Miracle-dz/UniFAR-FTUs huggingface dataset:
Metabolomics and eicosanoid analysis identified serum biomarkers for distinguishing hepatocellular carcinoma from hepatitis B virus-related cirrhosis

Hepatocellular carcinoma (HCC) is one of the most common cancers in the world. It is a type of inflammation-related cancer that usually follows liver hepatitis that mostly caused by hepatitis B virus (HBV) in China. However, the metabolism disturbance of HCC and HBV-cirrhosis is not yet fully understood. In addition, there is little research on the relationships between inflammation mediators and HCC. In this study, we investigated serum metabolic abnormalities in HBV-cirrhosis and HCC patients through non-targeted metabolomics and targeted eicosanoid analysis. Metabolomic analysis identified 14 metabolites, i.e. malate, citrate, succinate, lysine, carnitine, proline, ornithine, serine, phenylalanine, tyrosine, arachidonic acid arabinose, galactose and uric acid are consistently altered in HBV-cirrhosis and HCC patients. Meanwhile, eicosanoid analysis uncovered several prostaglandins and leukotrienes are implicated in pathological processes in HBV-cirrhosis and HCC. Finally, these identified biomarkers possessed strong potential to distinguish and diagnose HCC from healthy controls and HBV-cirrhosis patients. This study provided a new perspective to understand the mechanism and discover probable biomarkers of HCC.
A small cysteine-rich protein from two kingdoms of microbes is recognized as a novel pathogen-associated molecular pattern.

Pathogen-associated molecular patterns (PAMPs) are conserved molecules that are crucial for normal life cycle of microorganisms. However, the diversity of microbial PAMPs is little known. During screening of cell-death-inducing factors from the necrotrophic fungus Valsa mali, we identified a novel PAMP VmE02 that is widely spread in oomycetes and fungi. Agrobacterium tumefaciens-mediated transient expression or infiltration of recombinant protein produced by Escherichia coli was performed to assay elicitor activity of the proteins tested. Virus-induced gene silencing in Nicotiana benthamiana was used to determine the components involved in VmE02-triggered cell death. The role of VmE02 in virulence and conidiation of V. mali were characterized by gene deletion and complementation. We found that VmE02, together with some of its homologues from both oomycete and fungal species, exhibited cell-death-inducing activity in N. benthamiana. VmE02-triggered cell death was shown to be dependent on BRI1-ASSOCIATED KINASE-1, SUPPRESSOR OF BIR1-1, HSP90 and SGT1 in N. benthamiana. Deletion of VmE02 in V. mali greatly attenuated pathogen conidiation but not virulence, and treatment of N. benthamiana with VmE02 enhances plant resistance to Sclerotinia sclerotiorum and Phytophthora capsici. We conclude that VmE02 is a novel cross-kingdom PAMP produced by several fungi and oomycetes.
Preventive effect of omega‐3 fatty acids in a rat model of stress‐induced liver injury

Omega‐3 fatty acids are gaining attention as a therapeutic agent of many diseases. Their protective effect in a variety of diseases has been demonstrated. To the best of our knowledge, this is the first study on omega‐3 fatty acids related to acute cold‐restraint stress (CRS) induced hepatic dysfunction in rats. Forty adult male Sprague–Dawley albino rats were used and classified into: control, omega‐3 group, each rat was pretreated with omega‐3 fatty acids; CRS group, rats were subjected to acute CRS for 6 hr; and CRS group pretreated with omega‐3 fatty acids. Serum was obtained to determine corticosterone (CORT), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and tumor necrosis factor‐α (TNF‐α) levels. Hepatic malondialdehyde (MDA) and total antioxidant capacity (TAC) levels were measured. Also, liver tissues were taken for histological examination and immunohistochemical assessment of the apoptotic marker, caspase‐3. Results showed that pretreatment of stressed rats with omega‐3 fatty acids led to significant decrease in hepatic MDA and increase in TAC levels. They reduced serum levels of CORT, ALT, AST, and TNF‐α. Also, they improved liver damage and suppressed hepatic caspase‐3 expression. In conclusion, pretreatment of stressed rats with omega‐3 fatty acids has ameliorated stress‐induced liver damage due to their antioxidant, anti‐inflammatory, and antiapoptotic effects. So, they can be used to minimize stress complications on the liver.
Relationship between treatment and period of absence among employees on sick leave due to mental disease

