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    Supraclavicular lymph node incisional biopsies have no influence on the prognosis of advanced non-small cell lung cancer patients: a retrospective study

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    Abstract Background Supraclavicular lymph node (SCLN) biopsies play an important role in diagnosing and staging lung cancer. However, not all patients with SCLN metastasis can have a complete resection. It is still unknown whether SCLN incisional biopsies affect the prognosis of non-small cell lung cancer (NSCLC) patients. Methods Patients who were histologically confirmed to have NSCLC with SCLN metastasis were enrolled in the study from January 2007 to December 2012 at Guangdong Lung Cancer Institute. The primary endpoint was OS, and the secondary endpoints were complications and local recurrence/progression. Results Two hundred two consecutive patients who had histologically confirmed NSCLC with SCLN metastasis were identified, 163 with excisional and 39 with incisional biopsies. The median OS was not significantly different between the excisional (10.9\ua0months, 95% CI 8.7\u201313.2) and incisional biopsy groups (10.1\ua0months, 95% CI 6.3\u201313.9), P \u2009=\u20090.569. Multivariable analysis showed that an Eastern Cooperative Oncology Group (ECOG) performance status (PS) \u22652 (HR\u2009=\u20092.75, 95% CI 1.71\u20134.38, P \u2009<\u20090.001) indicated a worse prognosis. Having an epidermal growth factor receptor ( EGFR ) mutation (HR\u2009=\u20090.58, 95% CI 0.40\u20130.84, P \u2009=\u20090.004) and receiving systemic treatment (HR\u2009=\u20090.36, 95% CI 0.25\u20130.53, P \u2009<\u20090.001) were associated with a favorable OS. Neither the number (multiple vs. single) nor site (bilateral vs. unilateral) of SCLNs was associated with an unfavorable OS, and SCLN size or fixed SCLNs did not affect OS. Conclusions SCLN incisional biopsies did not negatively influence the prognosis of NSCLC patients. It was safe and feasible to partly remove a metastatic SCLN as a last resort in advanced NSCLC

    Endoscopy-assisted surgery for the management of benign breast tumors: technique, learning curve, and patient-reported outcome from preliminary 323 procedures

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    Abstract Background Endoscopy-assisted breast surgery (EABS), a technique that optimizes cosmetic outcome because it is performed through small wounds hidden in inconspicuous areas, could be an alternative surgical technique for benign breast tumors. In this study, we report the preliminary results of 323 EABS procedures performed at our institution for the management of benign breast tumors. Methods The medical records of patients who underwent EABS for benign breast lesions during the periods August 2010 to December 2015 were collected from the Changhua Christian Hospital EABS database. Data on clinicopathologic characteristics, type of surgery, hospital stay, and complications were analyzed to determine the effectiveness of the procedure for benign breast tumors. The operating time with the number of procedure performed was analyzed for learning curve evaluation. Patient satisfaction with cosmetic outcome was evaluated with a self-report questionnaire. Results A total of 323 EABS procedures were performed in 286 patients with benign breast lesions, including 249 (90.5%) patients with unilateral lesions. The mean age was 36\ua0years, the mean tumor size was 2.2\ua0cm, and the mean distance from the nipple to the tumor was 5.2\ua0cm. Most (93.8%, 303/323) of these tumors were excised through a transareolar wound, 2.4% (8/323) through an axillary wound, and 0.3% (1/323) through the infra-mammary fold. Histopathologic analysis revealed that 63.5% (202/318) of the tumors were fibroadenoma-related lesions. The mean operative time was 81.4\ua0min (59~89\ua0min), which was decreased with experience increased. The overall rate of complications was 6.5%, and all were minor and wound-related. Among the 110 patients who participated in the self-report cosmetic outcome evaluation, 85.4% reported being satisfied with the cosmetic result, and almost all were satisfied with breast symmetry. Of the patients interviewed, 92.7% reported that they would choose the same procedure if they had to undergo the operation again. Conclusions Our preliminary results show that transareolar video-assisted breast surgery is a safe and effective procedure with good cosmetic outcome and that it could be appropriate for patients with moderate to large peripherally located breast tumors. Trial registration CCH-IRB No.15115. Registered 14 December 2015 (retrospectively registered)

    Characterisation of microbial communities within aggressive prostate cancer tissues

