Miracle-dz/UniFAR-FTUs huggingface dataset:
Treating the primary in metastatic prostate cancer: where do we stand?

PURPOSE OF REVIEW Traditionally, local treatment was reserved for palliative control of symptoms in men with metastatic prostate cancer. In the past few years there have been many advances in the systemic options available. The aim of this review is to explore the evidence in support of treating the primary tumor despite the presence of metastatic disease. RECENT FINDINGS There is a wealth of retrospective studies demonstrating advantages of local treatment [radical prostatectomy or radiation therapy (RT)] in metastatic disease. As these studies are prone to bias, treatment of the primary in the metastatic setting has not been adopted. However, two recent prospective randomized trials (HORRAD and STAMPEDE) have addressed the role of RT to the prostate in metastatic disease. The STAMPEDE sub-group analysis of low-volume metastatic disease demonstrated a survival advantage in favor of the RT arm (hazard ratio 0.68; 95% CI 0.52-0.90). The HORRAD trial showed a similar but nonsignificant trend towards RT (hazard ratio 0.68; 95% CI 0.42-1.10). As a result, the 2019 European Association of Urology and National Comprehensive Cancer Network guidelines now include RT to the prostate as an option in the setting of low-volume metastatic disease. SUMMARY Although systemic treatment remains standard of care for men with metastatic prostate cancer, there is recent compelling evidence from two prospective randomized trials supporting treatment of the prostate in oligometastatic disease.
Tetrahydrobiopterin, but Not l-Arginine, Decreases NO Synthase Uncoupling in Cells Expressing High Levels of Endothelial NO Synthase

Endothelial NO synthase (eNOS) produces superoxide when depleted of (6R)-5,6,7,8-tetrahydro-l-biopterin (BH4) and l-arginine by uncoupling the electron flow from NO production. High expression of eNOS has been reported to have beneficial effects in atherosclerotic arteries after relatively short periods of time. However, sustained high expression of eNOS may have disadvantageous vascular effects because of uncoupling. We investigated NO and reactive oxygen species (ROS) production in a microvascular endothelial cell line (bEnd.3) with sustained high eNOS expression and absent inducible NOS and neuronal NOS expression using 4,5-diaminofluorescein diacetate and diacetyldichlorofluorescein as probes, respectively. Unstimulated cells produced both NO and ROS. After stimulation with vascular endothelial growth factor (VEGF), NO and ROS production increased. VEGF-induced ROS production was even further increased by the addition of extra l-arginine. N&ohgr;-nitro-l-arginine methyl ester decreased ROS production. These findings strongly suggest that eNOS is a source of ROS in these cells. Although BH4 levels were increased as compared with another endothelial cell line, eNOS levels were >2 orders of magnitude higher. The addition of BH4 resulted in increased NO production and decreased generation of ROS, indicating that bEnd.3 cells produce ROS through eNOS uncoupling because of relative BH4 deficiency. Nevertheless, eNOS-dependent ROS production was not completely abolished by the addition of BH4, suggesting intrinsic superoxide production by eNOS. This study indicates that potentially beneficial sustained increases in eNOS expression and activity could lead to eNOS uncoupling and superoxide production as a consequence. Therefore, sustained increases of eNOS or VEGF activity should be accompanied by concomitant supplementation of BH4.
Exogenous Melatonin Enhances Cold, Salt and Drought Stress Tolerance by Improving Antioxidant Defense in Tea Plant (Camellia sinensis (L.) O. Kuntze)

Melatonin is a biological hormone that plays crucial roles in stress tolerance. In this study, we investigated the effect of exogenous melatonin on abiotic stress in the tea plant. Under cold, salt and drought stress, increasing malondialdehyde levels and decreasing maximum photochemical efficiency of PSII were observed in tea leaves. Meanwhile, the levels of reactive oxygen species (ROS) increased significantly under abiotic stress. Interestingly, pretreatment with melatonin on leaves alleviated ROS burst, decreased malondialdehyde levels and maintain high photosynthetic efficiency. Moreover, 100 μM melatonin-pretreated tea plants showed high levels of glutathione and ascorbic acid and increased the activities of superoxide dismutase, peroxidase, catalase and ascorbate peroxidase under abiotic stress. Notably, melatonin treatments can positively up-regulate the genes (CsSOD, CsPOD, CsCAT and CsAPX) expression of antioxidant enzyme biosynthesis. Taken together, our results confirmed that melatonin protects tea plants against abiotic stress-induced damages through detoxifying ROS and regulating antioxidant systems.
Palliative Electrochemotherapy in Vulvar Carcinoma: Preliminary Results of the ELECHTRA (Electrochemotherapy Vulvar Cancer) Multicenter Study

