The Rhinosinusitis Disability Index (RSDI) is a validated measure of health-related quality of life (HRQL) in rhinitis. Responsiveness of the RSDI to changes in health status over time has not been described.We studied adults with a self-reported physician diagnosis of rhinitis identified through a national telephone survey. HRQL was assessed at baseline and at 24 months using the RSDI. Symptom severity, physical health status (SF-12 PCS), psychological mood (CES-D), and perceived control of symptoms were also assessed at the time of each interview. In addition, we ascertained specific health outcomes attributed to rhinitis, including days of restricted activity, job effectiveness, number of physician visits, and medication costs.Of 109 subjects interviewed at baseline, 69 (63%) were re-interviewed 24 months later. RSDI scores improved by = 0.5 standardized response mean in 13 (19%) subjects and worsened in 17 (25%). Change in the RSDI over time correlated with changes in symptom severity , physical health , mood  and perceived control of symptoms . In multivariate analyses adjusted for baseline health status, improvement in RSDI was associated with less restricted activity (p = 0.01), increased job effectiveness (p = 0.03), and decreased medication costs (p = 0.05), but was not associated with change in the number of physician visits from baseline (p = 0.45).The RSDI is responsive to changes in health status and predicts rhinitis-specific health outcomes. Rhinitis is a common chronic condition and can be a significant source of impairment. To measure the impact of rhinitis on health-related quality of life (HRQL), several disease-specific measures have been developed ,2. TheseThe Rhinosinusitis Disability Index (RSDI), another measure of HRQL, has been used both in persons with allergic disease as well as in those with chronic nasal obstruction ,6. The iperceived control'), can also play a large role in determining quality of life in rhinitis.In a previous analysis, we evaluated the performance of the RSDI cross-sectionally in 109 adults with predominately allergic disease . We founAlthough the discriminative properties of the RSDI have been studied in a cross-sectional fashion, its responsiveness to changes in health status has not been established. Responsiveness describes the ability of an instrument to capture meaningful changes in health over time. To demonstrate responsiveness, the same instrument must be administered at least twice over a given period of time. Responsiveness, however, differs from test-retest reliability. Test-retest reliability is measured by re-administering the same instrument within a short time interval during which the subject's health status remains unchanged. In contrast, responsiveness is typically demonstrated over longer intervals during which the subject's health status might reasonably have changed in some relevant way. Responsiveness has important implications for instruments used in clinical trials, where investigators are often trying to measure a clinically meaningful change before and after an intervention. In addition, it is also relevant in the study of disease progression or remission.To determine the responsiveness of the RSDI, we studied change in HRQL in 69 adults with rhinitis using data collected over a 24-month period. Cross-sectional results of the 109 subjects studied at baseline have previously been reported . ResponsWe used data collected as part of a prospective, longitudinal cohort study of adults with asthma and rhinitis. We assessed change in HRQL and health status among 69 subjects with rhinitis alone (without concomitant asthma) who participated in two consecutive interview waves conducted approximately 24 months apart. We evaluated responsiveness of the RSDI relative to other generic and disease-specific health status measures simultaneously assessed. We also evaluated how change in disease-specific HRQL, measured by RSDI, was related to change in other rhinitis-specific health outcomes, including restricted activity, job effectiveness, physician visits, and medication costs.Subject data were drawn from a larger prospective study of persons with asthma, rhinitis, or both. Details of recruitment and subsequent interview waves have been previously reported . In briewithout concomitant asthma. One hundred nine subjects completed the rhinitis component of our health survey at baseline, of which 69 (63%) were re-interviewed at follow-up.We used data from interviews conducted in 2000–1 (baseline for this study) and 2002–3 (follow-up for this study). Subjects were included in our analysis if they reported a physician's diagnosis of allergic rhinitis, sinusitis, hay fever, or chronic post nasal drip, To measure disease-specific HRQL in rhinitis, we used the RSDI, a 30-item questionnaire developed for use in persons with nasal or sinus disease . Each itTo measure symptom severity in rhinitis, we used four items drawn from a previously validated 31-item symptom scale for rhinoconjunctivitis and asthma developed by Wasserfallen et al . The speTo measure general physical functioning we used the physical component summary (PCS) of the SF-12. The SF-12 consists of 12 items drawn from the widely used Short Form 36 (SF-36). The reliability, validity, and responsiveness of the SF-12 have been demonstrated in various disease states, and are comparable to those of the SF-36 . SF-12 PThe CES-D consists of 20 items originally intended to assess depressive symptoms . Furtherperceived control, have been demonstrated to be an important correlate of health status, both in rhinitis and asthma [Psychosocial factors such as an individual's perception of his or her ability to deal with illness, referred to as d asthma ,14, as wd asthma . To measd asthma . SimilarOther rhinitis-specific health outcomes assessed included job effectiveness and restricted activity over the 4 weeks prior to interview, and physician visits and medication costs over the 12 months prior to interview. Job effectiveness, in terms of the specific impact of the subject's nasal condition, was assessed on a scale of 0 to 100% . Restricted activity was reported as the number of days restricted due to subject's medical condition. Physician visits were reported as the number of visits made specifically for a nasal condition, excluding routine visits for allergy desensitization. Out-of-pocket health costs were assessed separately for prescription and over-the-counter rhinitis medications. Subjects were asked to choose from four possible cost ranges: 'less than $10', '$10 to $99', '$100 to $1,000', or 'more than $1,000'. For the purpose of our analysis, we assigned subjects to the median value for each response category (e.g. $45 for '$10 to $99'), using $1000 for the highest category. A single cost variable was then calculated by summing costs for prescription and over-the-counter medications.t test for continuous variables, Chi-square test for dichotomous variables, and Chi-square test for trend for ordinal variables. Mean (±SD) summary scores were calculated for each health status measure at baseline and 24-month follow-up. Change was calculated by subtracting baseline scores from scores at follow-up and expressed as standardized response means (SRM). The SRM equates to the overall observed change divided by the standard deviation of the individual observed differences in score for the entire group. For the RSDI, a negative change in score reflects improved HRQL over time, whereas a positive change in score reflects worsened HRQL. To evaluate for changes in the RSDI within individuals, we used the paired t test.Comparisons between subjects who completed a follow-up interview (n = 69) with those who had not (n = 40) were made using t test to perform multiple comparisons (when ANOVA was significant at p < 0.05). We repeated this analysis for each health status measure to which the RSDI was compared .We examined responsiveness of the RSDI in two separate ways. First, we evaluated change in the RSDI score relative to change in the other health status measures delineated above , treating all variables as continuous. Pearson correlations were used to make these comparisons, as changes in scores approximated normal distributions for all health measures studied. As an alternative analysis, we categorized subjects into three groups, 'better', 'same', or 'worse', based on change in each health status measure. We used a change quantified as one standard error of measurement (SEM) or greater as the criterion for a difference great enough to be consistent with a minimal clinically important difference (MCID). Evidence by Wywrich and others supports use of one SEM  as an approximation of the MCID . By infeFinally, we used linear regression to evaluate the relationship between change in HRQL, as measured by the RSDI, and change in rhinitis-specific health outcomes . We first evaluated each health outcome in a bivariate model with change in RSDI score as the independent variable. We then performed multiple linear regression adding baseline RSS-4, SF-12 PCS, CES-D, and PCRQ as covariates in the model, in order to take into account each subject's health status at baseline. Effect estimates are expressed as change in the health outcome variable  per 1.0 SRM change in the RSDI score. All analyses were performed using SAS System for Windows release 8.02.Overall, the 69 subjects studied were predominately female, white (non-Hispanic), and well-educated, with predominately moderate to severe self-rated rhinitis Table . BaselinThe change in HRQL over follow-up approximated a normal distribution, with the majority of subjects demonstrating a change of less than 0.5 SRM Figure . The RSDChanges in symptom severity, physical functioning, mood, and perceived control also approximated normal distributions. Rhinitis symptom severity, as measured by the RSS-4, improved by a small, though significant, increment Table . The remChange in the RSDI at the individual level correlated moderately well with changes in the RSS-4, SF-12 PCS, CES-D, and PCRQ. Moreover, changes were in the anticipated directions Table . SpecifiWe reanalyzed these relationships, categorizing subjects based on change in health status as measured by the RSS-4, SF-12 PCS, CES-D, and PCRQ. Mean RSDI scores improved (negative change in score) in subjects categorized as 'better' with respect to symptom severity (RSS-4), physical functioning (SF-12 PCS), mood (CES-D), and perceived control (PCRQ)  Domains and Items.Click here for file


