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Cancers Jul 2020Colorectal cancer (CRC) is one of the most common cancers requiring early pathologic diagnosis using colonoscopy biopsy samples. Recently, artificial intelligence (AI)...
Colorectal cancer (CRC) is one of the most common cancers requiring early pathologic diagnosis using colonoscopy biopsy samples. Recently, artificial intelligence (AI) has made significant progress and shown promising results in the field of medicine despite several limitations. We performed a systematic review of AI use in CRC pathology image analysis to visualize the state-of-the-art. Studies published between January 2000 and January 2020 were searched in major online databases including MEDLINE (PubMed, Cochrane Library, and EMBASE). Query terms included "colorectal neoplasm," "histology," and "artificial intelligence." Of 9000 identified studies, only 30 studies consisting of 40 models were selected for review. The algorithm features of the models were gland segmentation ( = 25, 62%), tumor classification ( = 8, 20%), tumor microenvironment characterization ( = 4, 10%), and prognosis prediction ( = 3, 8%). Only 20 gland segmentation models met the criteria for quantitative analysis, and the model proposed by Ding et al. (2019) performed the best. Studies with other features were in the elementary stage, although most showed impressive results. Overall, the state-of-the-art is promising for CRC pathological analysis. However, datasets in most studies had relatively limited scale and quality for clinical application of this technique. Future studies with larger datasets and high-quality annotations are required for routine practice-level validation.
PubMed: 32668721
DOI: 10.3390/cancers12071884 -
BMC Complementary Medicine and Therapies Jun 2020African Potato (hypoxis hemerocallidea), is used for enhancing immune system in Southern Africa. It is among the plants of intense commercial and scientific interest;...
BACKGROUND
African Potato (hypoxis hemerocallidea), is used for enhancing immune system in Southern Africa. It is among the plants of intense commercial and scientific interest; hence, the aim of this study was to describe its chemistry and pharmacology.
METHODS
PubMed, Cochrane Controlled Trials Register (CENTRAL) and Google Scholar were searched independently for relevant literature. The last search occurred in October 2018. Other research material was obtained from Google. The following search terms were used, but not limited to: "African Potato", "hypoxis", "hemerocallidea", "rooperol." Articles that were explaining the chemistry and pharmacology of hypoxis hemerocallidea were included.
RESULTS
Thirty articles from PubMed, Cochrane and Google Scholar were eligible. Three webpages were included from Google. Results showed that the tuberous rootstock (corm) of African Potato is used traditionally to treat wasting diseases, testicular tumours, insanity, barrenness, impotency, bad dreams, intestinal parasites, urinary infection, cardiac disease and enhancing immunity. The plant contains hypoxoside, which is converted rapidly to a potent antioxidant, rooperol in the gut. The corm contains sterols, sterol glycosides, stanols, terpenoids, saponins, cardiac glycosides, tannins and reducing sugars. A dose of 15 mg/kg/day of hypoxoside is reportedly therapeutic. Preclinical studies of African Potato have shown immunomodulation, antioxidant, antinociceptive, hypoglycaemic, anti-inflammatory, anticonvulsant, antibacterial, uterolytic, antimotility, spasmolytic and anticholinergic effects. The common side effects of African Potato are nausea and vomiting, which subside over time. In vitro, African Potato demonstrated inhibitory effects on CYP1A2, 2C9, 2D6, 3A4, 3A5, CYP19-metabolism and induction of P-glycoprotein. In vivo, it did not alter the pharmacokinetics of efavirenz or lopinavir/ritonavir.
CONCLUSION
African Potato is mainly used as an immunostimulant. The exact mechanisms of action for all the pharmacological actions are unknown. More research is required to substantiate claims regarding beneficial effects. There are many research gaps that require investigation including pharmacokinetic interactions with conventional drugs, especially those used in HIV/AIDS.