This study used health insurance claims data to examine the relationship between the length of sick leave and treatment administered to employees who received middle- to long-term accident and sickness benefits for ≥91 d due to mood disorders, anxiety, and dissociative, stress-related, somatoform and other nonpsychotic mental disorders. Employees who received psychotherapy had significantly shorter leaves of absence over one year compared to those that did not. Treatment with psychotropic drugs was significantly higher among those on leave for ≤365 d than those on leave for ≥366 d. Age, sex and hospital treatment were not significantly associated with length of sick leave. These results suggest that professional psychological treatment is associated with length of sick leave.
In vivo Assessment of Combined Effects of Glibenclamide and Losartan in Diabetic Rats

Objective: Diabetic complications involve multiple pathological pathways, including hyperglycemia-induced oxidative stress and inflammation. Combination therapy is usually employed to improve treatment outcomes and to lower potential adverse effects. In this study, we evaluated the effects of antidiabetic and antihypertensive agents, glibenclamide (GLI) and losartan (LT), on diabetes mellitus (DM)-associated metabolic changes in rats. Materials and Methods: Streptozotocin-induced diabetic animals were orally treated with GLI 5 mg/kg and/or LT 25 mg/kg for 4 weeks. Blood glucose, insulin, aspartate aminotransferase, alanine aminotransferase, urinary creatinine, and urea levels were measured. Serum, liver, and kidney values of inflammatory markers, such as interleukin-1β, tumor necrosis factor alpha, and interleukin-6 were assessed, along with lipid peroxidation products (e.g., thiobarbituric acid reactive substances), endogenous antioxidants (e.g., glutathione), as well as antioxidant enzyme activities (e.g., catalase, superoxide dismutase, and glutathione peroxidase). Finally, histological changes in liver and kidney tissues were evaluated. Results: DM markedly induced systemic, hepatic, and renal inflammation and lowered antioxidant defense mechanisms. Treatment of diabetic rats with either GLI or LT significantly improved liver and kidney functions and histological structure. Moreover, both medications reduced signs of oxidative stress and inflammation in blood, liver, and kidney samples. Combining GLI and LT showed similar protective potential against systemic, hepatic, and renal oxidative stress and inflammation. Conclusion: Adding LT to GLI therapy revealed prospective antioxidant and anti-inflammatory action, while no synergistic or additive effects were observed.
Oxygen-ozone therapy as support and palliative therapy in 50 cancer patients with fatigue - A short report.

OBJECTIVE Fatigue may be cause by all cancer treatments, maybe because the tissue damage or the build-up of dead cells derived products. PATIENTS AND METHODS At the Mede Clinic in Sacile, Pordenone, Italy, from February 2016 to May 2018 we studied 50 patients with cancer and fatigue (15 with breast cancer, 12 with lung cancer, 11 with colon cancer, 5 with renal cancer, 3 with prostate cancer, 2 with melanoma and 2 hepatocellular carcinoma). Patients were treated with Auto Hemotransfusion (GAE) according to the SIOOT (Scientific Society of Oxygen Ozone Therapy) protocols, two times a week for one month and then twice monthly as maintenance therapy. RESULTS Nineteen of them were undergoing neoplastic treatment, 10 had already ended the cancer therapy and 21 were in a palliative setting. The Fatigue Severity Scale was used to assess the extent of fatigue in patients, in order to estimate the severity of the symptom with a score from 1 to 7. No side effects were found, and 35 patients (70%) achieved a significant improvement (> 50%) of the symptoms. CONCLUSIONS Our preliminary data demonstrate that ozone therapy is a valid supportive therapy for fatigue in cancer patients, both during cancer therapy and in a palliative setting with no significant side effects.
Evaluating the Effects of Metalinguistic and Working Memory Training on Reading Fluency in Chinese and English: A Randomized Controlled Trial