Chronic fatiguing illnesses, including chronic fatigue syndrome (CFS), pose a diagnostic and therapeutic challenge. Previous clinical reports addressed the utilization of health care provided to patients with CFS by a variety of practitioners with other than allopathic training, but did not examine the spectrum of complementary and alternative medicine (CAM) therapies used. This study was designed to measure CAM therapy use by persons with fatiguing illnesses in the United States population.During a random-digit dialing survey to estimate the prevalence of CFS-like illness in urban and rural populations from different geographic regions of the United States, we queried the utilization of CAM including manipulation or body-based therapies, alternative medical systems, mind-body, biologically-based, and energy modalities.Four hundred forty fatigued and 444 non-fatigued persons from 2,728 households completed screening. Fatigued subjects included 53 persons with prolonged fatigue, 338 with chronic fatigue, and 49 with CFS-like illness. Mind-body therapy  was the most frequently used CAM across all groups. Among women, there was a significant trend of increasing overall CAM use across all subgroups (p-trend = 0.003). All categories of CAM use were associated with significantly poorer physical health scores, and all but one  were associated with significantly poorer mental health scores. People with CFS-like illness were significantly more likely to use body-based therapy (chiropractic and massage) than non-fatigued participants . Use of body-based therapies increased significantly in a linear trend across subgroups of non-fatigued, prolonged fatigued, chronic fatigued, and CFS-like subjects (p-trend = 0.002). People with chronic fatigue were also significantly more likely to use body-based therapy  and mind-body (excluding prayer) therapy than non-fatigued participants .Utilization of CAM was common in fatiguing illnesses, and was largely accounted for by the presence of underlying conditions and poor physical and mental health. Compared to non-fatigued persons, those with CFS-like illness or chronic fatigue were most likely to use body-based and mind-body therapies. These observations have important implications for provider education programs and development of intervention strategies for CFS. Chronic fatiguing illnesses present diagnostic and management challenges for health care providers. Chronic fatigue syndrome (CFS) is a complex illness characterized by medically and psychiatrically unexplained disabling fatigue that is not relieved by rest and is accompanied by symptoms of prolonged postexertional malaise, unrefreshing sleep, impaired concentration and short-term memory, muscle or joint pain, headache, sore throat and tender lymph nodes . In popuAlthough not all persons suffering from CFS seek allopathic care ,7, standWe examined the use of CAM categories and conventional medicine in a cross-sectional population survey of fatiguing illnesses in the United States and evaluated variables associated with their utilization Specifically we asked the following questions: (i) Do CFS-like and otherwise fatigued subjects use CAM and, if so, is it used more or less frequently than non-fatigued persons; (ii)Which modalities do they use; iii) What effects do demographic and geographic factors have on the association of CAM use and fatigue classification; (iv) Do the presence of accompanying/underlying illness and impaired health in general affect the use of CAM; (v) What conclusions can we make from the available data on CAM use by fatigued individuals that could be potentially useful to providers in their management of fatigued persons?This study adhered to human experimentation guidelines of the U.S. Department of Health and Human Services and the Helsinki Declaration. The CDC Human Subjects committee approved study protocols. All participants were volunteers who gave informed consent.Data were collected during a random-digit dialing survey to estimate the prevalence of fatiguing illnesses in urban and rural populations from different geographic regions of the United States between July 2001 and January 2002 as detailed in Bierl et al.. In brieWe conducted standardized detailed telephone interviews with household residents between 18 and 69 years of age who the informant identified as fatigued ≥ 1 month, and with a random sample of non-fatigued (NF) residents identified in the screening interview. The detailed interview ,5 requirSince this study was formulated in 1999, we used as an operational definition the CAM modalities initially addressed by Eisenberg et al.,  as assigIndividuals reporting fatigue lasting between one and 5-months were classified as having prolonged fatigue (PF); those with ≥ 6 months of fatigue were classified as having chronic fatigue (CF); and persons without fatigue for one month were considered as non-fatigued (NF). We classified chronically fatigued respondents as having a CFS-like illness if their fatiguing illness met criteria of the 1994 CFS research case definition [This study analyzed the use of the 5 CAM categories (described above) by various groups of fatigued  and NF subjects and examined the effect of various covariates on this relationship. For the purpose of analysis, race was categorized as White, Black and Other, geographic region was categorized as Northeast, South, West, or Midwest and rural and urban areas were analyzed separately. Education was categorized as <high school, high school graduate, some college or post-high school training, college graduate and post-graduate. Information on categorical household income was collected and treated as a dichotomous variable of ≤$40,000, >$40,000 based on the US median income. Physical and mental health scores, as measured by the SF-12, were treated as continuous measures. Other medical/psychiatric conditions were treated as counts in the analysis.All statistical analyses were conducted in SAS version 9.0 . We compared categorical variables between study groups by using either Chi-square or Fisher's exact tests and compared continuous variables between study groups by using either the T-test or the Wilcoxon rank-sum test. Correlations between continuous variables were computed using the Pearson Correlation Coefficient. We used separate multinomial logistic regression models (PROC GENMOD) to compute odds ratios (OR) as estimates of risk of CAM use among participants with various categories of fatiguing illness compared to the NF group. Dependent variables in these models included the following CAM categories: body-based, alternative medicine systems, mind-body including prayer, mind-body excluding prayer, biologically-based, and energy. All regression models included adjustment for age (continuous), sex, and count of other medical or psychiatric conditions. Additional covariates were included if they had p-values < 0.05 . We further examined the effect of general physical and mental health on the adjusted ORs for the associations of fatigue case status and CAM categories by including the SF12 scores for physical and mental health in the regression models. We computed 95-percent confidence intervals (95% CI) to measure the precision of the ORs. We evaluated trend in ORs across a gradient of fatiguing illness categories by using separate logistic regression models for each CAM outcome and assigning values of 1–4 to a categorical variable representing study groups , adjusting for covariates. Wald test was used to calculate p-values for trend (p-trend). As is standard practice in regression models, subjects with missing values for any independent variable in a regression model were excluded from that specific analytic model.Four hundred forty fatigued people and 444 non-fatigued (NF) respondents completed the full interview. Eligibility and refusal rates were similar for the two groups . Fifty-tOverall, 77% of participants reported using some CAM therapy in the 12-month period prior to the interview. Use of any CAM modality (i.e. ever in the preceding 12 months) was reported more frequently among women (56.8%) than men (44.2) p = 0.0003), and increased significantly with increasing level of education (p-trend < 0.0001). Reported use of any CAM modality did not significantly vary by age, race, income or geographic regions  reported having various medical or psychiatric conditions than the non-fatigued participants (38.5%) (p < 0.0001). None of these conditions were exclusionary according to the definition of CFS (1). The most commonly reported, but not verified, co-morbid diagnoses in the study population were: hypertension (13%), diabetes mellitus of unknown type (10%), thyroid disease (8%), asthma (8%), depression (7%), fibromyalgia (6%), hyperlipidemia (4%), cardiovascular disease (4%) and identifiable sleep disorders such as apnea and narcolepsy (<2%).We examined the association of any CAM use with the presence of a medical or psychiatric condition. Among the NF and PF groups, similar proportions of those who did and did not report any CAM use had a medical/psychiatric condition . However, among the CF group and CFS-like group, significantly higher proportions of those who reported any CAM therapy use had a medical/psychiatric condition, compared to those who did not use any CAM . The mean number of medical/psychiatric conditions increased steadily across study groups, ranging from an average of 0.65 among the NF group to 1.8 among the CFS-like group (p < .0001).We also explored whether use of CAM was associated with physical and mental health status, as measured by the SF-12. Non-fatigued subjects had scores comparable to published norms . Since fOverall, 37.5% of all respondents said that they discussed their CAM therapy use with their physician, but this practice increased across subgroups, ranging from a frequency of 26.1% among the NF subgroup to 57.6% among the CFS-like group (p-trend = 0.0001). Individuals previously diagnosed with CFS reported more CAM therapy use than other persons with fatigue who were not diagnosed with CFS.Odds ratios for use of body-based therapy increased in a significant trend across fatigue categories of PF, CF and CFS-like subjects (p-trend = .0003) Table . NotablyThe CFS-like group was also 2.9-times more likely to report using an alternative medical system (represented by homeopathy) compared to the NF group after adjusting for age, sex, education and census region ; there was also a significant trend of decreasing ORs associated with homeopathy use across study groups (p-trend < .0001) Table . After fMind-body CAM use was not reported significantly more often by any of the fatigue groups compared to the NF group Table . HoweverWe further examined whether the associations of body-based CAM and mind-body (excluding prayer) CAM use with CFS-like illness and chronic fatigue, respectively, could be accounted for by physical or mental health. SF-12 scores for physical health and mental health were significantly but weakly correlated , allowing for their simultaneous addition to the fully adjusted models predicting use of these CAM categories. Physical health remained significantly and independently associated with use of body-based CAM (p = 0.002) after consideration of illness group and other covariates. Mental health remained significantly and independently associated with use of the mind-body CAM (excluding prayer) (p = 0.003). However, after accounting for the effects of physical and mental health scores, the association between CFS-like illness and body-based CAM use was attenuated and no longer statistically significant . The association of CF illness and mind-body (excluding prayer) CAM was no longer detected .Our study addressed the use of complementary and alternative medicine (CAM) therapies identified in the 1990's by persons with fatiguing illnesses and non-fatigued persons. As defined here, 77.0% of subjects reported CAM use between July 2001 and January 2002, a greater proportion than that previously reported at the national level, where in general it ranged from 36% in 1990, to 46% in 1997, and 62% in 2002 -13. The Compared to the non-fatigued group, persons classified as having CFS-like illness and those classified as having chronic fatigue were significantly more likely to use only the body-based CAM therapy category, which includes chiropractic and massage therapies. We also found that compared to the NF group, frequency of use of body-based therapy by subjects with fatigue increased across groups of PF, CF and CFS-like in a linear trend.After excluding use of personal prayer and prayer by others, use of other components of the mind/body category was reported significantly more often by the chronic fatigue group compared to the non-fatigued group. However, the ORs associating use of these and other CAM categories were substantially attenuated when we adjusted for the number of other, non-exclusionary medical/psychiatric diagnoses. Further adjustment for physical and mental health, as measured by scores on the SF-12, further diminished these associations and resulted in their non-significance. Taken together, these data