Topics: Africa; Catechols; Humans; Hypoxis; Medicine, African Traditional; Plant Extracts; Plants, Medicinal
PubMed: 32527245
DOI: 10.1186/s12906-020-02956-x -
Respiratory Research Apr 2020Subphenotypes were recently reported within clinical acute respiratory distress syndrome (ARDS), with distinct outcomes and therapeutic responses. Experimental models... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Subphenotypes were recently reported within clinical acute respiratory distress syndrome (ARDS), with distinct outcomes and therapeutic responses. Experimental models have long been used to mimic features of ARDS pathophysiology, but the presence of distinct subphenotypes among preclinical ARDS remains unknown. This review will investigate whether: 1) subphenotypes can be identified among preclinical ARDS models; 2) such subphenotypes can identify some responsive traits.
METHODS
We will include comparative preclinical (in vivo and ex vivo) ARDS studies published between 2009 and 2019 in which pre-specified therapies were assessed (interleukin (IL)-10, IL-2, stem cells, beta-agonists, corticosteroids, fibroblast growth factors, modulators of the receptor for advanced glycation end-products pathway, anticoagulants, and halogenated agents) and outcomes compared to a control condition. The primary outcome will be a composite of the four key features of preclinical ARDS as per the American Thoracic Society consensus conference (histologic evidence of lung injury, altered alveolar-capillary barrier, lung inflammatory response, and physiological dysfunction). Secondary outcomes will include the single components of the primary composite outcome, net alveolar fluid clearance, and death. MEDLINE, Embase, and Cochrane databases will be searched electronically and data from eligible studies will be extracted, pooled, and analyzed using random-effects models. Individual study reporting will be assessed according to the Animal Research: Reporting of In Vivo Experiments guidelines. Meta-regressions will be performed to identify subphenotypes prior to comparing outcomes across subphenotypes and treatment effects.
DISCUSSION
This study will inform on the presence and underlying pathophysiological features of subphenotypes among preclinical models of ARDS and should help to determine whether sufficient evidence exists to perform preclinical trials of subphenotype-targeted therapies, prior to potential clinical translation.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO (ID: CRD42019157236).
Topics: Adrenergic beta-Agonists; Animals; Disease Models, Animal; Humans; Phenotype; Positive-Pressure Respiration; Randomized Controlled Trials as Topic; Respiratory Distress Syndrome; Treatment Outcome
PubMed: 32264897
DOI: 10.1186/s12931-020-01337-9 -
Sleep Medicine Mar 2020Nightmares are a highly prevalent and distressing feature of post-traumatic stress disorder (PTSD). Previous studies have reached mixed conclusions regarding the effects... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Nightmares are a highly prevalent and distressing feature of post-traumatic stress disorder (PTSD). Previous studies have reached mixed conclusions regarding the effects of prazosin on nightmares, sleep quality, and overall PTSD symptoms in patients with PTSD.
METHODS
MEDLINE, EMBASE, all EBM databases, PsycIFNO, and CINAHL were systematically searched from inception date to October 2018 for randomized clinical trials that included reporting of nightmares, sleep quality or overall PTSD symptoms. The analysis included data from eight trials involving 286 PTSD patients in the prazosin group and 289 PTSD patients in the placebo group.
RESULTS
In our meta-analysis, prazosin resulted in a statistically significant improvement in nightmares (standardized mean difference (SMD) = -1.13, 95% confidence interval (CI) = -1.91 to -0.36), but was not more beneficial than placebo for overall PTSD symptoms (SMD = -0.45, 95% CI = -0.95 to 0.05) and sleep quality (SMD = -0.44, 95% CI = -1.44 to 0.55). In terms of acceptability, there was no significant difference between the prazosin group and the placebo group with respect to discontinuation for all causes (odds ratio (OR) = 1.00, 95% CI = 0.62-1.62). In conclusion, the use of prazosin was associated with an improvement of nightmare symptoms.
CONCLUSION
Our findings indicate that additional studies are needed before considering downgrading the use of prazosin in the treatment of nightmares in patients with PTSD.