Vulvar cancer (VC) is a rare disease of which recurrence poses management problems due to patients’ advanced age and comorbidities, and to the localization of the disease. Palliative treatments, allowing local disease control in patients previously treated with multimodal therapies or with comorbidities, are lacking. In this study we tested electrochemotherapy (ECT) on recurrent VC refractory to standard therapies to assess the tumor response and to define the selection criteria for patient’s candidate to ECT. This is a multicenter observational study carried out in five Italian centers. Data about patients and tumor characteristics, treatment, toxicity, and clinical response were recorded. In all procedures, intravenous bleomycin was administered according to European Standard Operative Procedure ECT (ESOPE) guidelines. Sixty-one patients, with a median age 79 years (range: 39–85) and mainly affected by squamous cellular carcinoma (91.8%), were treated with ECT. No serious adverse events were reported. Patients were discharged after three days (median, range: 0–8 days). Two months after ECT, the clinical response rate was 83.6% and was not related to age, body mass index, International Federation of Gynecology and Obstetrics (FIGO) stage, number of treated nodules, or previous treatments. ECT is a safe procedure with a favorable cost-effectiveness ratio and should be considered as a treatment option for local disease control in patients unsuitable for standard therapies.
Proximal Junctional Kyphosis in Adolescent Idiopathic Scoliosis Following Segmental Posterior Spinal Instrumentation and Fusion: Minimum 5-Year Follow-up

Study Design. A retrospective study. Objective. To analyze the long-term proximal junctional change in adolescent idiopathic scoliosis (AIS) following segmental posterior spinal instrumentation and fusion 5 years or more after surgery. Summary of Background Data. No study has concentrated on time-dependent long-term proximal junctional change in AIS following segmental posterior spinal instrumentation and fusion after 5 years postoperation. Risk factors for developing proximal junctional kyphosis (PJK) are unknown. Methods. A total of 193 consecutive AIS patients with a minimum 5-year follow-up (average, 7.3 years; range, 5–16.7 years) treated with segmental posterior spinal instrumentation and fusion were evaluated. Radiographic measurements analyzed included sagittal Cobb angle at the proximal junction on preoperative, early postoperation, 2-year postoperation, and final follow-up (≥5 years) by standing long cassette radiographs. Postoperative Scoliosis Research Society (SRS)-24 outcome scores were also evaluated. Abnormal PJK was defined as the final proximal junctional sagittal Cobb angle between the lower endplate of the uppermost instrumented vertebra and the upper endplate of two vertebrae supra-adjacent, which was > 10° and at least 10° greater than the preoperative measurement. Results. The incidence of PJK at 7.3 years postoperation was 26% (50 of 193 patients). The average proximal junctional angle increased 15.2° until 2 years postoperation and then increased 1.7° until final follow-up in the PJK group (n = 50). Factors that were statistically significant for PJK development were as follows: a thoracoplasty procedure (P = 0.001), preoperative hyperkyphotic thoracic alignment (T5–T12 > 40°) (P = 0.015), and hybrid instrumentation (proximal hooks and distal pedicle screws) compared with the hooks only group (P = 0.029). The number of fused vertebrae more than 11 was also related with PJK (P = 0.08). The level of the uppermost instrumented vertebra did not affect the PJK incidence. SRS-24 outcome scores did not demonstrate any significant differences (P = 0.54 for total score and P = 0.49 for self-image subscale) between the PJK and non-PJK groups. Conclusion. The incidence of proximal junctional kyphosis at 7.3 years postoperation was 26% and did not progress significantly after 2 years postoperation. Risk factors for developing PJK were an associated thoracoplasty, hybrid instrumentation (proximal hooks and distal pedicle screws), and a preoperative larger sagittal thoracic Cobb angle (T5–T12 > 40°). The SRS-24 outcome instrument was not affected by PJK.
Smoking habits, knowledge about and attitudes toward smoking among employees in health institutions in Serbia.