suggest that both the presence of "other diagnoses" and poorer physical and mental health account for some of the use of body-based and mind-body CAM therapies by persons with CFS-like illness and CFS.Pearson et al.  identifiIn the general population, CAM therapies were used as adjuncts to standard care, health promotion, or disease prevention . AlthougInterpretation of our results must take into consideration the limitations of this study. We classified subjects based on telephone interviews with the inherent problems of under-representation of low income, and transient populations, and did not conduct in-person interviews, physical examinations or laboratory tests to rule out other conditions associated with fatigue. It is known that approximately 20% of those diagnosed with CFS or CFS-like illness have other conditions that are exclusionary for the diagnosis of CFS , so it iOn a practical note, physicians see and classify these patients and must know about their use of CAM in order to plan or modify their evaluation, diagnosis, and treatment strategy. Understanding the patients' rationale for CAM therapy and their perception of its efficacy may provide information on whether symptoms or the illness dictate intervention and on positive or negative consequences of CAM therapy ,24. FurtCAM use in fatiguing illness is more prevalent than it is in non-fatigued persons. Body-based therapies (chiropractic and massage therapy) and mind-body (excluding prayer) therapies were significantly more likely to be used by persons with chronic fatigue or CFS-like illnesses, compared to non-fatigued controls. However, poorer physical and mental health and the presence of other physical and psychiatric conditions, appear to account for greater use of these CAM therapies by persons with chronic fatigue and CFS-like illness.The author(s) declare that they have no competing interests.JFJ, ABJ, and WCR designed the study. JFJ, ABJ, EM, and RB identified the questions to be analyzed in the report. EM and RB performed the statistical analyses. All authors contributed to writing the report and have read and approved the final manuscript.The pre-publication history for this paper can be accessed here:


The internet is the (current) ideal medium for sharing simple data: but the tools for describing complicated datasets, and the ethics and resulting technology for sharing confidential data are less well understood.I first describe a simple dataset we've put on the web - some of the world's first genome screen data. The data is anonymous; there was full subject consent; there is no foreseeable subject harm/benefit from data release; and the data sets are in a form readily understood by scientists working in the field. I then describe a large-scale longitudinal epidemiological study, and the tools used to make this comprehensible to secondary data users - the main innovation being a searchable data dictionary and interactive decision support for selecting data subsets from the multi-thousand variable whole. Thirdly I describe the current data access arrangements - "good enough" anonymity, and ftp access for signed-up collaborators. Lastly I describe fully-functioning experimental alternatives: aggregated tables (generated with reference to the data dictionary) and raw data access for named collaborators via encryption, the web's HTTPS protocol using Secure Socket Layers.Datasets can be shared via the Web, however complex or confidential. For a simple (but important) dataset, see: http://www.mrc-bsu.cam.ac.uk/MSgenetics/ . For a complex dataset and support tools, see: http://www.mrc-bsu.cam.ac.uk/cfas/ or https:// www.mrc-bsu.cam.ac.uk/cfas/. This currently uses US-export (i.e. weak) levels of encryption.There is increasing pressure  to share data collected during publicly-funded medical research. While the social sciences have shared data for many years via archive sites, "patient confidentiality" has prevented it in the medical world. Ironically, the increased use of biological samples- which require far greater stress on confidentiality and the anonymity of public records - have led to proposals for public databases of, and potential competition for, these scarce, expensive resources. For social sciences, record anonymisation is the stripping of identifiers, but they also rely on the fierce legalese of "undertaking forms" to prevent subject identification. This model is breaking down with linked genotypic/phenotypic data - where it might become hugely financially worthwhile to identify a study subject. The data dictionary approach - adopted as an aid to understanding a large complex dataset, can also be used to generate anonymised subsets of the data, and aggregated tables live on the Web. However, full access will require the newer, secure web protocols - if we can find the political and financial will to buy it in from the States.


The anti-viral function of RNA silencing was first discovered in plants as a natural manifestation of the artificial 'co-suppression', which refers to the extinction of endogenous gene induced by homologous transgene. Because silencing components are conserved among most, if not all, eukaryotes, the question rapidly arose as to determine whether this process fulfils anti-viral functions in animals, such as insects and mammals. It appears that, whereas the anti-viral process seems to be similarly conserved from plants to insects, even in worms, RNA silencing does influence the replication of mammalian viruses but in a particular mode: micro(mi)RNAs, endogenous small RNAs naturally implicated in translational control, rather than virus-derived small interfering (si)RNAs like in other organisms, are involved. In fact, these recent studies even suggest that RNA silencing may be beneficial for viral replication. Accordingly, several large DNA mammalian viruses have been shown to encode their own miRNAs. Here, we summarize the seminal studies that have implicated RNA silencing in viral infection and compare the different eukaryotic responses. They direct a multi-component complex, the RNA-induced silencing complex (RISC), on a targeted mRNA harbouring sequence-homology. RISC invariably contains some Argonaute (Ago) family member proteins, such as Ago2 in human [RNA silencing is often considered as a potent nucleic acid-based immune system. In fact, invading nucleic acids can be recognised by some cells as undesirable, by a mechanism that is not yet totally unravelled, and are silenced by a process based on 21–25 nt long small RNAs. A now classical example of this phenomenon was provided more than ten years ago by experiences performed on transgenic petunias  and wormin human , that prin human , whereinArabidopsis thaliana) [et al., have shown that the replications of CMV-Y and TMV were not affected in plants impaired in DCL-1 and DCL-3 functions, likely suggesting that DCL-4 functions as a component of the anti-TMV and anti-CMV silencing [Several observations from plant virologists converged to the idea that RNA silencing was an efficient anti-viral system. The first evidence probably came with the finding that plant viruses trigger the silencing of endogenous mRNAs sharing sequence-homology. For instance, the phytoene desaturase (PDS) mRNA was easily silenced upon replication of the Tobacco mosaic virus (TMV) harbouring a stretch of PDS . This lehaliana) . The Dicilencing . At thatilencing ) a situailencing . In factilencing ,19.planta [An indirect proof that RNA silencing constitutes an efficient anti-viral system was also provided by the discovery of virus-encoded suppressors of silencing. The observation of an accentuation of symptoms induced by one virus by co-infection with a second and unrelated virus, a phenomenon called synergism, provided the first hint for virus-mediated silencing suppression . The Potplanta . The cryplanta ,29. Therplanta .The capacity of plant RNA silencing to be amplified and to propagate in the whole organism likely represent two additional layers that ensure its efficacy against viruses . The plaFrom those studies, we may consider that the demonstration that a non-plant virus is restricted by RNA silencing requires three experimental observations: (i) presence of virus-derived siRNAs, illustrating the onset of RNA silencing, (ii) production of a virus-encoded silencing suppressor, as a mechanism to escape these virus-derived siRNAs and (iii) silencing movement in the infected host, which may be an indirect hint for the efficiency of anti-viral silencing.Drosophila S2 cells infected with the Flock House Virus (FHV), member of the Nodaviridae family [et al., reported the accumulation of virus-derived siRNAs in FHV-infected S2 cells. The viral accumulation was further found to be enhanced in cells depleted for the AGO2 protein, a crucial component of the RISC complex, as mentioned above [in vitro [et al., reported an RdRp activity in Drosophila embryonic extracts [Drosophila genome. More important, using transgenes expressing dsRNA in adult fly, Roignant et al., have conclusively demonstrated that transitive RNA silencing does not occur in Drosophila and that it remains strictly confined within the cells where it as been elicited [Drosophila genome to domesticate endogenous and mobile genetic elements. Jensen et al., reported that transpositional activity of the I element, a transposon similar to mammalian LINE elements, can be repressed by prior introduction of transgenes expressing a small internal region of the I element [et al., reported that the endogenous retrovirus gypsy is silenced in fly ovaries by the action of one argonaute protein and that ovary cells naturally accumulate gypsy-derived small RNAs [Many arthropod species have been found to support artificially induced RNA silencing, among which fruit flies  and mosqe family . Li et aed above . Determied above . Recent in vitro ,43. Secoin vitro . Althougextracts , no membelicited . Thus, t element . This reall RNAs . RNA silall RNAs . Hence, Caenorhabditis elegans by a mechanism related to RNA silencing. Sijen et al., detected dsRNAs and siRNAs derived from diverse regions of the Tc1 transposon and showed that a germline-expressed reporter gene, fused to a stretch of the Tc1 sequence, is silenced in a manner dependent on essential silencing components [Drosophila, RNA silencing moves in worm. In a shaping study wherein they demonstrated that dsRNA is the key elicitor of RNA silencing, Fire et al. also reported that injection of dsRNA into the body cavity or gonad of young adults produced gene-specific interference in somatic tissues of the injected animal [C. elegans genome contains 2 RdRp genes, termed ego-1 and rrf-1, mandatory for RNA silencing in germline and somatic tissues, respectively [et al., reported that mRNA targeted by RNA silencing functions as a template for 5' to 3' synthesis of new dsRNA [sid (systemic RNAi defective) [rsd (RNAi-spreading defective) [sid-1/rsd-8, encoding a multispan transmembrane protein essential for systemic but not cell-autonomous RNAi [et al., further demonstrated that SID-1 facilitates the passive cellular uptake of preferentially long dsRNAs using Drosophila S2 cells [Transposable elements are also tamed in mponents . Cloningmponents . As mentd animal . The C. ectively ,52. Howeew dsRNA . This effective)  and rsd fective) . Both grous RNAi ,55. FeinS2 cells . InteresS2 cells .C. elegans [et al., showed that the nematode N2 cells do support the replication of the mammalian Vesicular Stomatitis Virus (VSV) [C. elegans, seems to inhibit RdRP-directed siRNA amplification, and worms with mutations in rrf-3 are more sensitive to RNA silencing induced by dsRNAs [eri-1 mutants, resulting in enhanced gene suppression [et al., observed virus-specific 20–30 nt long small RNAs [et al., showed complete replication of FHV in worm strains carrying integrated transgenes coding for full-length cDNA copies of FHV genomic RNAs [C. elegans is able to respond to viral infection by generating virus-derived siRNAs may indicate that the complexity of the silencing pathways  is not a prerequisite for the existence of anti-viral RNA silencing.  