Topics: Antihypertensive Agents; Dreams; Humans; Prazosin; Randomized Controlled Trials as Topic; Sleep Wake Disorders; Stress Disorders, Post-Traumatic
PubMed: 31972510
DOI: 10.1016/j.sleep.2019.06.010 -
PloS One 2019Child maltreatment can have serious effects on development and physical, social and emotional wellbeing. Any long-lasting relational effects can impede the capacity to... (Meta-Analysis)
Meta-Analysis
Healing The Past By Nurturing The Future: A qualitative systematic review and meta-synthesis of pregnancy, birth and early postpartum experiences and views of parents with a history of childhood maltreatment.
BACKGROUND
Child maltreatment can have serious effects on development and physical, social and emotional wellbeing. Any long-lasting relational effects can impede the capacity to nurture children, potentially leading to 'intergenerational trauma'. Conversely, the transition to parenthood during pregnancy, birth and the early postpartum period offers a unique life-course opportunity for healing. This systematic review aims to understand the pregnancy, birth and early postpartum experiences of parents who reported maltreatment in their own childhood.
METHODS
A protocol, based on the ENTREQ statement, was registered with PROSPERO. We searched Medline, PsycINFO, CINAHL, EMBASE, NHS Evidence and key Web of Science databases from date of inception to June 2018 to identify qualitative studies exploring perinatal experiences of parents who were maltreated in their own childhood. Two reviewers independently screened articles for inclusion and extracted data. Data were synthesised using grounded theory and thematic analysis approaches.
FINDINGS
The search yielded 18329 articles, 568 full text articles were reviewed, and 50 studies (60 articles) met inclusion criteria for this review. Due to the large number of studies across the whole perinatal period (pregnancy to two years postpartum), this paper reports findings for experiences during pregnancy, birth and early postpartum (27 studies). Parents described positive experiences and strategies to help them achieve their hopes and dreams of providing safe, loving and nurturing care for their children. However, many parents experienced serious challenges. Seven core analytic themes encapsulated these diverse and dynamic experiences: New beginnings; Changing roles and identities; Feeling connected; Compassionate care; Empowerment; Creating safety; and Reweaving a future.
CONCLUSIONS
Pregnancy birth and the early postpartum period is a unique life-course healing opportunity for parents with a history of maltreatment. Understanding parent's experiences and views of perinatal care and early parenting is critical for informing the development of acceptable and effective support strategies.
Topics: Adult Survivors of Child Abuse; Female; Humans; Parenting; Parents; Parturition; Postpartum Period; Pregnancy; Pregnant Women
PubMed: 31834894
DOI: 10.1371/journal.pone.0225441 -
The British Journal of Radiology Feb 2020The recent increase in publications on radiomic analysis as means to produce diagnostic and predictive biomarkers in head and neck cancers (HNCC) reveal complicated and...
Radiomic analysis for response assessment in advanced head and neck cancers, a distant dream or an inevitable reality? A systematic review of the current level of evidence.
OBJECTIVE
The recent increase in publications on radiomic analysis as means to produce diagnostic and predictive biomarkers in head and neck cancers (HNCC) reveal complicated and often conflicting results. The objective of this paper is to systematically review the published data, and evaluate the current level of evidence accumulated that would determine clinical application.
METHODS
Articles in the English language available on the Ovid-MEDLINE and Embase databases were used for the literature search. :Studies which evaluated the role of radiomics as a predictive or prognostic tool for response assessment in HNCC were included in this review.Study appraisal and synthesis methods: The authors set-out to perform a meta-analysis, however given the small number of studies retrieved that presented adequate data, combined with excessive methodological heterogeneity, we could only perform a structured descriptive systematic review summarizing the key findings. Independent extraction of articles was performed by two authors using predefined data fields and any disagreement was resolved by consensus.
RESULTS
Though most papers concluded that radiomics is an effective predictive and prognostic biomarker in the management of HNCC, significant heterogeneity exists in the study methodology and statistical modelling; thus precluding accurate mathematical comparison or the ability to make clear recommendations going forwards. Moreover, most studies have not been validated and the reproducibility of their results will be a challenge.
CONCLUSION
Until robust external validation studies on the reproducibility and accuracy of radiomic analysis methods on HNCC are carried out, the current level of evidence remains low, with the authors advising caution against hasty implementation of these tools in the multidisciplinary clinic.