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    Abstract Background An infectious aetiology for prostate cancer has been conjectured for decades but the evidence gained from questionnaire-based and sero-epidemiological studies is weak and inconsistent, and a causal association with any infectious agent is not established. We describe and evaluate the application of new technology to detect bacterial and viral agents in high-grade prostate cancer tissues. The potential of targeted 16S rRNA gene sequencing and total RNA sequencing was evaluated in terms of its utility to characterise microbial communities within high-grade prostate tumours. Methods Two different Massively Parallel Sequencing (MPS) approaches were applied. First, to capture and enrich for possible bacterial species, targeted-MPS of the V2-V3 hypervariable regions of the 16S rRNA gene was performed on DNA extracted from 20 snap-frozen prostate tissue cores from ten \u201caggressive\u201d prostate cancer cases. Second, total RNA extracted from the same prostate tissue samples was also sequenced to capture the sequence profile of both bacterial and viral transcripts present. Results Overall, 16S rRNA sequencing identified Enterobacteriaceae species common to all samples and P. acnes in 95% of analyzed samples. Total RNA sequencing detected endogenous retroviruses providing proof of concept but there was no evidence of bacterial or viral transcripts suggesting active infection, although it does not rule out a previous \u2018hit and run\u2019 scenario. Conclusions As these new investigative methods and protocols become more refined, MPS approaches may be found to have significant utility in identifying potential pathogens involved in disease aetiology. Further studies, specifically designed to detect associations between the disease phenotype and aetiological agents, are required

    Prosodic processing post traumatic brain injury - a systematic review

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    Abstract Background Traumatic brain injury (TBI) survivors often report difficulties with understanding and producing paralinguistic cues, as well as understanding and producing basic communication tasks. However, a large range of communicative deficits in this population cannot be adequately explained by linguistic impairment. The review examines prosodic processing performance post-TBI, its relationship with injury severity, brain injury localization, recovery and co-occurring psychiatric or mental health issues post-TBI Methods A systematic review using several databases including MEDLINE, EMBASE, Cochrane, LLBA (Linguistics and Language Behaviour Abstract) and Web of Science (January 1980 to May 2015), as well as a manual search of the cited references of the selected articles and the search cited features of PubMed was performed. The search was limited to comparative analyses between individuals who had a TBI and non-injured individuals (control). The review included studies assessing prosodic processing outcomes after TBI has been formally diagnosed. Articles that measured communication disorders, prosodic impairments, aphasia, and recognition of various aspects of prosody were included. Methods of summary included study characteristics, sample characteristics, demographics, auditory processing task, age at injury, brain localization of the injury, time elapsed since TBI, reports between TBI and mental health, socialization and employment difficulties. There were no limitations to the population size, age or gender. Results were reported according to the PRISMA guidelines. Two raters evaluated the quality of the articles in the search, extracted data using data abstraction forms and assessed the external and internal validity of the studies included using STROBE criteria. Agreement between the two raters was very high (Cohen\u2019s kappa\u2009=\u2009.89, P \u2009<\u20090.001). Results are reported according to the PRISMA guidelines. Results A systematic review of 5212 records between 1980 and 2015 revealed 206 potentially eligible studies and 8 case-control studies (3 perspective and 5 retrospective) met inclusion and exclusion criteria for content and quality. Performance on prosodic processing tasks was found to be impaired among all participants with a history of TBI (ages ranged from 8 to 70\ua0years old), compared to those with no history of TBI, in all eight studies examined. Compared with controls, individuals with a history of TBI had statistically significantly slower reaction time in identifying emotions from prosody and impaired processing of prosodic information that is muffled, non-sense, competing, or in conflict (prosody versus semantics). Heterogeneous findings on correlations between specific brain locations and prosodic processing ..

    Improved estimates for the triangle inequality

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    Abstract We obtain refined estimates of the triangle inequality in a normed space using integrals and the Tapia semi-product. The particular case of an inner product space is discussed in more detail. MSC: 46B99, 26D15, 46C50, 46C05

    First live records of the ruby seadragon (Phyllopteryx dewysea, Syngnathidae)