This is particularly important when investigating the potential anti-viral role of silencing in mammals, which, like worms, encode only one Dicer. However, we cannot yet exclude that the complexity of the silencing pathway is ensured by the diversity of the Argonaute proteins found in worm [In nematodes, the mechanism of transposon taming and the movement of RNA silencing together suggest that silencing is implicated in anti-viral defence. However, asking whether silencing is involved in worm anti-viral defence is complicated by the absence of worm-specific viral pathogens . Noneth elegans ,59. Wilky dsRNAs . ERI-1, pression . Decisivmic RNAs . The antmic RNAs . The fac in worm .We can now assume that anti-viral RNA silencing exists in plant, insect and nematode, even if the question as to know whether it is a natural and efficient anti-viral response in invertebrates remains opened. For that reason, several laboratories were prompted to investigate the potential contribution of RNA silencing in the replication of mammalian viruses.The Tusch1 lab first attempted to clone virus-derived siRNAs from cells infected with various viruses . They neBy our side, we also started working on the contribution of RNA silencing in mammalian anti-viral response, using the prototypic foamy retrovirus, the Primate Foamy Virus type 1 (PFV-1), as a model . This coThe anti-viral effect of miR-32 was not linked to a potential implication of its unknown cellular target because a mutant carrying point mutations, that disrupt the hybridization of the cellular miRNA with the viral mRNA, accumulated to higher level than the wild type virus . This obet al., that gene therapy viral vectors containing a miRNA target exhibit a tissue-specific expression according to miRNA expression levels support this proposal [Cellular miRNAs are implicated in fundamental biological processes, such as cellular differentiation for instance, therefore, each cell type is thought to harbour a particular miRNA repertoire . In thatproposal . Besidesproposal , raisinget al., have shown that simian foamy viruses might have co-speciated with their Old World primate hosts for at least 30 million years [Viral genomes have alas the capacity to rapidly and non-randomly evolved, notably to counteract therapeutic strategies and to settle in new cellular contexts. Nonetheless, it appears that PFV-1 have conserved the viral target of miR-32, suggesting that PFV-1 may hijack the miR-32, for instance, to decrease viral protein expression during the latent stage of infection -90. In lon years . A recenon years . They deon years . The auton years . Anotheron years . Thus, cenv gene [To escape this miRNA-based 'innate' form of immunity, we additionally showed that PFV-1 encodes a suppressor of silencing, Tas, that have the capacity to inhibit miR-32 action . Tas exeenv gene ,99. In cenv gene -101. Intenv gene , likely env gene . The Infenv gene -105. Morenv gene . Severalenv gene ,102,107.An alternative strategy to escape cellular miRNAs could be to introduce synonymous mutations in the viral genome that would disrupt the cellular miRNA/viral target hybrid. This hypothesis may be suitably applied to high mutation rate viruses. In fact, this particular type of RNA silencing evasion has already been described for HIV and HCV when artificially targeted by synthetic siRNAs -110. As Recent evidences support a role for RNA silencing in the replication of mammalian viruses but its consequences remain to be clarified as to know whether it is positively required for replication or if, conversely, it constitutes a crucial host defence system. To date, only miRNA molecules, either encoded by the host or by the virus itself, have been implicated, with the notable exception of one discret HIV-derived siRNA duplex produced during the course of infection and able to cleave Env mRNA . The modFinally, long dsRNAs typically used to elicit RNA silencing in other organisms potently activate a specific mammalian cell defence mechanism, the Interferon (IFN) Response  (for revThe author(s) declare that they have no competing interests.AS and CHL participated to the conception, design and writing of the article.


Schistosoma infection in school-aged children (SAC) is associated with educational loss and cognitive deficits.By means of meta-analysis of information from all relevant epidemiologic studies, we examined the hypothesis that Schistosoma infection and cognitive or educational outcomes. Cognitive function was defined in four domains—learning, memory, reaction time, and innate intelligence. Educational outcome measures were defined as attendance and scholastic achievement. Risk of bias (ROB) was evaluated using the Newcastle-Ottawa quality assessment scale. Standardized mean differences (SMD) and 95% confidence intervals (CI) were calculated to compare cognitive and educational measures for Schistosoma infected /not dewormed vs. uninfected/dewormed children. Sensitivity analyses by study design, ROB, and sequential exclusion of individual studies were implemented. Thirty studies from 14 countries, including 38,992 SAC between 5–19 years old, were identified. Compared to uninfected children and children dewormed with praziquantel, the presence of Schistosoma infection and/or non-dewormed status was associated with deficits in school attendance , scholastic achievement , learning  and memory  tests. By contrast, Schistosoma-infected/non-dewormed and uninfected/dewormed children were similar with respect to performance in tests of reaction time  and intelligence . Schistosoma infection-associated deficits in educational measures were robust among observational studies, but not among interventional studies. The significance of infection-associated deficits in scholastic achievement was sensitive to ROB. Schistosoma infection-related deficits in learning and memory tests were invariant by ROB and study design.This review was prospectively registered in the PROSPERO database (CRD42016040052). Medline, Biosis, and Web of Science were searched for studies published before August 2016 that evaluated associations between Schistosoma infection/non-treatment was significantly associated with educational, learning, and memory deficits in SAC. Early treatment of children in Schistosoma-endemic regions could potentially mitigate these deficits.CRD42016040052ClinicalTrials.gov  Schistosoma treatment is currently uncertain, despite the recommended practice of wide-scale deworming with praziquantel. We addressed this knowledge gap by synthesizing information from 30 relevant epidemiologic studies reporting on 38,992 children between 5–19 years old from 14 countries. In those studies, Schistosoma infection or non-dewormed status was associated with educational loss and cognitive deficits. Specifically, there were small to moderate deficits in both school attendance and scholastic achievement. Similarly, Schistosoma infection or non-dewormed status was associated with deficits in learning and memory domains of psychometrically tested cognitive function. However, there was no evidence of Schistosoma infection- or non-deworming-associated deficits on tests of innate intelligence or reaction-time. Overall, compared to Schistosoma-uninfected or to dewormed children, the presence of Schistosoma infection or non-dewormed status was associated with educational, learning, and memory deficits in school-aged children. The combined evidence suggests that early treatment of children in Schistosoma-endemic regions could mitigate these deficits.Empirical evidence for cognitive or educational benefits of anti- Schistosoma parasites–S. mansoni, S. haematobium, and S. japonicum , one study was conducted in St. Lucia (Caribbean), and another study was implemented in Madagascar.S. haematobium (20 studies), S. japonicum (3 studies), or S. mansoni (10 studies)). These infected children were compared to 13,835 (40.6%) children without Schistosoma infection. A total of 2,366 children were studied in the context of randomized intervention studies including praziquantel vs. placebo, or prospective treatment studies that included baseline and follow-up assessments of cognitive function (Table 2). Of the 30 studies included in this review, three (10%) and 16 (53.3%) were judged to be at very high or high risk of bias, respectively, per the NOQAS (Table 3).A total of 36,626 children were studied in the context of cross-sectional or case control studies. Of these, cognitive test scores and/or indicators of educational loss were measured in 23,126 (59.3%) children infected with one of three schistosomiasis species (Schistosoma infection-related differences in school attendance (Table 2). Schistosoma infection-associated attendance deficits varied in magnitude and direction by study design. Specifically, we did not find any evidence of association between Schistosoma infection and school attendance among the two interventional studies ; however, the observed infection-associated deficit in school-attendance was robust for the pooled estimate of 14 observational studies . Compared to uninfected or praziquantel-treated children, the magnitude and direction of infection-associated deficit in school attendance was similar for children infected with S. haematobium or S. mansoni. Within strata of study quality, the association between infection and scholastic achievement was directionally consistent and statistically robust (Table 4). Across all studies, regardless of design or ROB, a deficit in school-attendance was evident for Schistosoma-infected or non-praziquantel-treated children compared to uninfected or praziquantel treated children .Sixteen studies evaluated Tables  and 4. Specifically, achievement deficit with Schistosoma infection was noted in the pooled estimate derived from four intervention studies, but the magnitude of this association was lower and not statistically robust . Compared to uninfected or PZQ-treated children, the infection or non-treatment associated deficit in scholastic attainment was directionally consistent across different Schistosoma species, although the magnitude of effect was higher for infection with S. haematobium  than for infection with S. mansoni . Among observational study designs, scholastic achievement deficit was statistically robust and of larger magnitude . Similarly, Schistosoma infection was not associated with deficits in scholastic achievement among studies identified as low risk of bias . The estimates of infection-related deficit in scholastic achievement increased when study quality was lower: for studies with high risk of bias (n = 7) the SMD = -0.84 ; for studies with very high risk of bias (n = 7) SMD = -0.92 95% CI: -2.1, 0.28) although the estimated difference was statistically imprecise  among the studies with greatest risk of bias.The overall finding of schistosomiasis-associated achievement deficit  was directionally consistent but varied in magnitude by study design and study quality Schistosoma infection-associated deficits in memory tests  and observational studies  were not statistically robust. For Schistosoma infection-related association with learning, pooled estimates suggested the presence of deficits for infected/non-dewormed vs. uninfected/praziquantel-treated children . However, the magnitude of this association differed according to study design. Here, larger pooled standardized differences were realized for interventional studies  than for observational studies . Schistosoma infection was not significantly associated with