Children traditionally learn to read Chinese characters by rote, and thus stretching children’s memory span could possibly improve their reading in Chinese. Nevertheless, 85% of Chinese characters are semantic-phonetic compounds that contain probabilistic information about meaning and pronunciation. Hence, enhancing children’s metalinguistic skills might also facilitate reading in Chinese. In the present study, we tested whether training children’s metalinguistic skills or training their working-memory capacity in 8 weeks would produce reading gains, and whether these gains would be similar in Chinese and English. We recruited 35 second graders in Hong Kong and randomly assigned them to a metalinguistic training group (N = 13), a working-memory training group (10), or a waitlist control group (12). In the metalinguistic training, children were taught to analyze novel Chinese characters into phonetic and semantic radicals and novel English words into onsets and rimes. In the working-memory training, children were trained to recall increasingly long strings of Cantonese or English syllables in correct or reverse order. All children were tested on phonological skills, verbal working memory, and word reading fluency in Chinese and in English before and after training. Analyses of the pre- and post-test data revealed that only the metalinguistic training group, but not the other two groups, showed significant improvement on phonological skills in Chinese and English. Working-memory span in Chinese and English increased from the pre- to post-test in the working-memory training group relative to other two groups. Despite these domain-specific training effects, the two training groups improved similarly in word reading fluency in Chinese and English compared to the control group. Our findings suggest that increased metalinguistic skills and a larger working-memory span appear equally beneficial to reading fluency, and that these effects are similar in Chinese and English.
Liver surgery prolongs the survival of patients with gastrointestinal stromal tumor liver metastasis: a retrospective study from a single center

Objectives Gastrointestinal stromal tumor (GIST) liver metastasis (GLM) is a special subset of advanced GIST, because its lesions are easier to define and assess. We aim to determine the role of liver metastasectomy for patients with GLM in the era of tyrosine kinase inhibitor (TKI) therapy. Methods We reviewed patients with metastatic GIST who received surgery or other treatments in Sun Yat-sen University Cancer Center between January 1991 and December 2017. Patients with metastases confined to the liver and with no previous metastasis to other locations were included into the study and were classified into surgical and non-surgical groups. All patients received 400 mg/d imatinib after the operation. We compared progression-free survival (PFS) and overall survival (OS) between the two groups. Results A total of 102 patients were included into the study. Of them, 21 (20.1%) underwent surgery for liver metastases and 81 (79.9%) received TKI therapy alone. During the operation, six patients received radiofrequency ablation for suspicious or unresectable lesions. Three-year PFS rate was 77.5% in the surgical group and 65.5% in the non-surgical group (P=0.027); 5-year OS rate was 85.7% and 59.6%, respectively (P=0.008). About 22.1% of patients had metastases of less than three in the surgical group, while the rate was 42.9% in the non-surgical group (P=0.011). Patients with metastases of less than three had longer PFS than those with three or more, with a 3-year PFS rate of 72.8% and 65.8%, respectively (P=0.019). But their difference in 5-year OS rate was not significant (91.7% vs 55.3%, P=0.08). Conclusion Followed by continuous TKI therapy, R0 surgery significantly prolongs the survival of patients with GLM, regardless of the extent of disease or the phase of metastasis.
The yeast copper chaperone for copper-zinc superoxide dismutase (CCS1) is a multifunctional chaperone promoting all levels of SOD1 maturation

Copper (Cu) is essential for the survival of aerobic organisms through its interaction with molecular oxygen (O2). However, Cu's chemical properties also make it toxic, requiring specific cellular mechanisms for Cu uptake and handling, mediated by Cu chaperones. CCS1, the budding yeast (S. cerevisiae) Cu chaperone for Cu–zinc (Zn) superoxide dismutase (SOD1) activates by directly promoting both Cu delivery and disulfide formation in SOD1. The complete mechanistic details of this transaction along with recently proposed molecular chaperone-like functions for CCS1 remain undefined. Here, we present combined structural, spectroscopic, kinetic, and thermodynamic data that suggest a multifunctional chaperoning role(s) for CCS1 during SOD1 activation. We observed that CCS1 preferentially binds a completely immature form of SOD1 and that the SOD1·CCS1 interaction promotes high-affinity Zn(II) binding in SOD1. Conserved aromatic residues within the CCS1 C-terminal domain are integral in these processes. Previously, we have shown that CCS1 delivers Cu(I) to an entry site at the SOD1·CCS1 interface upon binding. We show here that Cu(I) is transferred from CCS1 to the entry site and then to the SOD1 active site by a thermodynamically driven affinity gradient. We also noted that efficient transfer from the entry site to the active site is entirely dependent upon the oxidation of the conserved intrasubunit disulfide bond in SOD1. Our results herein provide a solid foundation for proposing a complete molecular mechanism for CCS1 activity and reclassification as a first-of-its-kind “dual chaperone. ”
The value of immunotherapy in head and neck cancer