ADVANCES IN KNOWLEDGE
This review is the first attempt to critically analyze the merits and demerits of currently published literature on tumour heterogeneity studies in HNCC, and identifies specific loop holes that need to be addressed by research groups, for a meaningful clinical translation of this potential biomarker.
Topics: Head and Neck Neoplasms; Humans; Magnetic Resonance Imaging; Positron Emission Tomography Computed Tomography; Prognosis; Tomography, X-Ray Computed
PubMed: 31682155
DOI: 10.1259/bjr.20190496 -
The Lancet. Global Health Nov 2019The roll-out of antiretroviral therapy (ART) has changed contexts of HIV risk, but the influence on HIV incidence among young women is not clear. We aimed to summarise... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The roll-out of antiretroviral therapy (ART) has changed contexts of HIV risk, but the influence on HIV incidence among young women is not clear. We aimed to summarise direct estimates of HIV incidence among adolescent girls and young women since ART and before large investments in targeted prevention for those in sub-Saharan Africa.
METHODS
We did a systematic review and meta-analysis. We searched MEDLINE, Embase, Web of Science, Global Health, and CINAHL for studies reporting HIV incidence data from serological samples collected among females aged 15-24 years in ten countries (Kenya, Lesotho, Malawi, Mozambique, South Africa, Swaziland, Tanzania, Uganda, Zambia, and Zimbabwe) that were selected for DREAMS investment in 2015. We only included articles published in English. Our main outcome was to summarise recent levels and trends in HIV incidence estimates collected between 2005 and 2015, published or received from study authors, by age and sex, and pooled by region.
FINDINGS
51 studies were identified from nine of the ten DREAMS countries; no eligible studies from Lesotho were identified. Directly observed HIV incidence rates were lowest among females aged 13-19 years in Kumi, Uganda (0·38 cases per 100 person-years); and directly observed HIV incidence rates were highest in KwaZulu-Natal, South Africa (7·79 per 100 person-years among females aged 15-19 years, and 8·63 in those aged 20-24 years), among fishing communities in Uganda (12·40 per 100 person-years in females aged 15-19 years and 4·70 in those aged 20-24 years), and among female sex workers aged 18-24 years in South Africa (13·20 per 100 person-years) and Zimbabwe (10·80). In pooled rates from the general population studies, the greatest sex differentials were in the youngest age groups-ie, females aged 15-19 years compared with male peers in both southern African (pooled relative risk 5·94, 95% CI 3·39-10·44) and eastern African countries (3·22, 1·51-6·87), and not significantly different among those aged 25-29 years in either region. Incidence often peaked earlier (during teenage years) among high-risk groups compared with general populations. Since 2005, HIV incidence among adolescent girls and young women declined in Rakai (Uganda) and Manicaland (Zimbabwe), and also declined among female sex workers in Kenya, but not in the highest-risk communities in South Africa and Uganda.
INTERPRETATION
Few sources of direct estimates of HIV incidence exist in high-burden countries and trend analyses with disaggregated data for age and sex are rare but indicate recent declines among adolescent girls and young women. In some of the highest-risk settings, however, little evidence exists to suggest ART availability and other efforts slowed transmission by 2016. Despite wide geographical diversity in absolute levels of incidence in adolescent girls and young women, risk relative to males persisted in all settings, with the greatest sex differentials in the youngest age groups. To end new infections among the growing population of adolescents in sub-Saharan Africa, prevention programmes must address gender inequalities driving excessive risk among adolescent girls.
FUNDING
This work was conducted as part of a planning grant funded by the Bill & Melinda Gates Foundation.
Topics: AIDS Serodiagnosis; Adolescent; Africa; Age Factors; Antiretroviral Therapy, Highly Active; Female; HIV Infections; HIV Seroprevalence; Humans; Incidence; Population; Prevalence; Socioeconomic Factors; Young Adult
PubMed: 31607465
DOI: 10.1016/S2214-109X(19)30410-3 -
Toxicological Research Jul 2019Silver nanoparticles (AgNPs) have been widely used in a variety of applications in innovative development; consequently, people are more exposed to this particle....