performance on tests of reaction time  or performance in tests of innate intelligence . For all psychometrically-assessed cognitive domains, the overall findings were not sensitive to study quality. Of note, the majority of publications with psychometrically-evaluated endpoints had low risk of bias and produced pooled estimates similar in magnitude and direction to the overall results (Table 4).We found 2 ≥ 74.8%; Tables 4) for all outcome measures, but there was no evidence of undue influence by individual studies or of publication bias among the included studies , to the exclusion of individual studies (S2 Table), or to the influence of publication year .High levels of heterogeneity were observed across included studies , c) we further defined domains of cognitive function based on psychometrically-assessed testing to include the following: learning, memory, attention, and intelligence and d) the intervention, as defined in this meta-analysis, denoted treatment for Schistosoma infection, whether or not the study was randomized.Prior meta-analysis of four randomized controlled trials that evaluated cognitive impacts of STH infections–which sometimes co-occur with schistosomiasis, have reached a different conclusion about the cognitive and scholastic effects of STH infection and the impact of interval treatments for STH , 26. ThoSchistosoma infection-related differences in cognitive and educational outcomes. The inclusion of all available evidence reflects current standards for clinical evidence-gathering to inform health policy, in order to shape clinical practice based on the ‘best available’ relevant information [Schistosoma infection is an exposure affecting millions of children in endemic regions. Hence, small to moderate deficits at the individual level may amount to large and important differences in disease burden at the population level [Schistosoma infections to respective outcomes, and the expected benefit of systematically lowering infection-related deficits in the millions of children at risk.We intentionally included data from all available epidemiologic studies–whether interventional or observational in design, in this first systematic review and meta-analysis of ormation , 24. Futon level , 74. Oura priori exclusion of observational studies in systematic reviews is inappropriate and inconsistent with the evidence-based medical decision-making approach [As a limitation of our approach, we acknowledge the possibility of residual confounding and bias in the primary literature, given that majority of included studies were observational or non-randomized intervention trials. Only two of the 30 included studies used an RCT design, thus a sensitivity analysis based on RCT vs. non-RCT study design was not possible. However, as part of sensitivity analysis we evaluated the potential for differences in pooled estimates based on our expanded definition of intervention as including longitudinal studies that included praziquantel treatment. Investigation of pooled estimate sensitivity by region of study, the year of publication, and by risk of bias did not result in materially different statistical inferences. Specific investigation of publication bias suggests that any possible greater likelihood of publishing positive studies did not unduly influence observed findings. Our approach of including both interventional and non-interventional studies is consistent with theoretical and empirical evidence that meta-analyses based on observational studies generally produce estimates of effect similar to those from meta-analyses based on randomized controlled trials, and that approach , 76. In S1 Table) to provide a basis for further discussion and give sufficient context for critical evaluation of our approach in developing future studies.Despite the intuitive appeal of our cognitive domain based evaluation, we acknowledge the critique that our classification of psychometric instruments by domain required some level of subjectivity, especially for tools that capture performance across multiple domains. We explicitly identified the instruments used in each study and, based on literature description of the major cognitive domain assessed by each tool, combined related tools into four separate domains. Ultimately, each instrument was assigned to one cognitive domain only. We have described the logic for our choices in the supplementary information  is a strength of our empirical approach. By so doing, we recognize that Schistosoma spp. infection in children. The ‘small-to-moderate’ effects demonstrated may, in reality, be an underestimate of the lifetime impact of Schistosoma infection on personal performance . Typical epidemiologic studies necessarily include only a constrained portion of the relevant etiologic period. Among school-age children, Schistosoma infection is often effectively already chronic and/or recurrent, with reinfection rates extremely high in the absence of meaningful environmental interventions to reduce re-infection following treatment. The cumulative cognitive and educational impact of persistent infection may not be adequately captured by the relatively short-term investigations of treatment impact included in this meta-analysis.The finding of infection-related cognitive deficits and educational loss reported here is clinically and health policy-relevant for mitigating the cognitive and functional morbidities of -endemic regions, many children are infected by age two and remain chronically infected through school-age and late adolescence [Schistosoma control treatment guidelines, preschool-age children are not treated as part of routine deworming programs for STH or schistosomiasis [Schistosoma infection in preschool children [Schistosoma infection on cognitive/educational domains would be a major justification for expanding the age-bracket of children who should be treated with praziquantel. Currently, evidence suggests that the timing of infection across a life path is especially consequential in terms of the severity of cognitive and physiologic impairments experienced [Schistosoma infection will be important for understanding the magnitude of potential impact of better prevention of Schistosoma infection.In schistosomiasislescence . Under csomiasis , 6, 30. children . The exierienced , 78. FutSchistosoma infection can be reversed with treatment alone. The fact that infection often occurs in the context of malnutrition, coincident parasitic infections, and extreme poverty suggests that cognitive remediation efforts will need to be multi-faceted, using an integrated disease management framework. We expect that educational and cognitive interventions will be most effective if initiated earlier in life and that the package of interventions may need to include remedial instruction, the prevention of reinfection for treated/cured children, management of comorbid health conditions, and interventions for improvement of nutritional status.It is currently unknown whether the cognitive and educational loss associated with Schistosoma infection/non-treatment is associated with educational and cognitive loss. Our findings further suggest a definite cognitive and educational benefit of anti-schistosomal deworming among school-age children. Future complex intervention studies of early childhood interventions, focused on improving child well-being and cognitive potential, are needed to determine to what extent these observed deficits are preventable or reversible. Interventions that employ an integrated disease management framework will likely identify cost-efficiencies for leveraging existing disease and nutrition treatment programs in helminth-affected regions.Our investigation suggests that S1 Text(PDF)Click here for additional data file.S2 Text(DOCX)Click here for additional data file.S3 Text(DOCX)Click here for additional data file.S1 Table(DOCX)Click here for additional data file.S2 Table(DOCX)Click here for additional data file.S3 Table(DOCX)Click here for additional data file.S1 Fig(DOCX)Click here for additional data file.


The National Comprehensive Cancer Network™ (NCCN™) website has an evidence-based tool called the NCCN Imaging Appropriate Use Criteria (AUC) Compendium™ to help guide practitioners in choosing appropriate imaging for their patients. The NCCN Imaging AUC Compendium was developed in early 2016. The tool supports the most recent versions of the NCCN Guidelines™, with at least annual review.The NCCN Imaging AUC Compendium is a quick, easy-to-use tool to guide imaging decisions in the care plan of an individual with cancer, whether in screening, diagnosis, staging, treatment response assessment, or surveillance. The tool uses 44 diagnoses and references the NCCN Guidelines™ and page number where the information can be found. The design for decision-making on appropriate imaging, support, and timing in the NCCN Imaging AUC Compendium is developed by the multidisciplinary NCCN Guidelines panels, which include physicians, nurses, nurse practitioners, radiologists, and pharmacists . Like thhttp://www.nccn.org. From the main page, click on the NCCN Compendia tab at the top and then click on the fourth option down: NCCN Imaging AUC Compendium. Next, slide right to search the NCCN Imaging AUC Compendium. Before accessing this free tool, you will need to create an account by providing an e-mail address and accepting an End-User License Agreement.The NCCN Imaging AUC Compendium can be accessed on the NCCN website at The NCCN Imaging AUC Compendium tool consists of user-friendly, drop-down menus to guide the user specifically through categories associated with certain NCCN-supported guidelines. The tool may be customized by selecting the fields to display or hide. The drop-down menus allow the choice of a specific guideline, clinical setting (more specific diagnosis), purpose (such as diagnosis or staging), modality (type of test), and/or ICD-10 code.For example, the option of Breast Cancer within the NCCN Guideline drop-down menu will display only breast cancer–related diagnoses in the Clinical Setting drop-down menu vs. using the Prostate Cancer option and then having only the Prostate Cancer option under the Clinical Setting drop-down menu. The Clinical Setting allows a more specific choice, narrowing the image decision-making options.Under the Purpose drop-down menu, there are four options: Diagnostic/Staging, Treatment Response Assessment, Screening, and Follow-up/Surveillance . These oIn addition to the great benefits of the tool, ICD-10 codes are added for provider convenience. For added simplicity, there is an NCCN Imaging AUC Compendium User Guide on the page prior to accessing the tool.Advanced practitioners will find this tool useful in guiding decisions regarding scan choices. Data from this tool will provide needed evidence-based documentation to justify scans for payers.The NCCN Imaging AUC Compendium uses the data compiled by NCCN panel members in a convenient, easy-to-use tool to help guide practitioners order the imaging and surveillance deemed most appropriate and cost-effective. The imaging tool is a quick and informative reference tool. As knowledge increases and changes, so will the guidelines and tools. Additional cancers are being added quarterly; in 2016, 44 cancers were added, with 2 more scheduled to be added in 2017.PermissionNCCN referenced with permission from the NCCN Imaging Appropriate Use Criteria Compendium™ (NCCN Imaging AUC Compendium™) © National Comprehensive Cancer Network, Inc 2017. All rights reserved. To view the most recent and complete version of the NCCN Imaging AUC Compendium™, go online to NCCN.org. National Comprehensive Cancer Network®, NCCN®, NCCN Guidelines®, and NCCN Imaging AUC Compendium™, and all other NCCN Content are trademarks owned by the National Comprehensive Cancer Network, Inc.