BACKGROUND/AIM According to the number of active smokers, Serbia occupies a high position in Europe, as well as worldwide. More than 47% of adults are smokers according to WHO data, and 33.6% according to the National Health Survey Serbia in 2006. Smoking physicians are setting a bad example to patients, they are uncritical to this habit, rarely ask patients whether they smoke and rarely advise them not to smoke. These facts contribute to the battle for reducing the number of medical workers who smoke, as well as the number of smokers among general population. The aim of the study was to determine the smoking behavior, knowledge and attitudes and cessation advice given to patients by healthcare professionals in Serbia. METHODS A stratified random cluster sample of 1,383 participants included all types of health institutions in Serbia excluding Kosovo. The self administrated questionnaire was used to collect data about smoking habits, knowledge, attitudes and cessation advice to patients given by health professionals in Serbia. RESULTS Out of 1,383 participants, 45.60% were smokers, of whom 34.13% were physicians and 51.87% nurses. There were 46.4% male and 45.4% female smokers. The differences in agreement with the statements related to the responsibilities of health care professionals and smoking policy are significant between the "ever" and "never" smokers, and also between physicians and nurses. Twenty-five percent of nurses and 22% of doctors claimed they had received formal training. However, only 35.7% of the healthcare professionals felt very prepared to counsel patients, while 52.7% felt somewhat prepared and 11.6% were not prepared at all. CONCLUSIONS According to the result of this survey, there are needs for more aggressive nationwide non-smoking campaigns for physicians and medical students. Experiences from countries where physicians smoke less and more effectively carry out smoking cessation practices need to be shared with Serbian physicians in order to improve their smoking behavior and smoking cessation practices.
Soil Application of Effective Microorganisms (EM) Maintains Leaf Photosynthetic Efficiency, Increases Seed Yield and Quality Traits of Bean (Phaseolus vulgaris L.) Plants Grown on Different Substrates

EM (effective microorganisms) is a biofertilizer consisting of a mixed culture of potentially beneficial microorganisms. In this study, we investigated the effects of EM treatment on leaf in vivo chlorophyll a fluorescence of photosystem II (PSII), yield, and macronutrient content of bean plants grown on different substrates (nutrient rich substrate vs. nutrient poor sandy soil) in controlled environmental conditions (pot experiment in greenhouse). EM-treated plants maintained optimum leaf photosynthetic efficiency two weeks longer than the control plants, and increased yield independent of substrate. The levels of seed nutritionally-relevant molecules (proteins, lipids, and starch) were only slightly modified, apart from the protein content, which increased in plants grown in sandy soil. Although EM can be considered a promising and environmentally friendly technology for sustainable agriculture, more studies are needed to elucidate the mechanism(s) of action of EM, as well as its efficacy under open field conditions.
Associations of TLR4 gene polymorphisms with the risk of age-related macular degeneration in a Chinese Han population

Abstract The study was designed to reveal the relationship of toll-like receptor 4 (TLR4, rs1927914 and rs1927907) polymorphisms with risk of age-related macular degeneration (AMD), as well as the adjustment of this association by some environmental and lifestyle factors in Chinese Han population. TLR4 polymorphisms were genotyped by polymerase chain reaction-restricted fragment length polymorphisms and direct sequencing method in 138 AMD patients and 146 healthy controls. Genotype distribution in the control group was checked with Hardy–Weinberg equilibrium. Association of TLR4 polymorphisms and AMD risk was evaluated by &khgr;2 test and adjusted by age and sex, smoking and drinking. Odds ratio (OR) with 95% confidence interval (95% CI) was used to represent the association strength. Logistic regressive analysis was used to calculate the adjusted OR values. CC genotype of rs1927914 had significantly lower frequency in AMD patients (P = .010), indicated a negative association with AMD risk (crude: OR = 0.358, 95% CI = 0.162–0.791; adjusted: OR = 0.355, 95% CI = 0.160–0.789). C allele of rs1927914 might decrease the susceptibility of AMD (crude: OR = 0.698, 95% CI = 0.497–0.982; adjusted: OR = 0.698, 95% CI = 0.495–0.984). No significant association has been discovered between TLR4 rs1927907 polymorphism and AMD susceptibility. Strong linkage disequilibrium existed between rs1927914 and rs1927907 polymorphisms. C-C haplotype was negatively associated with AMD risk (OR = 0.242, 95% CI = 0.121–0.485; OR = 0.242, 95% CI = 0.120–0.488). CC genotype and C allele of rs1927914 were significantly associated with the decreased AMD susceptibility.
A clinical research on the potential pathogenesis of somatic cancer related cerebral venous sinus thrombosis