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    Abstract Until recently, only two species of seadragon were known, Phycodurus eques (the leafy seadragon) and Phyllopteryx taeniolatus (the common seadragon), both from Australia. In 2015, we described a new species of seadragon, Phyllopteryx dewysea (the ruby seadragon). Although the leafy and common seadragons are well known and commonly seen in aquarium exhibits world-wide, the ruby seadragon was known only from four preserved specimens, leaving many aspects of its biology unknown. Based on specimen records, it was speculated that the ruby seadragon normally lives at depths beyond recreational SCUBA diving limits, which may also explain why it went undiscovered for so long. The ruby seadragon also bears a superficial resemblance to the common seadragon, with a number of specimens misidentified in museum collections. The only recent live-collected specimen was trawled from the Recherche Archipelago, a cluster of over 100 islands in Western Australia. We took a small remotely operated vehicle (miniROV) to this locality to obtain the first images of live ruby seadragons. We made observations on the seadragon habitat and behavior, including feeding. We also provide new key observations on their morphology, notably that they lack dermal appendages and have a prehensile tail. We recommend that the ruby seadragon be protected as soon as practicable

    Protection via a ROM4 DNA vaccine and peptide against Toxoplasma gondii in BALB/c mice

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    Abstract Background Toxoplasma gondii ( T. gondii ) is an obligate intracellular protozoan parasite with a broad host range including most warm-blooded animals, including humans. T. gondii surface antigen 1 (SAG1) is a well-characterized T. gondii antigen. T. gondii expresses five nonmitochondrial rhomboid intramembrane proteases, TgROM1-5. TgROM4 is uniformly distributed on the surface of T. gondii and involved in regulating MIC2, MIC3, MIC6, and AMA1 during T. gondii invasion of host cells. Bioinformatics have predicted ROM4 B-cell and T-cell epitopes. Immunization strategy is also a key factor in determining the effectiveness of the immune response and has gained increasing attention in T. gondii vaccine research. In this study, we used a DNA prime-peptide boost vaccination regimen to assess the protective efficacy of various vaccination strategies using TgROM4. Methods We identified a polypeptide (YALLGALIPYCVEYWKSIPR) using a bioinformatics approach, and immunized mice using a DNA-prime and polypeptide-boost regimen. BALB/c mice were randomly divided into six groups, including three experimental groups (peptide, pROM4 and pROM4/peptide) and three control groups (PBS, pEGFP-C1 and pSAG1). Mice were then immunized intramuscularly four times. After immunization, IgG and cytokine productions were determined using enzyme-linked immunosorbent assays. The survival time of mice was evaluated after challenge with tachyzoites of T. gondii RH strain. Additionally, the number of cysts in the brain was determined after intragastric challenge with cysts of T. gondii PRU strain. Results Mice vaccinated with different immunization regimens (peptide, pROM4 and pROM4/peptide) elicited specific humoral and cellular responses, with high levels of IgG, IgG2a, and interferon (IFN)-\u3b3. Moreover, IgG, IgG2a and IFN-\u3b3 levels were highest in the pROM4/peptide group. Immunized mice, especially those in the pROM4/peptide group, had prolonged survival times after challenge with tachyzoites and reduced numbers of brain cysts after infection compared with negative controls. Conclusion A DNA prime-peptide boost regimen based on ROM4 elicited the highest level of humoral and cellular immune responses among immunization regimens, and may be a promising approach to increase the efficacy of DNA immunization

    Risk factors and clinical course of hungry bone syndrome after total parathyroidectomy in dialysis patients with secondary hyperparathyroidism

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    Abstract Background Hungry bone syndrome (HBS) is an important postoperative complication after parathyroidectomy for severe secondary hyperparathyroidism (SHPT). There is, however, little data in the literature on its detailed clinical course, and the associated risk factors remain controversial. Methods We did a single-center retrospective study on 62 consecutive dialysis patients who underwent total parathyroidectomy for SHPT to examine the risk factors, clinical course and outcome. Data on demographic characteristics, perioperative laboratory parameters including serum calcium, phosphate, alkaline phosphatase (ALP) and parathyroid hormone (PTH), drug treatment for SHPT and operative details of parathyroidectomy were collected. Results Seventeen (27.4%) patients developed severe postoperative hypocalcemia with HBS. The serum calcium dropped progressively while serum ALP rose after operation until 2\ua0weeks later when serum calcium reached the trough and serum ALP peaked. Serum phosphate also fell but stabilized between 4 and 14\ua0days. The total postoperative calcium and vitamin D supplementation was significantly larger, and hospital stay was significantly longer in the group with HBS as compared with those without HBS. Young age, high body weight, high preoperative ALP level, and low preoperative calcium level independently predicted the development of HBS while preoperative PTH and use of cinacalcet or paricalcitol did not. Conclusion HBS was common after total parathyroidectomy in patients with SHPT, and it is important to closely monitor the postoperative serum calcium, phosphate and ALP levels in the following 2\ua0weeks, especially for those at risk. The implications of our findings on perioperative management are discussed