Congenital complete atrioventricular block without any structural heart disease and anti-Ro/La negativity is very rare. Discordant complete atrioventricular block, which is more frequently defined in the literature as an autoimmune mechanism, is much more rare in monozygotic twins.The 26-year-old healthy mother had given birth in her first spontaneous, uneventful pregnancy to monozygotic twins at week 35. While the first twin’s physical examination proved her to be normal with a pulse rate consistent with her age, the second twin had a pulse rate of approximately 40 beats/minute.The patient was confirmed to have congenital complete atrioventricular block.Despite this case appears to be an isolated one, a discordant complete atrioventricular block regression without any autoimmune evidence should be included in the differential diagnosis of bradycardia in infants. Congenital complete atrioventricular block (CAVB) is seen in approximately one in every 20.000 live births. Congenital CAVB is rarer in patients that are anti-Ro/La negative or who do not exhibit any structural heart disease. More than 90% of congenital atrioventricular blocks (AVB) are accompanied by maternal autoimmune antibodies or structural heart disease. The remaining 10% are idiopathic AVB . We presThe 26-year-old healthy mother had given birth in her first spontaneous, uneventful pregnancy to monozygotic twins at week 35, one of whom had a birth weight of 2.320 grams. The mother did not have a history of infection, metabolic disease, autoimmune disease, or drug usage during the pregnancy period. After the evaluation of the fetuses at 35th week of gestation, an emergency cesarean section was performed on the diagnosis of fetal distress due to bradycardia of the index fetus which was determined by a non-stress test. Following birth, both babies had normal Apgar scores. While the first twin’s physical examination proved her to be normal with a pulse rate consistent with her age, the second twin had a pulse rate of approximately 40 beats/minute; therefore, the twin with bradycardia was hospitalized. Informed consent was obtained from the parents at this time. The patient was confirmed to have CAVB by 12-lead electrocardiography (ECG)  and 24-hour Holter monitorization  . No struThe immunological markers, including anti-Ro/SSA, anti-LA/SSB, anti-DNA, antinuclear antibody, anti-cardiolipin antibody, anti-Sm, U1-RNP, Jo-1 and Scl70, of both infants and the mother were found to be negative. Anti-Ro/SSA and anti-LA/SSB immunoblotting yielded negative results in a reference laboratory with ISO 15189 accreditation.At the first and sixth month follow-up visits, the auto-antibodies of the patient and the mother were checked for late seroconversion and were found to be negative. At the sixth month follow-up visit, both Holter monitoring and the ECG  indicateCongenital CAVB is rare in patients who are anti-Ro/La negative and have no concomitant structural heart diseases . BrucatoPrevious studies have reported that negative immune complex (anti-Ro or anti-La antibodies) findings do not always rule out an immune-mediated event; anti-Ro and anti-La antibodies can exhibit a stable profile for many years, but late seroconversion may remain a risk . MethodsDiscordant congenital CAVB is a rare occurrence in monozygotic twin infants . To the Furthermore, there are conflicting reports about the prognosis of congenital AVB patients. According to Berg et al. , the morOur conclusion is that discordant congenital CAVB may develop in monozygotic twins born to an autoimmune negative mother. The pathogenesis of this condition is still unknown. If the cardiac functions of such patients are normal, they may be clinically monitored until normal sinus rhythm is restored.


Adjacent segment pathology (ASP) is a common complication presenting in patients with axial pain and dysfunction, requiring treatment or follow-up surgery. However, whether minimally invasive surgery (MIS), including MIS transforaminal / posterior lumbar interbody fusion (MIS-TLIF/PLIF) decreases the incidence rate of ASP remains unknown. The aim of this meta-analysis was to compare the incidence rate of ASP in patients undergoing MIS versus open procedures.This systematic review was undertaken by following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement. We searched electronic databases, including PubMed, EMBASE, SinoMed, and the Cochrane Library, without language restrictions, to identify clinical trials comparing MIS to open procedures. The results retrieved were last updated on June 15, 2016.Overall, 9 trials comprising 770 patients were included in the study; the quality of the studies included 4 moderate and 5 low-quality studies. The pooled data analysis demonstrated low heterogeneity between the trials and a significantly lower ASP incidence rate in patients who underwent MIS procedure, compared with those who underwent open procedure (p = 0.0001). Single-level lumbar interbody fusion was performed in 6 trials of 408 patients and we found a lower ASP incidence rate in MIS group, compared with those who underwent open surgery (p = 0.002). Moreover, the pooled data analysis showed a significant reduction in the incidence rate of adjacent segment disease (ASDis) (p = 0.0003) and adjacent segment degeneration (ASDeg) (p = 0.0002) for both procedures, favoring MIS procedure. Subgroup analyses showed no difference in follow-up durations between the procedures (p = 0.93).Therefore, we conclude that MIS-TLIF/PLIF can reduce the incidence rate of ASDis and ASDeg, compared with open surgery. Although the subgroup analysis did not indicate a difference in follow-up duration between the two procedures, larger-scale, well-designed clinical trials with extensive follow-up are needed to confirm and update the findings of this analysis. The prevalence of adjacent segment pathology (ASP) requiring additional treatment after spinal fusion surgery has recently become more concerning –3. AdjacAlthough the pathophysiology of these conditions remains uncertain, they have shown to perform a significant impact on modern society, not only physically through increased patient morbidity, but also financially due to loss of productivity and increased healthcare costs , 19. WhiHence, whether MIS can decrease the incidence rate of ASDeg and ASDis in patients with degenerative disc disease or spondylolisthesis is unknown. To our knowledge, no meta-analysis has been published on this topic to date. Thus, it is timely to critically review the trials in this field and compare the incidence rate of ASDeg and ASDis among patients in MIS and open procedures.We strictly followed the Cochrane Handbook for Systematic Reviews of Interventions protocol . The stuWe searched PubMed, EMBASE, SinoMed, and the Cochrane Library databases on June 15, 2016, without restricting the region, publication type, or language. The Mesh terms and Text words were all searched. The related articles function was also used to broaden the search, and the computer search was supplemented with manual searches of the reference lists of all retrieved studies and review articles. The following search strategy was used: (((((ASD) OR ASDis) OR ASDeg) OR ASP) OR adjacent segment disease) OR adjacent segment degeneration) and  OR MIS) OR pertacuneous). The detailed search strategy were uploaded in supply materials and flow diagram are shown in Two reviewers independently extracted relevant information from each eligible study. Information about the characteristics of the study participants, details of the interventions used, comparisons, and relevant outcomes were recorded. Clinical studies with a randomized controlled trial (RCT) or non-randomized controlled trial (non-RCTs) design in any phase were included. Exclusion criteria included comparative single-arm or no-control trials, case series, case reports, review articles, editorials, letters, surveys, economic studies, and unrelated publications. The outcomes were cross-checked independently, and any inconsistencies in the results were discussed. The exhaustive search is detailed in The methodological quality of each study included in the meta-analysis was evaluated using the Cochrane Handbook for Systematic Reviews of Interventions (version 5.2.0). RCTs were evaluated using the Cochrane Collaboration tool to assess the risk for bias, and non-RCTs were assessed using the modified Newcastle-Ottawa scale , which c2>50% or P<0.10 indicated heterogeneity between different trials. To demonstrate more robust results, a random-effects model was applied to data analyses.All meta-analyses were performed using Review Manager 5.2.0 ; publication bias was checked using Stata 11.0.  via the Beg and Egger test . The weiThe PubMed, EMBASE, SinoMed, and Cochrane Library databases search  yielded The basic characteristics and the matching information of patients clinical characteristics on the 9 trials included in the meta-analysis is respectively summarized in Tables Although the high methodological quality of the evidence was assessed using the modified Newcastle-Ottawa scale , all 9 sThe quality of the evidence for each study was evaluated and is shown in 2 = 0%) between the 9 trials (N = 770) evaluating the incidence rate of ASP in no less than 6 months; a significantly lower incidence of ASP was seen in the MIS group, compared with the open group . The short-term follow-up incidence rate (≤2 years) reported by 2 studies (n = 197) showed a decreasing trend in the MIS group; the difference was not significant  and mid-term subgroups (P = 0.32), a significantly lower incidence rate of ASP was observed in the long-term subgroup (P = 0.001). These differences may be due to the small sample size in the short- and mid-term studies. It should be noted that the pathological process of ASDeg and ASDis are considered long-term complications following spinal fusion surgery. Altogether, the trends observed in these subgroup analyses (p = 0.93) may suggest that MIS procedure decreases the incidence rate of ASP in all 3 different follow-up durations.For further understanding the similar protection or reduction incidence methods of ASP, we also searched for systematic reviews and meta-analyses comparing different interventions of ASP incidence . The artNonetheless, MIS surgery as a new kind of technology requires a additionally steep learning curve. Besides, this method is associated with significantly longer X-ray exposure dose and need complete protection such as wearing leaded apron and glasses during surgery. Both of this may increase the excess cost. At last, it is a technical challenging of MIS procedure due to smaller operative field that may hinder the accurate decompression, interbody fusion and pedicle screw placement.We acknowledge that this meta-analysis also had some limitations. First, all 9 studies included were non-RCTs—no RCT were included—which could significantly affect the quality of our meta-analysis. However, conducting RCTs is difficult, because of patient expectations and complex procedures, highlighting the importance of this meta-analysis. Second, small number of studies/patients just including the comparative studies written by MIS-surgeons in this study may weaken our conclusion in certain extent. Consequently, it was difficult to perform a sensitivity analysis with only 9 studies. Third, the inclusion criteria for MIS and open procedures may be different. For example, patients with severe lumbar instability and spondylolysis may have been more likely to be assigned to the open surgery group, which could have affected our results. Lastly, some between-study heterogeneity may be attributable to socioeconomic factors, nutrition, and matching criteria. These differences could have been reduced using a random-effects model, but they would have been difficult to remove all together.Based on this meta-analysis, we conclude that patients undergoing MIS procedure may have a lower incidence of ASDeg and ASDis, than those undergoing open surgery. The subgroup analysis evaluating follow-up duration showed no difference between the procedures. Nonetheless, large-volume, well-designed clinical trials with extensive follow-up, are still needed to confirm and update the findings of this analysis.S1 File(DOC)Click here for additional data file.