Silver nanoparticles (AgNPs) have been widely used in a variety of applications in innovative development; consequently, people are more exposed to this particle. Growing concern about toxicity from AgNP exposure has attracted greater attention, while questions about nanosilver-responsive genes and consequences for human health remain unanswered. By considering early detection and prevention of nanotoxicology at the genetic level, this study aimed to identify 1) changes in gene expression levels that could be potential indicators for AgNP toxicity and 2) morphological phenotypes correlating to toxicity of HepG2 cells. To detect possible nanosilver-responsive genes in xenogenic targeted organs, a comprehensive systematic literature review of changes in gene expression in HepG2 cells after AgNP exposure and method, connection up- and down-regulation expression analysis of microarrays (CU-DREAM), were performed. In addition, cells were extracted and processed for transmission electron microscopy to examine ultrastructural alterations. From the Gene Expression Omnibus (GEO) Series database, we selected genes that were up- and down-regulated in AgNPs, but not up- and down-regulated in silver ion exposed cells, as nanosilver-responsive genes. HepG2 cells in the AgNP-treated group showed distinct ultrastructural alterations. Our results suggested potential representative gene data after AgNPs exposure provide insight into assessment and prediction of toxicity from nanosilver exposure.
PubMed: 31341555
DOI: 10.5487/TR.2019.35.3.257 -
Sleep Medicine Reviews Apr 2019Suicide and self-harm behaviours represent public health concerns, and university students are a particularly high risk group. Identifying modifiable risk factors for...
Suicide and self-harm behaviours represent public health concerns, and university students are a particularly high risk group. Identifying modifiable risk factors for the development and maintenance of suicidal thoughts and behaviours is a research priority, as prevention is crucial. Research examining the relationship between poor sleep and self-harm/suicidality within university students is, for the first time, systematically evaluated, critically appraised, and synthesised. This literature consistently demonstrates that insomnia and nightmares are associated with elevated suicide risk of suicidal thoughts and behaviours within this subpopulation of young adults. However, as findings are predominantly derived from cross-sectional investigations, the directionality of this relationship is not yet clear. While research investigating the psychological processes driving these relationships is in its infancy, preliminary findings suggest that thwarted belongingness, socio-cognitive factors and emotional dysregulation could be partly responsible. Methodological limitations are highlighted and a research agenda suggesting the key directions for future research is proposed. Continued research in this area - employing longitudinal designs, and testing novel theoretically derived hypotheses - will be crucial to the development of suicide prevention and intervention efforts.
Topics: Depression; Dreams; Humans; Risk Factors; Self-Injurious Behavior; Sleep Initiation and Maintenance Disorders; Students; Suicide; Universities; Young Adult
PubMed: 30721844
DOI: 10.1016/j.smrv.2018.12.008 -
The Cochrane Database of Systematic... Apr 2018Crohn's disease is a transmural, relapsing inflammatory condition afflicting the digestive tract. Opioid signalling, long known to affect secretion and motility in the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Crohn's disease is a transmural, relapsing inflammatory condition afflicting the digestive tract. Opioid signalling, long known to affect secretion and motility in the gut, has been implicated in the inflammatory cascade of Crohn's disease. Low dose naltrexone, an opioid antagonist, has garnered interest as a potential therapy.
OBJECTIVES
The primary objective was to evaluate the efficacy and safety of low dose naltrexone for induction of remission in Crohn's disease.
SEARCH METHODS
A systematic search of MEDLINE, Embase, PubMed, CENTRAL, and the Cochrane IBD Group Specialized Register was performed from inception to 15 January 2018 to identify relevant studies. Abstracts from major gastroenterology conferences including Digestive Disease Week and United European Gastroenterology Week and reference lists from retrieved articles were also screened.
SELECTION CRITERIA
Randomized controlled trials of low dose naltrexone (LDN) for treatment of active Crohn's disease were included.