    MALAT1 promoted invasiveness of gastric adenocarcinoma

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    Abstract Background Gastric cancer is the second leading cause of cancer globally, and the mechanism of its pathogenesis is still largely unknown. Recently, non-coding RNAs have been recognized to promote metastasis in various cancers, including gastric cancer. Methods We found that metastasis associated lung adenocarcinoma transcript-1 (MALAT1) is upregulated in gastric cancer tissue compared to adjacent normal tissue, as determined by microarray and subsequent qRT-PCR, then investigated the impact of MALAT1 on apoptosis, cell proliferation, and the cell cycle to dissect the carcinogenesis of gastric cancer, and examined mechanisms of invasion and metastasis. Expression of MALAT1 and U6 was determined by SYBR qRT-PCR in nine-teen gastric cancer cell lines and fifty fresh samples of cancer tissue and adjacent tissues. Downregulation of MALAT1 was accomplished with two different siRNAs. Cell proliferation was determined after treatment with these siRNAs. FACS using PI/Annexin-V staining was carried out. To analyze the invasiveness, a scratch wound-healing assay and a Matrigel invasion assay were performed. Cancer related gene expression assay was done after transfection of siR- MALAT1. Results The expression of MALAT1 was significantly elevated in various gastric cancer cell lines and gastric cancer tissues compared to normal cell lines and tissues ( p\u2009< \u20090.01). siR-MALAT1 significantly reduced viable AGS cell numbers and induced apoptosis ( p \u2009<\u20090.05). Deep invasion of tumor (advanced T stages) was more common in the high MALAT1-level group ( p \u2009=\u20090.039). siR-MALAT1 significantly decreased AGS cell invasiveness and migration. siR-MALAT1 reduced expression of snail and N-cadherin, and elevated E-cadherin. The Wnt/\u3b2-catenin related genes were significantly decreased by transfection of siRNA MALAT1. MALAT1 is involved in gastric carcinogenesis via inhibition of apoptosis and promotes invasiveness via the epithelial-to-mesenchymal transition. Conclusions In our study, we found that deregulation of MALAT1 could be involved in both tumorigenesis and invasiveness in gastric cancer cells

    Altered fractional amplitude of low frequency fluctuation associated with cognitive dysfunction in first-episode drug-na\uefve major depressive disorder patients

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    Abstract Background Previous studies have demonstrated that abnormities of both resting-state brain activity and cognitive dysfunction are frequently observed in patients with major depressive disorder (MDD). However, the underlying relationship between these two aspects is less investigated. In this context, the aim of the present study was to investigate the association between cognitive dysfunction and altered resting-state brain function in first-episode drug-na\uefve MDD patients. Methods Twenty-five drug-na\uefve MDD patients and twenty-six age-, sex-, and education-matched normal controls were recruited in this study. Cognitive function was evaluated by using a series of validated test procedures. The resting-state functional magnetic resonance imaging data were obtained on a Philips 3.0 Tesla scanner and analysed using the fractional amplitude of low frequency fluctuation (fALFF) method. Correlations of fALFF values with cognitive dysfunction were further analysed. Results Compared with healthy controls, MDD patients showed significantly fewer completed categories in the Wisconsin Card Sorting Test (WCST) and decreased scores in the first and second subtests of the Continuous Performance Test (CPT). However, the two groups did not differ in their performance on the Stroop Colour Word Test and Trail-making Test. MDD patients exhibited significantly decreased fALFF values in the left superior frontal gyrus (SFG), left middle frontal gyrus, and left inferior frontal gyrus, as well as increased fALFF values in the left inferior temporal gyrus (ITG), bilateral parahippocampal gyrus, and the right caudate. Finally, the correlation analyses revealed that fALFF values in the left SFG and left ITG were associated with the number of WSCT completed categories and scores on the second subtest of the CPT in MDD, respectively. Conclusions The present findings suggest that there is little evidence of an association between regional abnormalities in resting-state brain function and cognitive deficits in MDD

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