Spatial group independent component analysis (GICA) methods decompose multiple-subject functional magnetic resonance imaging (fMRI) data into a linear mixture of spatially independent components (ICs), some of which are subsequently characterized as brain functional networks. Group information guided independent component analysis (GIG-ICA) as a variant of GICA has been proposed to improve the accuracy of the subject-specific ICs estimation by optimizing their independence. Independent vector analysis (IVA) is another method which optimizes the independence among each subject's components and the dependence among corresponding components of different subjects. Both methods are promising in neuroimaging study and showed a better performance than the traditional GICA. However, the difference between IVA and GIG-ICA has not been well studied. A detailed comparison between them is demanded to provide guidance for functional network analyses. In this work, we employed multiple simulations to evaluate the performances of the two approaches in estimating subject-specific components and time courses under conditions of different data quality and quantity, varied number of sources generated and inaccurate number of components used in computation, as well as the presence of spatially subject-unique sources. We also compared the two methods using healthy subjects' test-retest resting-state fMRI data in terms of spatial functional networks and functional network connectivity (FNC). Results from simulations support that GIG-ICA showed better recovery accuracy of both components and time courses than IVA for those subject-common sources, and IVA outperformed GIG-ICA in component and time course estimation for the subject-unique sources. Results from real fMRI data suggest that GIG-ICA resulted in more reliable spatial functional networks and yielded higher and more robust modularity property of FNC, compared to IVA. Taken together, GIG-ICA is appropriate for estimating networks which are consistent across subjects, while IVA is able to estimate networks with great inter-subject variability or subject-unique property. There is a rapidly increasing interest in using functional magnetic resonance imaging (fMRI) data to characterize brain functional networks. Independent component analysis (ICA), a data-driven method, has been widely used to analyze fMRI data without requiring the definition of brain regions (or nodes). Spatial ICA (sICA) , an alternative method to achieve an independent decomposition . There are mainly two steps: (1) performing subject-level PCA on each subject's data; (2) applying IVA-GL to estimate the subject-specific components and time courses (TCs). The estimated components are then Z-scored. A free parameter is the number of components used for the subject-level PCAs, denoted as I1.As for IVA, IVA-GL algorithm was adopted to estimate components for comparisons in this work. It can be accessed in Group ICA for fMRI toolbox (GIFT)  of GIG-ICA and IVA-GL algorithm are comparable, since both methods use fixed nonlinearity matched to super-Gaussian sources.It is worth noting that in order to decrease computation load, GIG-ICA can remove artifact-related group-level ICs before estimating individual components  and their corresponding TCs (150 or less time points in length) were simulated and then used to generate data by a linear mixture model. In our experiments, we set C to be 7 or 8. Rician noise was then added to data with a specified contrast-to-noise ratio (CNR). Repetition time (TR) was 2 s/sample. Among C sources, some sources were similar across all subjects with slight variance , while the other sources were unique and only present on specific subject . These subject-unique sources were generated to simulate significant source variability across subjects. The parameters of our experiments are summarized in Table Due to that there is no ground truth in practical applications, simulation-based tests are necessary for evaluating different methods. In order to comprehensively compare IVA and GIG-ICA, we performed several experiments to assess the accuracy of the estimated individual components and TCs under different conditions, including various data quality and quantity (Experiment 1), varied number of sources and inaccurate number of components for computation (Experiment 2), and spatially subject-unique sources (Experiment 3). In each experiment, we simulated fMRI-like data of multiple subjects using the SimTB toolbox , and spatial extents  of the common spatial map . Thereby, sources were spatially consistent across subjects but showing moderate subject-specific variability, as shown in Figure G1, G2, I1) used in the analyses to be the same as the number of true sources .As shown in Figure In this section, we first assessed the performance of the two methods using data with varied number of sources across different subjects  accuracy metrics of all subjects from IVA with that from GIG-ICA. In Experiment 3, for each component, we compared the spatial  accuracy of all subjects between IVA and GIG-ICA using one two-tailed paired t-test. The results were corrected using p < 0.05 with Bonferroni correction.To compare the performance of IVA and GIG-ICA on simulations, we evaluated accuracy of the estimated subject-specific components and TCs using correlation between estimation and ground truth, consistent to many prior studies . The first scan (scan 1) is in a scan session. Five to Sixteen months (mean 11 ± 4) after scan 1, scan 2 and scan 3 were conducted with short interval (about 45 min). The fMRI images were preprocessed using SPM8 (http://www.fil.ion.ucl.ac.uk/spm). The first 10 images were discarded, and the remaining 187 images were slice-time corrected and realigned to the first volume for head-motion correction. Subsequently, the images were spatially normalized to the Montreal Neurological Institute (MNI) EPI template and spatially smoothed with a 6 mm FWHM Gaussian kernel.Seventy five resting-state fMRI datasets  correction) were performed on the corresponding networks of all 75 datasets. Next, since the data from scan 2 and scan 3 were collected with short intervals, voxel-wise intra class coefficients (ICCs)  as well as reliability in both connectivity and modularity. First, for each dataset, we obtained one FNC matrix by computing Pearson correlation coefficients between the associated TCs of any paired networks. Next, we averaged the FNC matrix across all 75 datasets. Based on the mean FNC matrix, we detected its modules  using the most applied eigenvector-based method , consistent to a recent study . Our results suggest that for the data generated with subject-unique sources, in general GIG-ICA still performed well for the similar sources but did not work well for the unique source. In contrast, IVA can estimate the subject-unique source and its associated TC with high accuracy.In this experiment, we tested the two methods using datasets where each subject had a spatially unique source. Accuracy of each estimated individual component/TC is shown in Figure t-tests results of the 12 matched networks for the two methods under the condition of the model order as 30. We found that compared to IVA, GIG-ICA in general showed higher t-values for all networks. For the case of the model order as 30, the short-term and long-term reliability measures of each network are demonstrated in Figures Using the test-retest resting-state fMRI datasets, we assessed the individual-level spatial networks in terms of their short-term and long-term reliability. Figure Q = 1.33) compared to IVA (Q = 0.51) when the number of components was 100.We also compared the two methods in constructing functional interaction among networks. Under a model order of 100, 22 networks were highly matched between the two methods. For each dataset, one FNC matrix was generated based on the associated TCs of the 22 networks. Figures Q-value of the mean FNC than IVA for the model order settings tested  for analyzing multi-subject fMRI data. Both methods can estimate subject-specific brain functional networks with correspondence across different subjects. IVA considers both the independence of individual components and the dependence of similar components across subjects. GIG-ICA first estimates the group-level ICs from all data and then computes the subject-specific ICs with the group-level ICs as guidance. Using simulations, we investigated if the two methods can yield accurate individual-level components and time courses under different conditions, including different data quality  and data quantity , varied number of sources and inaccurate number of components, as well as presence of spatially subject-unique sources. Furthermore, we assessed their performance using test-retest resting-state fMRI data with respect to spatial networks' reliability and graph-theory based metrics of FNC under different model orders.In Experiment 1 using simulations, we evaluated the two methods using data with various quality and quantity. Our results suggest that both IVA and GIG-ICA showed improved performance along with the increased CNR and time points of data. For the sources with slight inter-subject spatial variability, GIG-ICA obtained components with higher accuracy than IVA, and performed very well under the case of low CNR and less time points. It is known that both IVA and GIG-ICA require a fixed number of components for computation, generating the same number of components for all subjects. When datasets of different subjects are simulated using different numbers of sources, the resulting components of some subjects have different numbers with the real number of sources. So, in Experiment 2, we simulated varied number of sources between different groups and also investigated the influence of inaccurate number of components. Our results suggest that GIG-ICA showed a relatively better performance and was stable to the various numbers of sources under this case. We also tested the two methods in terms of the effect of the number of components, indicating that IVA gave rise to a significant reduced accuracy when the model order was underestimated while GIG-ICA was not very sensitive to the inaccurate model order.All the above mentioned experiments were applied to the datasets generated using sources that were similar across subjects. In Experiment 3, using datasets where all subjects had a subject-unique source with large inter-subject spatial variability, we found that IVA significantly showed a better performance in the component/TC accuracy of the unique source than GIG-ICA, although GIG-ICA in general still performed better for other subject-common sources compared to IVA. This is likely due to that the two methods are different in algorithm level. GIG-ICA first extracts the group-level components, and then estimates the corresponding individual-level components for each individual-subject's data. In contrast, IVA simultaneously estimates the individual-subject's components and optimizes the dependence of components across different subjects. Therefore, we suggest using GIG-ICA to estimate networks that are consistent across subjects, while IVA is more appropriate for networks with significant inter-subject variability. IVA's superiority in estimating subject-unique sources possibly enables it to be more suitable to data from patients with particular brain structure damage, such as patients suffering from brain tumor that could result in greatly different functional networks. Our previous work  using GIG-ICA compared to IVA for most of the model order settings examined. Measured by the AMI, the modular structure was more reliable during short-term and long-term rescanning using GIG-ICA for all tests, compared to using IVA. Despite short-term and long-term, ICC measures demonstrate that connectivity strengths were generally more robust using GIG-ICA method, compared to IVA. Moreover, FNC obtained from GIG-ICA showed relatively higher values in the averaged node strength, clustering coefficient, global efficiency, and local efficiency, indicating stronger interaction among brain functional networks.Our experiments using healthy participants' test-retest resting-state fMRI data revealed that regardless of low model order and high model order, GIG-ICA in general obtained functional networks with relatively greater short-term and