ABSTRACT Introduction: Head and neck squamous cell carcinomas (HNSCC) previously had limited treatment options once patients had progressed on systemic chemotherapy. With recent advances, immunotherapy now plays an important role in the treatment of advanced disease with improved outcomes as compared to cytotoxic chemotherapy. Areas covered: This article reviews the effects of the immune system and how it influences the development and response to HNSCC therapy. We additionally provide a summary of immunotherapy treatments available as well as their applicable clinical trials that led to their approval. Expert Commentary: The challenges that need to be addressed in order to maximize the benefits of immunotherapy in HNSCC are the selection criteria for immune checkpoint inhibitors and the optimization of combination regimens of immunotherapeutics or chemo-immunotherapy. Furthermore, there remains to be a lack of knowledge in how to incorporate molecular biomarkers as predictors of response to HNSCC immunotherapy.
Outcome of Patients with Complete Unilateral Cleft Lip and Palate: 20-Year Follow-Up of a Treatment Protocol

Background: The treatment plan for cleft lip and palate varies among centers and requires long-term evaluation of its final outcome. Methods: A consecutive series of patients born from 1994 to 1996 were reviewed. Inclusion criteria were complete unilateral cleft lip and palate, undergoing all treatment procedures performed by the team, and continuous follow-ups until 20 years of age. Exclusion criteria were incomplete data, having microform cleft lip on the contralateral side, presence of the Simonart band, and other abnormalities. Results: A total of 72 patients were included. Average age at final evaluation was 21.3 years; 83.3 percent of patients underwent one-stage rotation-advancement lip repair and 16.7 percent underwent two-stage repair with an initial adhesion cheiloplasty. All patients underwent palate repair using the two-flap method at an average age of 12.3 months. Velopharyngeal insufficiency occurred and required surgical interventions in 19.4 percent during the preschool age and in 16.7 percent at the time of alveolar bone grafting; 56.9 percent of patients underwent secondary lip/nose revision during the growing age. Regular orthodontic treatment was administered to 34.7 percent of patients between 12 and 16 years of age. Orthodontic treatment and orthognathic surgery were applied in 37.5 percent of the patients after maturity. The average number of surgical procedures to complete the treatment was 4.8 per patient. Conclusions: This treatment protocol provided generally acceptable final outcome after the 20-year follow-up. Some results were less ideal and have resulted in modifications of the planning and methods in the protocol. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.
A new simple method for quantification and locating P and N reserves in microalgal cells based on energy-filtered transmission electron microscopy (EFTEM) elemental maps

We established a new simple approach to study phosphorus (P) and nitrogen (N) reserves at subcellular level potentially applicable to various types of cells capable of accumulating P- and/or N-rich inclusions. Here, we report on using this approach for locating and assessing the abundance of the P and N reserves in microalgal and cyanobacterial cells. The approach includes separation of the signal from P- or N-rich structures from noise on the energy-filtered transmission electron microscopy (EFTEM) P- or N-maps. The separation includes (i) relative entropy estimation for each pixel of the map, (ii) binary thresholding of the map, and (iii) segmenting the image to assess the inclusion relative area and localization in the cell section. The separation is based on comparing the a posteriori probability that a pixel of the map contains information about the sample vs. Gaussian a priori probability that the pixel contains noise. The difference is expressed as relative entropy value for the pixel; positive values are characteristic of the pixels containing the payload information about the sample. This is the first known method for quantification and locating at a subcellular level P-rich and N-rich inclusions including tiny (< 180 nm) structures. We demonstrated the applicability of the proposed method both to the cells of eukaryotic green microalgae and cyanobacteria. Using the new method, we elucidated the heterogeneity of the studied cells in accumulation of P and N reserves across different species. The proposed approach will be handy for any cytological and microbiological study requiring a comparative assessment of subcellular distribution of cyanophycin, polyphosphates or other type of P- or N-rich inclusions. An added value is the potential of this approach for automation of the data processing and evaluation enabling an unprecedented increase of the EFTEM analysis throughput.
Network Pharmacology-Guided Development of a Novel Integrative Regimen to Prevent Acute Graft-vs.-Host Disease

