells had no antitumor effect against GD2+ sarcoma, despite effectively controlling GD2+ neuroblastoma. We observed that pediatric sarcoma xenografts, but not neuroblastoma xenografts, induced large populations of monocytic and granulocytic murine myeloid-derived suppressor cells (MDSC) that inhibited human CAR T-cell responses in vitro. Treatment of sarcoma-bearing mice with all-trans retinoic acid (ATRA) largely eradicated monocytic MDSCs and diminished the suppressive capacity of granulocytic MDSCs. Combined therapy using GD2-CAR T cells plus ATRA significantly improved antitumor efficacy against sarcoma xenografts. We conclude that retinoids provide a clinically accessible class of agents capable of diminishing the suppressive effects of MDSCs, and that co-administration of retinoids may enhance the efficacy of CAR therapies targeting solid tumors. Cancer Immunol Res; 4(10); 869–80. ©2016 AACR.
Associations between the standardized uptake value of (18)F-FDG PET/CT and demographic, clinical, pathological, radiological factors in lung cancer.

OBJECTIVES (18)F-fluoro-2-deoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) is extensively used to diagnose and stage of lung cancer. The aim of the current study was to investigate the correlation of demographic, clinical, pathological and radiological factors with primer tumor FDG Uptake in patients with lung cancer. MATERIALS AND METHODS This cross-sectional, clinical study was performed on a total of 57 lung cancer patients newly diagnosed that underwent FDG PET/CT. In addition to descriptive variables, histopathological diagnosis, tumor site and size, hemoglobin level, red cell distribution width, neutrophil to lymphocyte ratio were noted for each patient. The correlation of these variables to SUVmax values in FDG PET/CT was investigated. RESULTS A total of 57 patients (4 women, 53 men) with an average age of 60.8±9.4 (range: 33-89) participated in the study. Histopathological diagnoses were consistent with squamous cell carcinoma (28, 49.1%), adenocarcinoma (15, 26.3%) and small cell cancer (14, 24.6%). The SUVmax of primary tumor was positively correlated with tumor size (P<0.001). The tumor SUVmax of squamous cell carcinoma (SqCC) (17.49±8.37) was higher than that of adenocarcinoma (AC) (12.80±4.77) and small cell carcinoma (SCC) (12.40±5.80) (P=0.038). CONCLUSION SUVmax value was significantly higher for squamous cell carcinoma and it SUVmax values in PET scans was found to be positively correlated with tumor size. This study suggests that, tumor size and histologic subtype had influences upon FDG uptake in lung cancer.
Temporomandibular Disorders Treatment with Correction of Decreased Occlusal Vertical Dimension

BACKGROUND: The term decreased occlusal vertical dimension refers to the reduced distance between two anatomical points while the teeth are in a state of occlusion. The development of this situation is about some parafunctional activities of the masticatory system. AIM: To evaluate the value of decreased occlusal vertical dimension in cases with temporomandibular disorder and to follow up the influence of corrective treatment with occlusal splints and definitive prosthetic construction upon the elimination of clinical symptoms. MATERIAL AND METHODS: Eight cases with decreased occlusal vertical dimension accompanied with temporomandibular disorders were treated with an occlusal splint, as part of reversible occlusal treatment. After reducing, or complete elimination of the symptoms related to problems of decreased occlusal vertical dimension, the definitive prosthetic therapy was performed. RESULTS: The mean value of decreased occlusal vertical dimension in our patients is 8.5 mm, and the mean value of therapy time with an occlusal splint in these patients was 3.5 months. CONCLUSION: Occlusal splint is a part of reversible occlusal therapy in cases with decreased occlusal vertical dimension. After reducing the symptoms related to decreased occlusal vertical dimension definitive prosthetic therapy can be done.