long-term reliability compared to IVA, although a few networks showed slightly higher reliability in IVA than GIG-ICA. In terms of the interaction among networks represented by FNC, we found that the mean FNC matrix from the two methods showed a similar pattern to some extent. However, both the mean FNC and the individual-level FNC showed stronger modularity  The simulations are quite simple. Only eight sources and ten subjects were simulated, while the proportion in fMRI data is certainly greater. In practical applications, there exist more complex situations that could involve many subject-unique sources, high diversity in source number, and great bias in model order estimation. Therefore, it's possible that conclusions we draw from simulations are over-simplified and of limited applicability. However, we also evaluated the two methods using data with more subject-common and subject-unique sources. The results are included in the Supplementary Materials Figures , S4. Ourhttp://www.nitrc.org/projects/nyu_trt. Data were collected according to protocols approved by the institutional review boards of New York University (NYU) and the NYU School of Medicine. The related information can be found in Zuo et al. (The fMRI data we used are open. These data are fully available via o et al. . ReliablYD designed the study; analyzed and interpreted the data; revised the manuscript; and gave final approval. DL interpreted the results; drafted the manuscript and gave final approval. QY interpreted the results; revised the manuscript and gave final approval. JS interpreted the data; revised the manuscript and gave final approval. JC interpreted the results; revised the manuscript and gave final approval. SR helped with IVA implementation, interpreted the data; drafted and revised the manuscript; gave final approval. TA interpreted the data; drafted and revised the manuscript; gave final approval. VC designed the study; interpreted the data; drafted and revised the manuscript; gave final approval.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Remarkable advances in Next Generation Sequencing (NGS) technologies, bioinformatics algorithms and computational technologies have significantly accelerated genomic research. However, complicated NGS data analysis still remains as a major bottleneck. RNA-seq, as one of the major area in the NGS field, also confronts great challenges in data analysis.de novo assembly and uses RSEM for transcript quantification and EdgeR for differential analysis. The third combines STAR, RSEM, and EdgeR for data analysis. All these workflows support multiple samples and multiple groups of samples and perform differential analysis between groups in a single workflow job submission. The calculated results are available for download and post-analysis. The supported animal species include chicken, cow, duck, goat, pig, horse, rabbit, sheep, turkey, as well as several other model organisms including yeast, C. elegans, Drosophila, and human, with genomic sequences and annotations obtained from ENSEMBL.To address the challenges in RNA-seq data analysis, we developed a web portal that offers three integrated workflows that can perform end-to-end compute and analysis, including sequence quality control, read-mapping, transcriptome assembly, reconstruction and quantification, and differential analysis. The first workflow utilizes Tuxedo . The second workflow deploys Trinity for http://weizhongli-lab.org/RNA-seq.The RNA-seq portal is freely available from The web portal offers not only bioinformatics software, workflows, computation and reference data, but also an integrated environment for complex RNA-seq data analysis for agricultural animal species. In this project, our aim is not to develop new RNA-seq tools, but to build web workflows for using popular existing RNA-seq methods and make these tools more accessible to the communities. Remarkable advances in Next Generation Sequencing (NGS) technologies  and compSequencing steady-state RNA in a biological sample (RNA-seq) , 3, as oIn the past years, many tools and methods have been developed for RNA-seq data analysis. Some major categories of these tools including read-mapping, transcriptome assembly or reconstruction, and expression quantification .Aligning RNA-seq reads against a reference genome or transcriptome (a.k.a read-mapping) is the most common job when a reference is available. There are a large number of general purpose aligners available such as Bowtie , 6, BWA de novo assemblers that don’t require reference genomes.Transcriptome reconstruction or RNA-seq assembly is another route to analyze RNA-seq data. This can be performed with or without a reference genome. Scripture  and CuffMapping and assembly are relatively computation-intensive jobs, which supply data for downstream expression quantification using programs such as Cufflinks , MISO 2 and RSEMTo make sense of RNA-seq data, a full analysis pipeline usually requires multiple procedures and different tools. Besides the RNA-seq specific tools discussed above, many other NGS data processing tools are also required such as SolexQA  and TrimDifficulties in creating these complicated computational pipelines, installing and maintaining software packages, and obtaining sufficient computational resources all tend to overwhelm bench biologists from attempting to analyze their own RNA-seq data. So, despite the availability of the great set of computational tools and methods for RNA-seq data analysis, it is still very challenging for a biologist to deploy these tools, integrate them into workable pipelines, find accessible computational platforms, configure the compute environment, and perform the actual analysis.Today, RNA-seq has been widely used in animal studies, so developing integrated bioinformatics systems specific to agricultural species, especially easy-to-use web portals, is of great importance for researchers in the agricultural community.de novo assembly, RSEM [http://weizhongli-lab.org/RNA-seq for all users. The backend software package is also available as open source software.To this end, we have developed a web portal offering integrated workflows that can perform end-to-end compute and analysis, including sequence  QC, read-mapping, transcriptome assembly, reconstruction and quantification, and multiple analysis tools. The first workflow utilizes the Tuxedo suite of tools   for comply, RSEM  for tranly, RSEM  for diffly, RSEM , RSEM anhttp://star.mit.edu/cluster/docs/latest/index.html), running on modern scalable cloud compute and storage sources from Amazon Web Services (AWS).The portal is implemented with several state-of-the-art High Performance Computing (HPC), workflow and web development software tools including Galaxy , StarCluThe system is illustrated in Fig. Once the head node is up and running, the virtual cluster can be controlled within this head node, where StarCluster software is also installed. The virtual cluster is configured with Open Grid Engine (OGE) job scheduling system with parallel environment enabled. All user-submitted jobs will be managed by the OGE. The StarCluster auto-scaling script, which runs in the background on the head node, automatically starts up new compute nodes when jobs are waiting in the OGE queue and shuts them down when the queue empties, reducing compute costs.An Apache web server runs on the head node. It supports the RNA-seq portal website and provides reference genome data and user data download. An FTP server also runs on the head node, allowing users to download reference genome data and upload user data. A MySQL server is used in tracking user jobs and supporting the Galaxy server. The RNA-seq portal documentation is supported by a DokuWiki server.Galaxy  is a webRNA-seq data analysis requires workflows with multiple procedures and many different tools. The tools all have different requirement in computer memory, I/O speed, disk space, network bandwidth, density of computing cores, parallel environment settings etc. So given a computer grid or cloud infrastructure, it is not trivial to make a fully automated workflow that meets the requirements of all distinct tools and maximize the usage of provided compute resources.The Galaxy platform supports running individual compute tools and also supports workflow integration. However, the workflow function offered by Galaxy requires users to have relatively deep knowledge of Galaxy software and the tools being integrated into the workflows, so it is quite difficult for common users to fully take advantage of the Galaxy workflow capacity.In this project, we provided users with pre-configured workflows, which are launched as standalone tools from the Galaxy interface. The workflows in this project are configured with a lightweight workflow engine we developed in our earlier projects , supportThe RNA-seq portal offers three integrated workflows. All these workflows are implemented so that a user can run multiple groups of samples under different conditions  with a single job submission. A workflow will perform identical process (e.g. read-mapping) for each individual sample, then compare results between groups, and can also analyze data based on pooled samples or groups.The Tophat, Cufflink, Cuffmerge and Cuffdiff workflow, also know as the Tuxedo Package , is one Given user input sequence files in FASTQ format for several groups of samples, the workflow first runs a three step sub-workflow for each individual: (1) Sequence QC: for either Paired End (PE) or Single End (SE) read input, remove low quality reads and trim low quality bases using Trimmomatic  with defThe results of this process are then combined into a single merged transcriptome annotation with Cuffmerge. Finally, for each pair of sample groups, Cuffdiff is used to identify differentially expressed genes and transcripts between them.http://trinityrnaseq.github.io. The structure is outlined in Fig. This workflow is implemented according to the Trinity protocol . AdditioThis workflow first uses Trinity to assemble all samples together into a combined transcriptome. It then indexes the transcriptome sequences using bowtie and annotates transcripts by comparing them to cDNA sequences from reference genomes using BLASTN . TrinityThis workflow uses STAR , an ultrTuxedo and STAR workflows are reference genome/transcriptome based approaches. When reference genomes are available and the main goal is to quantify the expression level of known genes and transcripts, then these two workflows are the choice. Tophat2 and STAR are both very popular aligners. Regarding the accuracy and performance, they have been extensively evaluated, compared and discussed along with many other aligners in algorithm papers and in reviews , 38, 39,When there is no reference genome available or the reference genome is poorly assembled or annotated, Trinity workflow can be utilized in RNA-seq analysis. This is important for many non-model organisms or cancer samples.Given the convenience of our web portal job submission, it is possible for users to run multiple workflows on the same dataset once the input data are uploaded to users’ workplace. That way, it is possible to compare the results to see whether consistent observations can be obtained with different approaches, to identify questionable results, and to look for method specific predictions.The web portal to run the workflows  into an instance of the Integrative Genomics Viewer (IGV)  by proviC. elegans, Drosophila, and others .http://weizhongli-lab.org/RNA-seq.To support users who prefer to run these workflows locally or want to setup web portal on their own servers, with the flexibility of using different parameters, our backend software package is available as open source software. The software package needs to be installed on generic Linux computer clusters that support Open Grid Engine. These systems are widely available from HPC facilities in Universities and institutions, as well as from Cloud providers (e.g. Amazon Web Services). The installation documents are available from our project page at Project name: RNA-seq web portal for animal specieshttp://weizhongli-lab.org/RNA-seq.Project home page: Operating system(s): Platform independentProgramming language: Perl (client-side scripts)Other requirements: web browsersLicense: no license neededAny restrictions to use by non-academics: no restriction