DATA COLLECTION AND ANALYSIS
Data were analyzed on an intention-to-treat basis using Review Manager (RevMan 5.3.5). The primary outcome was induction of clinical remission defined by a Crohn's disease activity index (CDAI) of < 150 or a pediatric Crohn's disease activity index (PCDAI) of < 10. Secondary outcomes included clinical response (70- or 100-point decrease in CDAI from baseline), endoscopic remission or response, quality of life, and adverse events as defined by the included studies. Risk ratios (RR) and 95% confidence intervals (CI) were calculated for dichotomous outcomes. The methodological quality of included studies was evaluated using the Cochrane risk of bias tool. The overall quality of the evidence supporting the primary outcome and selected secondary outcomes was assessed using the GRADE criteria.
MAIN RESULTS
Two studies were identified (46 participants). One study assessed the efficacy and safety of 12 weeks of LDN (4.5 mg/day) treatment compared to placebo in adult patients (N = 34). The other study assessed eight weeks of LDN (0.1 mg/kg, maximum 4.5 mg/day) treatment compared to placebo in pediatric patients (N = 12). The primary purpose of the pediatric study was to assess safety and tolerability. Both studies were rated as having a low risk of bias. The study in adult patients reported that 30% (5/18) of LDN treated patients achieved clinical remission at 12 weeks compared to 18% (3/16) of placebo patients, a difference that was not statistically significant (RR 1.48, 95% CI 0.42 to 5.24). The study in children reported that 25% of LDN treated patients achieved clinical remission (PCDAI < 10) compared to none of the patients in the placebo group, although it was unclear if this result was for the randomized placebo-controlled trial or for the open label extension study. In the adult study 70-point clinical response rates were significantly higher in those treated with LDN than placebo. Eighty-three per cent (15/18) of LDN patients had a 70-point clinical response at week 12 compared to 38% (6/16) of placebo patients (RR 2.22, 95% CI 1.14 to 4.32). The effect of LDN on the proportion of adult patients who achieved a 100-point clinical response was uncertain. Sixty-one per cent (11/18) of LDN patients achieved a 100-point clinical response compared to 31% (5/16) of placebo patients (RR 1.96, 95% CI 0.87 to 4.42). The proportion of patients who achieved endoscopic response (CDEIS decline > 5 from baseline) was significantly higher in the LDN group compared to placebo. Seventy-two per cent (13/18) of LDN patients achieved an endoscopic response compared to 25% (4/16) of placebo patients (RR 2.89; 95% CI 1.18 to 7.08). However, there was no statistically significant difference in the proportion of patients who achieved endoscopic remission. Endoscopic remission (CDEIS < 3) was achieved in 22% (4/18) of the LDN group compared to 0% (0/16) of the placebo group (RR 8.05; 95% CI 0.47 to 138.87). Pooled data from both studies show no statistically significant differences in withdrawals due to adverse events or specific adverse events including sleep disturbance, unusual dreams, headache, decreased appetite, nausea and fatigue. No serious adverse events were reported in either study. GRADE analyses rated the overall quality of the evidence for the primary and secondary outcomes (i.e. clinical remission, clinical response, endoscopic response, and adverse events) as low due to serious imprecision (sparse data).
AUTHORS' CONCLUSIONS
Currently, there is insufficient evidence to allow any firm conclusions regarding the efficacy and safety of LDN used to treat patients with active Crohn's disease. Data from one small study suggests that LDN may provide a benefit in terms of clinical and endoscopic response in adult patients with active Crohn's disease. Data from two small studies suggest that LDN does not increase the rate of specific adverse events relative to placebo. However, these results need to be interpreted with caution as they are based on very small numbers of patients and the overall quality of the evidence was rated as low due to serious imprecision. Further randomized controlled trials are required to assess the efficacy and safety of LDN therapy in active Crohn's disease in both adults and children.
Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Child; Crohn Disease; Humans; Induction Chemotherapy; Intention to Treat Analysis; Naltrexone; Randomized Controlled Trials as Topic
PubMed: 29607497
DOI: 10.1002/14651858.CD010410.pub3