Abstract To investigate the pathogenesis of somatic solid cancer-related cerebral venous sinus thrombosis (CVST). A total of 174 patients with CVST were recruited from the hospital between January 2006 and December 2017 and divided into two groups: (1) somatic cancer-related CVST group, defined as active somatic solid cancer patients with acute CVST; (2) cancer group (CG), defined as active somatic solid cancer patients without CVST. The cancer group patients were age and gender-matched somatic cancer-related CVST group patients. In addition, the types and amount distribution of cancer in cancer group were also matched with somatic cancer-related CVST group patients. Compared to cancer group patients, somatic cancer-related CVST group patients had more intracranial metastasis, a higher platelet count, higher plasma D-dimer, carcinoembryonic antigen (CEA) and cancer antigen (CA) 125 levels, a greater platelet to lymphocyte ratio (PLR), and a greater platelet to neutrophil ratio (PNR). The risk for CVST in somatic cancer-related CVST group patients increased independently by 0.7% (odds ratio [OR] 1.007; 95% confidence interval [CI] 1.000, 1.015; P = .047) with a 1 ng/ml increase in D-dimer levels, by 4.6% (OR 1.046; 95% CI 1.011, 1.083; P = .010) with a 1 U/ml increase in CEA, by 2.7% (OR 1.027; 95% CI 1.003, 1.051; P = .025) with a 1 U/ml increase in CA125, and by 10.6% (OR 1.106; 95% CI 1.002, 1.220; P = .045) with a 1 unit increase in PNR. It was suggested that together impacts of elevated plasma D-dimer, CA125, CEA levels, and a greater PNR may lead to hypercoagulability and to trigger the development of cancer-related CVST.
Antikeratin antibody in rheumatoid and psoriatic arthritis.

SIR, We note with interest the report on spontaneous rupture of weight bearing tendons in systemic lupus erythematosus (SLE). ' We report a case of rupture of a non-weight bearing tendon, namely the long head of biceps. A 35 year old woman had a six year history of SLE, which has been clinically quiescent since 1982. In January 1985 she sustained a fracture of the surgical neck of the left humerus with minimal displacement. This was treated conservatively, and she made an uneventful recovery. In August 1985 she presented with a one month history of spontaneous swelling in the left arm. Examination showed
Can Evaluative Conditioning Change Well-Established Attitudes Towards Popular Brands? Your Brain Says Yes Even Though Your Mouth Says No

In the present study, using both implicit and explicit measures, we addressed the issue of whether strongly developed relationships towards brands could be modified through the use of evaluative conditioning. Using an online survey, individual participant brand lists were created, and formed the basis of this experiment. Participants were then exposed to conditioning during a longitudinal study. Throughout the experiment, a combination of explicit and implicit measures was used to assess changes in attitude. Specifically, participants were asked to rate the brand names on a Likert-type scale. Simultaneously, changes in the brains electrical activity in response to the brands were recorded via electroencephalography (EEG). Upon completion of this task, participants underwent two Implicit Association Tests (IAT; one for liked brands and one for disliked brands). There were two main findings of this study. Firstly, no significant changes in attitude were observed via the use of explicit measures, and those that were found relating to the IAT were regarded as questionable. Secondly, EEG presented consistent results which showed that conditioning elicited changes in cortical activity towards both liked and disliked brands, which suggest it may be a useful tool in measuring the impact of evaluative conditioning that is not reflected in verbal responses.
Transcriptome Analysis of the Breast Muscle of Xichuan Black-Bone Chickens Under Tyrosine Supplementation Revealed the Mechanism of Tyrosine-Induced Melanin Deposition