Lapses in the graft-vs.-host disease (GVHD) prophylaxis and side effects of current standard care following allogeneic hematopoietic stem cell transplantation (allo-HSCT) call for novel regimens. Traditional approaches targeting T cells showed limited success in preventing acute GVHD (aGVHD). System medicine showed promising results treating complex diseases such as sepsis and multi-organ dysfunction syndrome (MODS). Adapting established network pharmacology analysis methods, we aimed to develop novel integrative regimens to prevent aGVHD. Our network pharmacology analysis predicted that Xuebijing injection (XBJ) targets a series of key node proteins in aGVHD network. It also unveiled that Salviae miltiorrhizae (Danshen), an herb in Xuebijing formula, which prevented aGVHD in rats, shares five out of six key GVHD node proteins targeted by XBJ. Interestingly, network pharmacology analysis indicated Xuebijing may share multiple aGVHD targets with Cyclosporin A (CsA), a first-line drug for preventing aGVHD in the clinic. Based on current information, we hypothesized that combination of XBJ and CsA may yield superior results in aGVHD prevention than either drug alone. We performed in vitro and in vivo assays to validate the predictions by the network pharmacology analysis. In vitro assays revealed XBJ prevented platelet aggregation and NF-κB nuclear translocation in macrophages. XBJ also promoted angiogenesis in tube-formation assay. Importantly, the combination of CsA and XBJ was effective in rescuing mice subjected to lethal GVHD. XBJ contributed to the rescue through preventing NF-κB nuclear translocation, attenuating inflammation and maintaining viability of macrophages. Overall, network pharmacology is a powerful tool to develop novel integrative regimens. Combination of XBJ and CsA may shed light on preventing aGVHD.
Clinical effects of repetitive transcranial magnetic stimulation combined with atomoxetine in the treatment of attention-deficit hyperactivity disorder

Objective To explore the effect of repetitive transcranial magnetic stimulation (rTMS) combined with atomoxetine (ATX) in the treatment of attention-deficit hyperactivity disorder (ADHD). Methods Sixty-four patients with newly diagnosed ADHD were enrolled from January 2016 to October 2017 from Psychological Centre for Adolescents and Children at 102th Hospital of People’s Liberation Army of China. These patients were randomly assigned to three groups according to treatment method: the rTMS group, the ATX group, and the rTMS+ ATX group. Before treatment and 6 weeks after treatment, clinical symptoms and executive functions of ADHD patients were evaluated with the Swanson, Nolan, and Pelham, Version IV (SNAP-IV) Questionnaire, continuous performance test, three subtests (arithmetic, digit span, and coding) of Wechsler Intelligence Scale for Children, as well as Iowa Gambling Tasks (IGT). The effects of treatment were compared among three groups. Results After 6 weeks of treatment, the scores of all factors in the SNAP-IV questionnaire were lower than those before treatment in the three groups; the scores of three subtests of Wechsler Intelligence Scale for Children, continuous performance test, and IGT were also significantly higher than those before treatment. The rTMS+ ATX group had a better improvement in attention deficits and hyperactivity impulse on the SNAP-IV questionnaire compared with the other groups, and also had a higher efficacy on cold and hot executive functions such as arithmetic, forward numbers, coding, and IGT. In addition, the ATX group performed better than the rTMS group in coding and IGT. Conclusion rTMS, ATX, and the combination therapy are effective in improving core symptoms and executive function in patients with ADHD. The combined treatment has significant therapeutic advantages over the single treatment groups. Compared with rTMS, the drug therapy has a better improvement in coding and IGT.