The Xichuan black-bone chicken, which is a rare local chicken species in China, is an important genetic resource of black-bone chickens. Tyrosine can affect melanin production, but the molecular mechanism underlying tyrosine-induced melanin deposition in Xichuan black-bone chickens is poorly understood. Here, the blackness degree and melanin content of the breast muscle of Xichuan black-bone chickens fed a basic diet with five levels of added tyrosine (i.e., 0.2, 0.4, 0.6, 0.8, and 1.0%; these groups were denoted test groups I-V, respectively) were assessed, and the results showed that 0.8% tyrosine was the optimal level of added tyrosine. Moreover, the effects of tyrosine supplementation on the proliferation and tyrosinase content of melanocytes in Xichuan black-bone chickens were evaluated. The results revealed a dose-dependent relationship between tyrosine supplementation and melanocyte proliferation. In addition, 417 differentially expressed genes (DEGs), including 160 upregulated genes and 257 downregulated genes, were identified in a comparative analysis of the transcriptome profiles constructed using the pooled total RNA from breast muscle tissues of the control group and test group IV, respectively (fold change ≥2.0, P < 0.05). These DEGs were mainly involved in melanogenesis, the calcium signaling pathway, the Wnt signaling pathway, the mTOR signaling pathway, and vascular smooth muscle contraction. The pathway analysis of the DEGs identified some key genes associated with pigmentation, such as DCT and EDNRB2. In summary, the melanin content of breast muscle could be markedly enhanced by adding an appropriate amount of tyrosine to the diet of Xichuan black-bone chickens, and the EDNRB2-mediated molecular regulatory network could play a key role in the biological process of tyrosine-induced melanin deposition. These results have deepened the understanding of the molecular regulatory mechanism of melanin deposition in black-bone chickens and provide a basis for the regulation of nutrition and genetic breeding associated with melanin deposition in Xichuan black-bone chickens.
Is There a Role of Autophagy in Depression and Antidepressant Action?

Autophagy has been recognized as evolutionary conserved intracellular pathway that ensures energy, organelle, and protein homeostasis through lysosomal degradation of damaged macromolecules and organelles. It is activated under various stress situations, e.g., food deprivation or proteotoxic conditions. Autophagy has been linked to several diseases, more recently also including stress-related diseases such as depression. A growing number of publications report on the role of autophagy in neurons, also referred to as “neuronal autophagy” on the one hand, and several studies describe effects of antidepressants—or of compounds that exert antidepressant-like actions—on autophagy on the other hand. This minireview highlights the emerging evidence for the involvement of autophagy in the pathology and treatment of depression and discusses current limitations as well as potential avenues for future research.
Association Between HTLV-1 Genotypes and Risk of HAM/TSP

Human T-cell leukemia virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a neurological disorder presenting with spastic paraparesis, sphincter dysfunction, and mild sensory disturbance in the lower extremities, which develops in a small minority of HTLV-1-infected individuals. HTLV-1-specific T cells are efficiently activated through dedicated human leukocyte antigen-mediated mechanisms, a process considered deeply involved with its pathogenesis. It has been reported that the lifetime risk of developing HAM/TSP differs between ethnic groups, and there is an association between HTLV-1 tax gene subgroups (i.e., tax subgroup-A or -B), which correspond to HTLV-1 “cosmopolitan subtype 1a subgroup A (i.e., transcontinental subgroup)” and “cosmopolitan subtype 1a subgroup B (i.e., Japanese subgroup),” respectively, and the risk of HAM/TSP in the Japanese population. These findings suggest that a given host’s susceptibility to HAM/TSP is deeply connected with both differences in genetically determined components of the host immune response and HTLV-1 subgroup. Therefore, it is crucial for ongoing work to focus on developing novel treatments and preventative approaches for HAM/TSP. In this review, based on an overview of the topic and our latest research findings, the role of the HTLV-1 subgroup on the effects of virus–host interactions in the pathogenesis of HAM/TSP is discussed.